Poster Presentations


ID #16: EVALUATION OF INITIAL PHYSIOPATHOLOGICAL CHANGES IN THE ROTENONE-INDUCED PARKINSONISM MODEL IN RATS

Authors: Alfaete Vieira Oliveira 1; Tyciane de Souza Nascimento 2; Juliete Tavares 2; Jéssica Rabelo Bezerra 1; Mônica de Oliveira Belém 2; Armenio Aguiar dos Santos 2; Geanne Matos de Andrade 2
Filiation: 1 Department of Physiology and Pharmacology; 2 Department of Clinical Medicine


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Key-words Parkinson's disease; neurodegeneration; animal model

Background: Parkinson's disease (PD) affects about 1.6% of the world population over 65 years, being the second most common neurodegenerative disease in the elderly. PD is characterized by loss progression of dopaminergic neurons of the substantia nigra, leading to a severe reduction in dopamine levels, resulting in several motor symptoms and non-motor symptoms. Rotenone is a pesticide that mimics PD symptoms, representing a model of construct criteria. The aim of the present study was to investigate the initial pathophysiological changes, present in the period of onset of premotor symptoms, in the rotenone-induced parkinsonism model.  Design: Wistar rats (220-250g) were used divided into two groups: ROT (received rotenone 2.75mg / kg, i.p. for 7 days) and CTL (received the DMSO vehicle sunflower oil, 1ml / kg i.p. for 7 days), after the period of 7 days the animals were submitted to behavioral tests, analysis of emptying and gastric retention. Later, an analysis of oxidative stress and concentration of monoamines was carried out. The project was approved by the ethics committee of the Federal University of Ceará and has the approval number: 05010819-0.  Results: The results showed that exposure to rotenone for 7 days induces hyposmia observed in the buried pellet test (CTL: 77.30 ± 13.82s; ROT: 134.8 ± 22.16s; p <0.05) and delayed gastric emptying observed in the carbon 13 emptying test in animals exposed to Rotenone (CTL: 1711 ± 78.56 ppm13CO2, ROT: 1306 ± 139.2 ppm13CO2, p <0.05), without inducing deficits engines in vertical and horizontal exploration or average speed in the open field test or in motor coordination in the rotarod test. No oxidative stress was evidenced by the absence of difference in the levels of nitrite in the bulb, striated and midbrain of the experimental groups, as well as there was no significant difference in the assessment of lipid peroxidation were observed in the levels of malondialdehyde in the olfactory bulb striated and midbrain of the experimental groups. There were no significant differences in dopamine levels in the bulb, striated and midbrain. Likewise, no significant differences were found in the levels of norepinephrine in the striatum and bulb and serotonin levels in the striatum.   Conclusions: Rotenone induces non-motor changes in the absence of motor deficits and these changes are due to other mechanisms, unrelated beyond oxidative stress and changes in monoamine levels, as assumed.   



ID #24: Parotid neoplasm in a patient with Wilson Disease (WD)

Authors: José Lopes Tabatinga Neto 1; Jéssica Queiroz de Sousa Sobrinho 1; Francisco de Assis Aquino Gondim 1
Filiation: 1 Universidade Federal do Ceará


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Key-words Wilson Disease; Cancer; Parotid

Background: WD is a genetic disorder that compromises copper metabolism. Clinical manifestations include liver, neurological, psychiatric, musculoskeletal and ophthalmic changes. It is believed that copper toxicity may be related to cancer (CA) induction, due to its angiogenenic. However, the occurrence of CA in WD is rare. Even hepatocarcinome (HCA) and cholangiocarcinome (CCA), more common in WD, are still less frequent than in other patients. Design/Methods: Case report and diagnostic and conduct analysis based on digitally published literature on WD and CA. Clinical Case: AES, 38 years old, male, married, born in Hidrolândia, Ceará. In 2006, she began to experience emotional lability with easy crying, depressive symptoms and a period of aggression towards her wife and children. He had 3 brothers affected by WD, 2 of whom died and a terminal stage. He was diagnosed with WD in 2006, with mobility and speech disorders, Kayser-Fleisher rings and auditory hallucinations. In 2011, it presented changes in bilateral base core compatible with heavy metal accumulation. In 2014, a solid mass suggestive of a parotid tumor was found, with a cytological picture confirming neoplastic cells from carcinoma. In 2016, after radiotherapy, he died. Discussion: Copper is also an extremely important cofactor for the functional activation of many key mediators in the angiogenesis process. When deprived of vascular supply, solid tumors do not exceed 2-3 mm in diameter, which is the theoretical basis for its antiangiogenic treatment. There are currently few reports of CA in WD, the most common involving HCA and CCA. There are publications in the WD literature associated with colon cancer, acute lymphoblastic leukemia, CD5 large B cell intravascular lymphoma and primary breast cancer, although these are rare. Conclusion: After reviewing the literature on patients with WD complicated by cancer and, as far as we know, this is the first report of WD complicated by parotid AC. Therefore, a case report is important for a better understanding of the spectrum of manifestations of WD.



ID #15: The impact of methylmercury on microglia-derived neuroinflammation and neurogenesis

Authors: Beatriz Martins 1; Ricardo Moreira 1; João Pedro Ferreira Novo 1; Ramon Raposo 1; Frederico Pereira 1; Reinaldo Oriá 2; João José Oliveira Malva 1; Carlos Alberto Fontes Ribeiro 1
Filiation: 1 Institute for Clinical and Biomedical Research (iCBR), Center for Innovative Biomedicine and Biotechnology (CIBB), and Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Uni; 2 Laboratory of Tissue Healing, Ontogeny and Nutrition, Department of Morphology, School of Medicine, Institute of Biomedicine, Federal University of Ceará, Fortaleza, Brazil


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Key-words Methylmercury; Microglia; Neurogenesis

