La respiration des prématurés est marquée par des apnées à l'origine d'épisodes d'hypoxie cérébrale répétés. Les effets physiopathologiques des apnées sur le développement sont difficiles à étudier chez l'enfant. Nous avons étudié ces effets chez le souriceau nouveau-né, qui présente une immaturité cérébrale similaire à celle des prématurés humains. Notre objectif était d'étudier l'effet de l'hypoxie intermittente sur développement chez des souriceaux nouveau-nés. Nous avons étudié des souriceaux sains ou porteurs de lésions cérébrales excitotoxiques similaires à celles des prématurés humains. Notre hypothèse était que l'hypoxie intermittente modérée pouvait exercer des effets neuroprotecteurs sur le développement et les lésions cérébrales. Nous avons développé des méthodes d'évaluation cognitive du souriceau, et montré que les lésions cérébrales excitotoxiques provoquent des troubles cognitifs qui peuvent être évités grâce à des traitements neuroprotecteurs. L'hypoxie intermittente modérée (6 heures par jour, 20 épisodes/heure) protège les souriceaux des effets délétères de la séparation maternelle sur la mémoire, active la synthèse de facteurs trophiques BDNF et de VEGF et la neurogenèse dans l'hippocampe, et réduit la taille des lésions cérébrales. Le souriceau est donc un bon modèle des troubles du développement et permet d'étudier l'efficacité des traitements neuroprotecteurs. Les apnées du prématuré pourraient exercer un effet protecteur sur le développement cérébral. La stimulation de la synthèse de BDNF et VEGF pourrait constituer une stratégie thérapeutique pour prévenir les troubles du développement des prématurés / Preterm infant's breathing pattern is characterized by apneas associated with repeated episodes of brain hypoxia. Pathophysiological effects of apneas on development are difficult to investigate in newborn infants. We have studied these effects in newborn mice, the immaturity of which is similar to human preterm's immaturity. We have developed methods for cognitive assessment of newborn mice, and we have shown that excitotoxic brain lesions caused cognitive disorders. These disorders were prevented by neuroprotective treatments. Moderate intermittent hypoxia (6 hrs/day, 20 events/hour) protected newborn mice against adverse effects of maternal separation on memory, activated the synthesis of trophic factors, BDNF and VEGF, increased neurogenesis in the hippocampus, and reduced brain lesion size. Newborn mice are therefore a valid model of neurodevelopmental disorders and they may be used to assess the efficacy of neuroprotective treatments. Apneas of prematurity may exert a neuroprotective effects of brain development. The stimulation of synthesis of neurotrophic factors may provide a new therapeutic strategy to prevent neurodevelopmental disorders in preterm infants

<p>It is commonly accepted that aerobic exercise increases hippocampal neurogenesis, learning and memory, as well as stress resiliency. However, human populations are widely variable