Background: Methylmercury (MeHg) is a major environmental concern with noxious consequences for humans. Importantly, MeHg can easily cross the blood-brain barrier and exert adverse effects on the central nervous system (CNS). Its accumulation in several regions of the CNS leads to neurotoxicity and neuroinflammation. Microglia are immunocompetent cells that ensure homeostasis of the CNS. Under pathological conditions, these cells release a cocktail of pro-inflammatory mediators, including cytokines, reactive oxygen species (ROS) and nitric oxide (NO), which contributes to a neuroinflammatory environment that may be harmful to neuronal cells. Microglia also regulate neuronal activity, synaptic plasticity and neurogenesis. In fact, MeHg is known to impair neurodevelopment in the gestation period and in the early years of newborns, leading to severe damage in the brain and functional delays. However, the impacts of MeHg in the neurogenic niches of the adult brain and in the microglia-derived neuroinflammation are widely unexplored.Methods: Immortalized microglial BV-2 cells were incubated with different concentrations of MeHg (0.01 to 10 µM) 1h prior to Lipopolysaccharides (LPS) exposure (0.5 µg/mL). Cell viability, Propidium Iodide (PI) uptake, TNF-α and IL-6 production and release, ROS production, iNOS immunoreactivity, NO release, and immunoreactivity of apoptotic markers (Cleaved Caspase-3 and cytochrome c/mitochondria colocalization) were evaluated. Immortalized neural stem cell line CB152, which can easily mature into adult neurons and astrocytes, was exposed to MeHg (0.01 to 10 µM). Cell viability and immunoreactivity to stemness and differentiation markers were addressed. Results: An impairment in microglial cell viability was observed upon 10 µM MeHg incubation after 6h or 24h both with and without LPS exposure. This is accompanied by an increase in cellular necrosis (PI uptake). Also, 10 µM MeHg impaired the production and release of TNF-α and IL-6 (6h), as well ROS (6h) and NO (24h) triggered by LPS. Lower concentrations of MeHg seems to activate apoptosis (as seen suggested by preliminary evaluation of active caspase 3 and cytochrome C/mitochondria co-localization). Besides, iNOS immunoreactivity was reduced by MeHg in a concentration-dependent manner. A single acute exposure to 10 µM MeHg for 24h reduces the CB152 cell viability and cells do not recover over a period of 21 days. A delay in CB152 maturation is noted by a higher expression of the stemness markers SOX2 and nestin at later timepoints. Moreover, a more disorganized neuronal network is observed in the presence of MeHg. Interestingly, we observed more cells expressing the astroglial marker GFAP in the presence of 1 µM and 0.1 µM of MeHg. Chronic exposure to 1 µM of MeHg reduces the cell viability after 7 days with a more pronounced reduction after 14 days. Conclusions: These findings suggest that acute exposure at higher concentrations of MeHg induce necrotic cell death in microglia and impair the production/release of pro-inflammatory mediators. Importantly, a longer incubation with lower concentrations of MeHg can impact microglia-activated response and potentially trigger apoptotic death. Additionally our preliminary assessment suggests that MeHg may direct neural stem cells to differentiate into astrocytes rather than mature neurons



ID #5: Biomarkers from a glioblastoma progression model in image analysis: proof of concept.

Authors: Francisco Hélder Cavalcante Félix 1; Juvenia Bezerra Fontenele 2
Filiation: 1 Pediatric Cancer Center/ Hospital Infantil Albert Sabin; 2 Department of Pharmacy/ Federal University of Ceará


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Key-words Glioblastoma; Biomarkers; Evolutionary oncology

Background: glioblastoma is a highly malignant tumor, not amenable to conventional or novel treatment modalities, and with dismall prognosis. We used a glioblastoma progression model to derive biomarkers for the evaluation of clinically relevant endpoints in routine imaging.  Design/Methods: Serial contrast-enhanced magnetic resonance images were obtained for a patient with recurrent glioblastoma at predetermined 2-month intervals after disease recurrence (A, B, and C). Chemotherapy was administered after B. Semi-automated elipsoids were marked at enhancing nodular-like sites in each image, and their areas were determined and compared at each time point.   Results: Eighteen individual nodular-like enhancing sites were chosen in the serial images. Total area (tumor burden, TB) was 2183 mm² at A, 4297 mm² at B, and 6132 mm² at C. We defined three subgroups of nodules according to TB behavior. The sensitive (S) group remained stable after chemotherapy (A = 1350, B = 2496, C = 2572), the resistant (R) maintained continuous growth after treatment (A = 304, B = 1332, C = 2353, and the disinhibited (D) diminished before treatment and grew after chemotherapy (A = 529, B = 496, C = 1207).   Conclusions: We could demonstrate the emergence of tumor subclones resistant to chemotherapy, and subclones that were under evolutionary pressure before treatment but reverted to a proliferating resistant phenotype, possibly because chemotherapy aleviated darwinian competition within the tumor microambient. This is predicted by some cancer progression models, and could have implications to cancer therapy.  



ID #10: Doxycycline suppress microglial activation and nitric stress induced by D-amphetamine mania model in mice.

Authors: João Pedro Barros Lima 1; Adriano Maia Chaves Filho 1; Paloma Marinho Jucá 1; Michele Verde-Ramo Soares 1; Tatiana de Queiroz 1; Patrícia de Araújo Rodrigues 1; Danielle Silveira Macêdo 1,2
Filiation: 1 Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine; 2 National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil.


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Key-words Bipolar disorder; mania; doxycycline

Background: Previous studies have shown that the pathophysiology of bipolar disease (BD) is related to neuroinflammation and microglial reactivity. Doxycycline is a second-generation tetracycline which can suppress microglial activation and has a better usage profile than other tetracyclines. This study aims to evaluate the DOXY effects against microglial activation and DOXY’s anti-oxidative properties in a d-amphetamine mania model.Design/Methods: Adult mice received d-amphetamine 2 mg/kg or saline for 14 days. On the 8th to 14th day, they received lithium, DOXY (25 mg/kg), or their combination (lithium+DOXY), N = 16 per group. We collected the hippocampus of each animal to evaluate inflammatory and oxidative  alterations. Western blotting test was performed to quantificate Iba1 (a microglial activation marker) and iNOS, while the nitrite levels were determined by Griess reaction.   Results: D-amphetamine induced an increase in Iba1, iNOS and nitrite levels. Only DOXY alone and DOXY combined with lithium reversed the amphetamine effects in the expression of Iba1 and iNOS. All the treatment groups decreased the high levels of nitrite induced by d-amphetamine. Conclusions: Our work demonstrated that DOXY alone or in combination with lithium can reverse the neurochemical changes induced by a d-amphetamine mania model. So, DOXY is a promising adjunctive drug for bipolar disorder treatment.



ID #13: WORD LEARNING AND MEMORY IN SYNESTHESIA CONDITION

Authors: Elisangela Nogueira Teixeira 1; Brenda Kessia Arruda de Souza 1
Filiation: 1 Programa de Pós-Graduação em Linguística, Universidade Federal do Ceará


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Key-words Synesthesia; Language; Memory

Background: Synesthesia can be defined as a rare, non-pathological neurological condition, in which stimuli from one sensory modality trigger sensations in another modality (Simner, 2007, 2011; Mankin et al., 2016). As an example, synesthetes establish a consistent relationship between colors and months of the year. Here, we investigate the hypothesis that the days-of-the-week and months-of-the-year synesthesias are related to the brain regions that process and store numbers.Methods: We diagnose a group of 13(2,21%)/586 synesthetes, using The Synesthesia Battery (Eagleman et al., 2007) (avaiable at sinestesia.ufc.br). We conducted a Pseudoword Learning Task, with two levels: numerical words (seasons) and concrete words (vehicles). The control and synesthete groups had their memory compared by free, cued and semantic recall tests. Results: We performed a Generalized Linear Mixed Model to study the probability to answer correctly. For free recall, we found a fixed effect for pseudowords (χ2=6.0787,p=0.01) and group (χ2=3.3375,p=0.05), but not for interaction. The probability to remember vehicle's words were lower than season's pseudowords (β=-0.7200,p=0.01). The synesthetes were more able to remember in free (β=0.8455,p=0.05) and semantic recall tests (β=2.3843,p=0.05). Conclusions: Our results suggest that the days and months synesthesias have a numerical conceptual basis, different from others synesthesias. Our methodology with recall tasks can be valuable to further fMRI studies aiming to track bridges between cognitive areas.



ID #23: 1α,25-DIHYDROXYVITAMIN D3 PROTECTS AGAINST NEUROTOXICITY IN A MODEL OF PARKINSON’S DISEASE USING ASTROCYTES CULTURE

Authors: Erlânia Alves de Siqueira 1; Emanuel Paula Magalhães 2; Albert Layo Costa de Assis 1; Emanoel Lucas Pinheiro Xavier 2; Livia Correia Fernandes Paes 2; Nicole Coelho Lopes 2; Tiago Lima Sampaio 2; Ramon Róseo Paula Pessoa Bezerra de Menezes 2; Alice Maria Costa Martins 2; Geanne Matos de Andrade 1; Glauce Socorro de Barros Viana 1
Filiation: 1 Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Ceará, Brazil; 2 Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, Ceará, Brazil


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Key-words Parkinson's disease; Astrocytes; Vitamin D

Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic cells in the nigrostriatal tract. Among the main mechanisms that lead to cell death in this disease, inflammation, apoptosis and reactive oxygen species (ROS) formation are highlighted. Rotenone (ROT) is a neurotoxin known as a common insecticide and it is a valuable tool in in vivo and in vitro models of PD. Evidence indicates that vitamin D (1α,25-dihydroxyvitamin D3 - VitD)  has  receptors in neurons and glial cells of substantia nigra and has a potential to prevent neurodegeneration and cell death. Thus, the present study aims to evaluate the neuroprotective activity of VitD in a model of ROT-induced cytotoxicity in astrocytes cultures.Design/Methods: Cells were pre-treated with VitD (0.1; 0.5 and 1 ng/mL) and after, with ROT (IC50 - 126 nM). The cell viability was evaluated by the MTT assay and flow cytometry assays were performed in order to evaluate ROS production and cell death pathway, labeling with 2',7'-dichlorodihydrofluorescein and 7-AAD/Annexin V, respectively. Experiments were carried out in triplicate and the results expressed as mean ± standard error of the mean. The statistical analysis was performed using the GraphPad Prism 5.0 software, with a one-way ANOVA statistical test, followed by Bonferroni post-test, and p < 0.05 was used as a significance criterion. Results: VitD (0.5 and 1.0 ng/mL)  improved the viability of cells previously treated with ROT (CT: 100 ± 0.01%; ROT: 57.77 ± 1.95%; VitD 0.5: 67.30 ± 3.58%; VitD1: 71.77 ± 0.77%). The treatment with VitD diminished the occurrence of necrotic and apoptotic events (CT: 4.44% ± 0.91%; ROT: 52.74±1.23%; VitD 0.1: 44.35 ± 1.23%; VitD 0.5: 35.48 ± 1.57%; VitD 1: 28.05 ± 1.13%) and decreasing in the production of ROS (CT: 1.010 ± 0.023; ROT: 2,032 ± 0.078; VitD 0.1: 1.806 ± 0.072; VitD 0.5: 1.149 ± 0.034; VitD 1: 1.092±0.043). Conclusions: Treatment with VitD was able to protect astrocytes from the injury caused by ROT, suggesting its cytoprotective role in this preliminary model of PD, requiring further investigation when the participation of VITD in neuroinflammation and other aspects of cytoprotection. Funded by the CNPq and CAPES.



ID #18: Therapeutic process in patients with Frontotemporal Dementia

Authors: Nickolas Souza Silva 1; Larissa Teles de Souza 2
Filiation: 1 Universidade Federal do Ceará; 2 Universidade Federal do Piauí


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Key-words Frontotemporal Dementia; Patient Care Team; Therapeutics

Background: Frontotemporal dementia (FTD) is a neurodegenerative condition that onset from the 5th decade, presenting varied symptoms and making a differential diagnosis with Alzheimer's dementia. There is no specific therapeutic literature for FTD, and non-pharmacological therapies (NPT) can be applied, such as linguistic, physiotherapy and psychological therapies, being applied both to the patient, to his family and caregivers. The aim of this study is to discuss multidisciplinary treatments for patients with FTD.Design/Methods: Literature review using SciELO, Lilacs and PubMed platforms with the descriptors "Frontotemporal Dementia" and "Multidisciplinarity". The exclusion criteria were articles published outside the period 2010 to 2020 and articles that did not discuss NPT. Results: NPT should be based on three fields: patient, caregiver and both. Physical education alters the routine environment and reduces sleep disorders due to dysfunctions in the circadian cycle. Music therapy reduces anxiety attacks and facilitates care for family and caregivers. Family-assisted socialization associated with psychological counseling should be encouraged so that social behavior is better suited to common standards. Speech therapy interventions provide clinical improvements to the patient and assist in communication and decision making. Caregivers should be assisted to prevent Burnout Syndrome, with psychological help and continued health updates with specialists. Conclusions: FTD patients and their family members/caregivers suffer great impacts due to the behavioral and neuropsychiatric complications of the disease. The personalized NPT approach in FTD assists the patient and his family members/caregivers, providing a field of conversation about symptoms among these individuals.



ID #22: Protective effect of chlorogenic acid on memory deficits in sporadic Alzheimer's disease model induced by streptozotocin in mice.

Authors: Jéssica Rabelo Bezerra 1,3; Antônia Emanuelle Sousa Silva 3; Maiara Virgínia Viana Maia 3; Tyciane de Souza Nascimento 2,3; Juliete Tavares 2,3; Geanne Matos de Andrade 1,2,3
Filiation: 1 Department of Physiology and Pharmacology, Federal University of Ceará; 2 Department of Clinical Medicine, Federal University of Ceará; 3 Drug Research and Development Center (NPDM), Federal University of Ceará


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Key-words Sporadic Alzheimer Disease; Chlorogenic acid; Memory

 Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid and intracellular neurofibrillary plaques in cortical areas, leading to progressive memory loss and cognitive impairment, being a more common form of dementia. Intracerebroventricular (ICV) injections of streptozotocin (STZ) has been used as an experimental model of sporadic AD in rodents because they cause impairment in insulin signaling, oxidative stress, neuroinflammation and neurogenesis dysfunctions, which result in cognitive decline that are characteristic of AD. Chlorogenic acid (CAG) is one of main compounds in coffee, which exerts antioxidant, anti-inflammatory, neuroprotective activities and modulation of glucose metabolism. The aim of this study was to investigate the effects of CAG on memory deficits in mice submitted to an experimental model of AD induced by the stereotaxic injection of STZ in mice.       Design/Methods: Male Swiss mice (25-35g, n = 40) received bilateral ICV injections of STZ (3 mg/kg/day), dissolved in artificial cerebrospinal fluid, the injections were repeated after two days. The animals were treated with CAG (5 mg/kg, orally) or vehicle (water) during for 26 days, starting 2 h after surgery, after treatment the animals were submitted to behavioral tests. Blood samples were collected for analysis of glucose levels, before and after surgeries. All procedures in this study were approved by the ethics committee on animal experimentation of the Federal University of Ceará (protocol number: nº 8904290319).       Results: The results showed that there was no significant change in glucose levels before and after surgeries. No differences in the locomotor activity or anxiety were observed between groups. The treatment with CAG improved significantly aversive (aCSF: 286.8 ± 13.18;  STZ: 112.6 ± 38.83; STZ + CAG: 241.4 ± 29.21, P < 0.01) and object recognition memory (1 hour: aCSF: 0.17 ± 0.05; STZ: -0.01 ± 0.04, STZ + CAG: 0.15 ± 0.04, P < 0.05; 24 hours: aCSF: 0.36 ± 0.03; STZ: 0.15  ±  0.03; STZ + CAG: 0.29 ± 0.05, P < 0.05)  deficits caused by STZ. No differences in working memory was observed between the groups.   Conclusions: These results suggest the neuroprotective activity of chlorogenic acid against memory deficits, by a mechanism that needs investigation, highlighting its therapeutic potential for the treatment of sporadic AD.



ID #29: Nutraceutical with mixtures of omega 3, 6 and 9 oils attenuate oxidative stress and behavioral alterations of autism spectrum disorder induced by valproic acid in an experimental model

Authors: Luciana Fujiwara Aguiar Ribeiro 1; Mateus Aragão Esmeraldo 1; Silvia Flávia Alves de Freitas 1; Cristiana Libardi Miranda Furtado 1; Fábio Miyajima 3; Gislei Frota Aragão 2; Mirna Marques Bezerra Brayner 1; Lissiana Magna Vasconcelos Aguiar 1; Paulo Roberto Leitão de Vasconcelos 2
Filiation: 1 Federal University of Ceará - Campus Sobral; 2 Federal University of Ceará - Campus Fortaleza; 3 Federal University of São Paulo


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Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with abnormalities in the metabolism and behavioral functions. Great interest has been given to the potential role of polyunsaturated fatty acids in the pathogenesis of neurodevelopmental disorders and in its treatment. Objective: Evaluate the alterations in behavior and oxidative stress in rats treated with three different mixtures of Omega-3, 6 and 9 oils (Mix-1, Mix-2 and Mix-3). Design/Methods: Male and female Wistar rats were submitted to ASD induction with a subcutaneous single dose of valproic acid (VPA) on the 14th day after birth, being treated with oil mixes for 25 daysOpen field, tail immersion, swimming performance and rotarod tests were performedHippocampus, prefrontal cortex, amygdalae and cerebellum were used to evaluate lipid peroxidation, nitrite concentration and glutathione reductase levels. Results: Animals treated had faster reaction time in the tail immersion test when compared to VPA-only group. The swimming performance was significantly worse in VPA-only group when compared to sham group and was higher in treated groups when compared to VPA-only. A higher oxidative stress was noted in the hippocampus and prefrontal cortex in males, being lower in animals treated with Mix-2 and Mix-3 in the AVP groups. No antioxidant response from GSH was observed. Nitric oxide was elevated in the cerebellum of male VPA groups, being lower in treated groups. Conclusions: Our findings suggest that the mixture of oils rich in omega-3 was favorable to the reduction of oxidative stress (Mix-2 and Mix-3) and behavioral alterations of ASD in rats.



ID #30: (-)- α-Bisabolol ameliorates chronic unpredictable mild stress-induced depressive-like behavior in mice

Authors: Manoela de Oliveira Rebouças 1; Francisca Cléa Florenço de Sousa 2; Larice de Carvalho Vale 2; Daniel Moreira Alves da Silva 2; José Tiago Valentim 2; Natália Ferreira de Oliveira 2; Danúsio Pinheiro Sartori 2; Andressa alexandre de oliveira 2; Alyne Mara Rodrigues de Carvalho 2; Raquell de Castro Chaves 2; Dilailson Carlos Costa Júnior 2; Layla Alves Araújo 2; Dulce Maria Nascimento Coelho 2; João Victor Souza Oliveira 2; Iardja Stéfane Lopes 2
Filiation: 1 Universidade Federal do Ceará ; 2 Universidade Federal do Ceará


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The depressive disorder, a disabling disease that affects around 300 million people worldwide, is characterized by symptoms of depressed mood and anhedonia. The cause isn’t completely understood, however, some hypotheses, such as the neuroendocrine related to stress response, tries to justify the etiology. Nowadays, the chronic unpredictable mild stress (CUMS) model has been applied to induce depressive-like behavior in animals through environmental stressors. The usual strategy for treating depression requires a pharmacotherapy with antidepressants that usually involves a long latency period, treatment resistance and high adverse effects incidence. Thus, it is interesting to investigate new compounds with antidepressant potential. The (-)-α-bisabolol (BIS) is a sesquiterpene alcohol, which has a lipophilic character and biological activities such as neuroprotection. The aim of the present study was to evaluate the antidepressant effect of (-)-α-bisabolol in mice submitted to CUMS model. C57BL/6 male mice were divided in six groups in which animals, except for the control groups, were exposed to a 28 days experimental protocol that consists of exposure of random environmental stressors. On the 15th day forward, all the experimental groups received: saline (NaCl 0.9%, p.o), (-)-α-bisabolol (50 mg/kg, p.o), or Fluoxetine (10 mg/kg, p.o). At the end of the treatment protocol, the animals were submitted to behavioral tests: open field, forced swimming, tail suspension, sucrose preference, hole board and elevated plus maze. After 60 minutes, the animals were euthanized by decapitation, and the brain areas (hippocampus and prefrontal cortex) were dissected to investigate the effect of BIS regarding oxidative stress parameters, such as thiobarbituric acid reactive substance (TBARS) levels, nitrite/nitrate and reduced glutathione (GSH) content. The behavioral results showed that (-)-α-bisabolol administration for 14 days exhibited an antidepressant and anxiolytic effect, without altering locomotor activity, thus, showing no relaxing or psychostimulant action. In addition, it demonstrated an antioxidant effect reversing the CUMS-induced oxidative imbalance, especially on lipid peroxidation in the hippocampus. These unique data showed, for the first time, that (-)-α-bisabolol demonstrated an antidepressant and anxiolytic effect, and is promising for a therapeutic alternative for depressive disorders.



ID #32: The P2x7 receptor antagonist Brilliant Blue G prevents motor and non-motor déficits in a model of parkinsonism induced by rotenone through the control of neurodegeneration and microgliosis

Authors: Tyciane de Souza Nascimento 1; Jessica Rabelo Bezerra 2; Alfaete Vieira Oliveira 2; Marta Regina Santos do Carmo 2; Francisco Arnaldo Viana 2; Geanne Matos de Andrade 2
Filiation: 1 Department of Clinical Medicine/Federal University of Ceará; 2 Physiology and Pharmacology/Federal University of Ceará


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Key-words Parkinson's Disease; Purines; p2x7 receptors

Background:  Parkinson's disease (PD) affects about 1.6% of the world's population over 65 years old. PD is characterized by the progressive loss of dopaminergic neurons of the substantia nigra, leading to a severe reduction of dopamine levels in association of neuroinflammation, which results in several motor and nonmotor symptoms. Rotenone is a pesticide that mimics PD symptoms and pathophysiology, representing a model of construct criteria. Since the ATP released from damaged cells exerts direct deleterious effects on neurons, acting through P2X7 receptors and previous studies have shown a neuroprotective effect of P2X7 receptor antagonism, by the administration of BBG, in hemiparkinsonism models, the present study aimed to investigate the effects antagonism of P2X7 receptors by the Brilliant Blue G on motor and non-motor deficits and neuronal damage induced by rotenone in rats.Design/Methods: Wistar rats were divided into four groups: VHC (receiving vehicle of rotenone: DMSO + sunflower oil, i.p for 21 days and vehicle of BBG: saline solution, i.p. for 15 days ), VHC+BBG (receiving vehicle of rotenone, i.p for 21 days and BBG 50 mg/kg i.p for 15 days ), ROT (receiving rotenone 2.75 mg/kg, i.p. for 21 days and vehicle of BBG) and BBG (receiving rotenone 2.75 mg/kg, i.p. for 21 days and BBG 50 mg/kg i.p for 15 days). Concomitant with the administration, animals were submitted to tests to assess motor and non-motor deficits at 7, 14 and 21 days. At the end of protocol animals were euthanized to performing histopathological analysis. All procedures in this study were approved by the ethics committee on animal experimentation of the Federal University of Ceará (protocol number: 9680310818). Results: The results showed that rotenone induced deficit in the detection of volatile odors after 7 days of administration that can be used as starting point to treatment and the BBG prevent the rotenone induced deficit of horizontal and vertical exploration and average speed in the open field test, improved the deficit of motor coordination in the rotarod test, prevented the depressive like behavior in the sucrose preference test and improved the work memory impairment in the y-maze test.BBG also protected the animals exposed to rotenone from the dopaminergic neurodegeneration in the striatum and substantia nigra and prevented microgliosis in the striatum. Conclusions: These results showed that the blocked of the p2x7 receptors by the antagonist Brilliant Blue G can prevent motor and non-motor deficits through the control of neurodegeneration and microgliosis. Funded by FUNCAP-Brazil and Capes-Brazil.



ID #33: Effect of red propolis hydroalcoholic extract on behavioral changes and IL-1β levels in the hippocampus of mice submitted to the pentylenetetrazole-induced seizure model.

Authors: Joao Victor Souza Oliveira 1; Daniel Moreira Alves da Silva 1; Michele Albuquerque Jales de Carvalho 1; Manoela de Oliveira Rebouças 1; Dulce Maria Nascimento Coelho 1; Talita Matias Barbosa Cavalcante 1; Leonardo Peixoto Fernandes 1; Klistenes Alves de Lima 1; Alana Gomes de Souza 1; Marta Maria de França Fonteles 2
Filiation: 1 Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade federal do Ceará; 2 Departamento de Farmácia, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará


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Key-words Red propolis hydroalcoholic extract; Epilepsy; Neuroinflammation

Background: Epilepsy is a neurological disorder that affects approximately 1% of the world population and can lead to cognitive deficit, neuronal dysfunction, behavioral and social problems. This disease is capable of generating recurrent seizures, where currently 30 to 40% of all patients do not respond to any type of therapy. Previous studies have shown that neuroinflammatory processes are related to drug-resistant epilepsy. Red propolis from hives located on the stems of mangrove shrubs located in Northeastern Brazil is rich in flavonoids with proven anti-inflammatory activities. In addition, previous research has shown neuroprotective activity of the hydroalcoholic extract of red propolis (EHPV). The objective of this work was to study the neuroprotective effect of EHPV in mice submitted to the convulsion model induced by pentylenetetrazole (PTZ).Design/Methods: Male Swiss mice were treated with EHPV at doses of 10 and 100 mg / kg orally for 7 days. Half an hour after the last dose of EHPV, seizures were induced in the animals by administering PTZ 85 mg / kg intraperitoneally. In the behavioral analysis, the parameters were evaluated: first seizure latency and death latency. After the tests, the hippocampus of the animals was dissected to determine the IL-1β levels. Results: In the behavioral evaluation, the results showed that the EHPV was able to significantly increase the first seizure latency and the death latency of the mice in the EHPV10 + PTZ85 and EHPV100 + PTZ 85 groups, when compared to the animals in the PTZ85 group. Latency of first seizure (EHPV10 + PTZ85: 102.8 ± 3.604, EHPV100 + PTZ85: 95.67 ± 6.726 vs PTZ85: 60.83 ± 4.715, P <0.001); Death latency (EHPV10 + PTZ85: 449.5 ± 20.75 vs PTZ85: 195.3 ± 26.03, P <0.01; EHPV100 + PTZ85: 527.3 ± 53.44 vs PTZ85: 195.3 ± 26.03, P <0.001). In the evaluation of anti-inflammatory activity, EHPV decreased considerably the levels of IL-1β in the hippocampus of animals in groups EHPV10 + PTZ85 and EHPV100 + PTZ 85 when compared to animals in group PTZ85. (EHPV10 + PTZ85: 258.3 ± 24.67 vs PTZ85: 550.4 ± 66.12; EHPV100 + PTZ85: 276.8 ± 25.33 vs PTZ85: 550.4 ± 66.12, P <0.001). Conclusions: This work demonstrated that EHPV, in the two doses tested, was able to reduce the convulsive process and the levels of IL-1β in the hippocampus of mice submitted to the PTZ-induced seizure model. This demonstrates that the neuroptotective action of EPHV is possibly related to its potent anti-inflammatory activity, suggesting that Brazilian red propolis may be a possible adjuvant agent in the treatment of drug-refractory epilepsy and other neurological diseases that have their pathophysiological bases in the process inflammatory.



ID #34: Cyclooxygenase-2 inhibitors protect lipopolysaccharide-challenged microglial cells from nitrosative stress

Authors: Daniel Moreira Alves da Silva 1; João Victor Souza Oliveira 1; Dulce Maria Nascimento Coelho 1; Manoela de Oliveira Rebouças 1; José Tiago Valentim 1; Larice de Carvalho Vale 1; Raquell de Castro Chaves 1; Layla Alves Araujo 1; Dilailson Carlos Costa Júnior 1; Erlânia Alves de Siqueira 1; Luzia Kalyne Almeida Moreira Leal 2; Francisca Cléa Florenço de Sousa 1
Filiation: 1 Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará; 2 Department of Pharmacy, Faculty of Pharmacy, Odontology and Nursing, Federal University of Ceará


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Open Poster

Key-words Neuroinflammation; Lipopolysaccharide; Cyclooxygenase-2

Background: Recent evidence suggests that the pathophysiology of various neuropsychiatric diseases, such as depression, anxiety and schizophrenia, may be associated with inflammation. Microglial activation is a very common phenomenon in these diseases. Microglial cells can be activated by exposure to sterile stressors or products of microorganisms such as Escherichia coli lipopolysaccharide (LPS). Inflammation triggers the formation of several harmful mediators, such as nitric oxide (NO). Celecoxib (CLX) and Etoricoxib (ETR) are drugs widely used to relieve inflammation. They are inhibitors of cyclooxygenase 2 (COX-2), an enzyme that is present in the sites of inflammation being expressed by cells involved in the inflammatory process, such as macrophages and found in other tissues and organs, such as in the brain. The objective of this work was to evaluate the effects of COX-2 inhibitors on nitrosative stress through secondary culture of BV2 microglia.Design / Methods: The BV2 cell line was grown at a density of 1 x 105 cells in appropriate medium and maintained at 37 ° C and under a 5% CO2 atmosphere. Drug cytotoxicity was assessed using the MTT test. For this purpose, the cells were exposed to increasing concentrations of ETR (0.75; 1.5; 3; 6; 12 and 24 µM), CLX (0.625; 1.25; 2.5; 5; 10 and 20 µM) or vehicle (0.1% DMSO, control group), and after 24 hours MTT was added at a concentration of 0.5 mg / mL / well. The determination of NO occurred in an indirect way, through the measurement of nitrite/nitrate with the aid of the Griess reagent. CLX and ETR were added to microglial cell culture in increasing concentrations and after one hour, LPS medium (0.5 µg / mL) was added 24 hours after the addition of LPS, 100 µL of each sample was collected for analysis. Absorbance was measured using a plate reader at 560 nm. Results: ETR (0.75 - 24 M) did not show any significant cytotoxic effect in relation to the control group, however CLX only in the highest concentration - 20 M (74.37% cells viable) significantly reduced the percentage of viable cells in relation to the control group, corresponding to a reduction of the order of 25.63%. The treatment of cells with ETR did not significantly interfere with the NO concentration in relation to the control group. On the other hand, the treatment of cells with CLX (10 and 20 µM) significantly reduced the NO concentration (NO: 10.37 ± 1.096 and 6.801 ± 0.877, respectively) compared to the control group (NO: 13.34 ± 1 , 30), with inhibitions of 22.2% and 49%, respectively. Conclusions: CLX protects microglial cells from nitrosative stress caused by exposure to LPS. These data provide evidence that may suggest the use of COX-2 inhibitors as supporting agents in the treatment of neuropsychiatric diseases that have their pathophysiological bases in inflammation.



ID #25: Long-term administration of Omeprazole and its effects in Central Nervous System: A study of behavior changes in mice

Authors: Dulce Maria Nascimento Coelho 1; Manoela de Oliveira Rebouças 1; Dilailson Carlos Costa Junior 2; Daniel Moreira Alves da Silva 1; Ana Carolina Benicio Alves 4; Andressa Alexandre Oliveira 1; João Victor Souza Oliveira 1; Larice de Carvalho Vale 1; José Tiago Valentim 1; Iardja Stefane Lopes Sales 1; Layla Alves Araújo 2; Raquell de Castro Chaves 1; Lucas Antonio Duarte Nicolau 3; Francisca Cléa Florenço de Sousa 1
Filiation: 1 Programa de Pós-Graduação em Farmacologia/Universidade Federal do Ceará; 2 Faculdade de Farmácia/Universidade Federal do Ceará; 3 Faculdade de Medicina da Universidade Federal do Piauí/Universidade Federal do Delta do Parnaíba; 4 Joint Master in Neuroscience/University of Strasbourg


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Open Poster

Key-words Omeprazole; Behavioral changes; CNS

Background: Proton Pump Inhibitors (PPI) are widely used to treat stomach acid secretion dysfunctions. Omeprazole was the first discovered PPI and still is one of the most prescribed drugs worldwide, however, it is commonly administered  without prescription. In the last decade, the chronic use of omeprazole has been related to the development of neurological disorders, such as depression and dementia. The underlying mechanisms for that still remain uncertain. The aim of this study is to use behavioral testing as a sensitive and comprehensive tool to investigate the central effects of omeprazole long-term use in a mice model.Design/Methods: Young male adult mice C57BL/6J weighted 20-30g were divided into two groups (n=8-10/group): OME (omeprazole: 8 mg/kg) and Sham (vehicle sodium bicarbonate 8.4%), and both solutions were administered per os for 28 days. After 24 hours of the last administration, the following behavioral tests were conducted: rotarod (locomotory assessment), forced swim test (depressive-like comportment), Y-maze, recognition of object and passive avoidance test (memory and cognition), and elevated plus maze test (anxiety-like behavior). Statistical analysis was held by using Student’s T-test. Results: The rotarod test showed no significant difference between the groups (Sham 0.2 ± 0.13; OME 0.3 ± 0.15, p>0.05). In the forced swimming test, the group OME had a decrease on the immobilization time (Sham 77.11 ± 7.35; OME 57.61 ± 5.88, p<0.05) and an increase on the time of climbing  in comparison with the group Sham (Sham 4.55 ± 0,86; OME 18.60 ± 4,58, p<0.001). In the Y maze, the group OME, when compared to Sham, presented an increase in percentage of the correct sequences (Sham 57.90 ± 1.46 OME 70,23 ± 2.36) and the recognition object test, the group OME in contrast to the Sham, presented a decrease in the time spent on the new object (SHAM 5.81 ± 0.66 OME 3.81 ± 0.61, p<0.05). In the plus maze test, the time of permanence (Sham 21.55 ± 3.44; OME 30.05 ± 7.31, p>0,05) and the number of entries (Sham 43.29 ± 3.96; OME 47.14 ± 2.33, p>0,05) in the open arms did not show significant difference between the groups. In the passive avoidance test, the time of latency did not show significant difference between the groups (Sham 227 ± 30.26; OME 221.8 ± 39.57, p>0,05). Conclusions: The long-term administration of omeprazole in mice caused alterations in the depressive, memory and cognition behavioral tests. The drug did not cause a depressive-like behavior and also did not cause changes in the locomotor activity and in the anxiety-like behavior. In addition, caused an improvement on the working memory as well as an impairment on the recognition memory were observed. These results are preliminary and other experiments are being conducted to better understand these central effects.



ID #35: Structural Analysis of a SINE-VNTR-Alu retrotransposon polymorphism Associated with Disease Progression in the PPMI cohort.

Authors: Luke Dolz Marney 1; Llinos Haf Jones 1; Abigail L Pfaff 2,3; Sulev Koks 2,3; Vivien J Bubb 1; John P Quinn 1
Filiation: 1 University of Liverpool; 2 Murdoch University; 3 Perron Institute


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Open Poster

Key-words Retrotransposon; Parkinson's Disease; Neurodenegeration

Background: The underlying genetic components of Parkinson’s disease (PD) have not been well elucidated. Here we present a bioinformatic analysis of the potential functional consequences of a SINE-VINTR-Alu (SVA) retrotransposon insertion polymorphism (absent or present in the genome) whose genotype has been previously associated with DaTScan count density ratios (caudate/putamen) and differential gene expression in 429 PD patients from the Parkinson’s Progression Markers Initiative (PPMI) cohort.  PPMI host an array of clinical and genomic data for each individual which allows us to align specific molecular data to progression of the disease.  Design/Methods: The analysis was based on supplementary data provided by Pfaff et al (in press), correlated with genomics data hosted by the University of California Santa Cruz Genomics Institute (UCSC) Genome browser. Results: The SVA polymorphism, 2003bp in length, was identified ~10kb upstream of the transcriptional start site of the RAD23B gene. This gene, involved in DNA repair, has previously been associated with cancer and neurodegeneration progression. We have identified potential mechanisms for this polymorphism to modify multiple transcriptional regulatory domains at this locus by its interaction directly or in combination with other predicted and characterised regulatory domains.  These models are proposed based on existing genomic information on the UCSC browser including, GWAS data, epigenetic marks and RNA expression data. Conclusions: This SVA polymorphism may contribute to PD progression via modulation of gene expression in response to tissue specific and stimulus inducible cellular challenges.   Funding: Wellcome Trust (UK), Medical Research Council UK, Motor Neurone Disease Association (UK) and Andrzej Wlodarski Memorial Research Fund



ID #36: Altered hippocampal amino acid levels in two models of methylmercury intoxication in adult and young C57BL6J mice

Authors: Daniel Vieira Pinto 1; Juan de Sá Caminha Roriz 1; Ronaldo Pereira Dias 1; Geanne Matos Andrade 5; Ramon da Silva Raposo 4,6; Maria Elena Crespo-Lopez 3; Jacqueline Isaura Alvarez Leite 2; João Oliveira Malva 6; Reinaldo Barreto Oriá 1
Filiation: 1 Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceará; 2 Laboratory of Atherosclerosis and Nutritional Biochemistry, Department of Biochemistry and Immunology, ICB, Federal University of Minas Gerais; 3 Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará; 4 Experimental Biology Core, University of Fortaleza; 5 Laboratory of Neuroscience and Behavior, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará; 6 Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra


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Open Poster

Key-words Methylmercury; Glutamate; GABA

Background: Methylmercury (MeHg)-intoxication has a well-recognized neurotoxic action to the brain, however, the role of this organometal on hippocampal neurotransmitters has not been well-explored in animal models, especially regarding different tested doses and age.Design/Methods: In this study, a dose of 20mg of MeHg/L in drinking water was administered for 21 days to young mice (41 days-old) and a dose of 2mg of MeHg/L in  drinking water was given for 30 days to adult C57BL6J mice (61 days-old).  Hippocampal samples were harvested and snap-frozen to assess levels of glutamate (GLU), gamma-amino butyric acid (GABA), glycine, taurine, and tyrosine by high-performance liquid chromatography (HPLC), following MeHg chronic intoxication. In addition, we evaluated hippocampal levels of malondialdehyde (MDA) to address oxidative stress. Hippocampal myeloperoxidase (MPO) levels were analyzed to assess MPO-related inflammation. Results: In the model with young mice increased levels of GLU (p=0.003), GABA (p=0.002), and taurine (p=0.04) were found compared to unchallenged controls. In the model with adult mice, there was an increase of GABA (p= 0.01), glycine (p<0.0001), and a reduction in taurine (p=0.003) levels. In both models, significantly higher MPO and MDA levels were seen (p<0.05) compared to the respective unchallenged controls, confirming that MeHg intoxication increases MPO-related inflammation and oxidative stress in the hippocampus. Conclusions: Altogether our findings suggest that MeHg-intoxication affects levels of hippocampal neurotransmitters  and also leads to increased inflammation and oxidative stress in both adult and young mice and in low-grade and high-grade MeHg-intoxication. More studies are warranted to dissect in depth underlying mechanisms and related signaling pathways.



ID #8: Docosanoids and elovanoids from omega-3 fatty acids are a novel class of homeostatic lipid mediators that protect brain after experimental stroke

Authors: Ludmila Belayev 1; Andre Obenaus 1,2; Madigan Reid 1; Larissa Khoutorova 1; Shawn Marcell 1; Pranab Mukherjee 1; Neehar Desai 1; Cassia Roque 3; Raul Freitas 3; Bohyung Park 1; Bookyoo Jun 1; Reinaldo Oriá 3; Nicos Petasis 4; Nicolas Bazan 1
Filiation: 1 LSUHSC; 2 University California Irvine; 3 Federal University of Ceara; 4 University of Southern California


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Open Poster

Key-words neuroprotection; MRI; cerebral ischemia

     Background: This study focuses on the neuroprotective bioactivity of docosanoids (DOC) and elovanoids (ELV), which are derivatives from very long-chain polyunsaturated fatty acids (VLC-PUFAs,n-3). The following DOC mediators: Neuroprotectin D1 (NPD1), Resolvin D1 (RvD1), and ELV (C-32:6 or C-34:6) were investigated in middle cerebral artery occlusion (MCAo) in rat.       Design/Methods: Male SD rats underwent 2h of MCAo. Behavior was evaluated on days 1, 3, and 7. Series 1: ELV-N32 and ELV-N34 administered ICV at 3 h after stroke. Series 2: NPD1, RvD1 or NPD1 + RvD1 was administered IV at 3h after MCAo. Series 2: C-32:6 or C-34:6 or vehicle were administered at 1, 24, 48h after 2h of MCAo by intranasal delivery. Ex vivo imaging of the brains was conducted on day 7, followed by immunohistochemistry.       Results: ELV treatments improved behavior during the 7-day survival period. Ischemic core and penumbra volumes were reduced by ELV-N32 and N34 compared to the CSF-treated group (by 60-90%). Treatments with NPD1 and RvD1 alone improved behavior (by 35% and 31%) and combinatory treatment with NPD1+ RvD1 (by 40%) compared to the vehicle group. Intranasal delivery of C-32:6 or C-34:6 significantly improved neurological score and reduced total lesion, ischemic core, and penumbra volumes.       Conclusions: Administration of ELV and DOC provides high-grade neurobehavioral recovery, decreases ischemic volumes, as well as attenuates cellular damage, blood vessel integrity, and BBB disruption.            



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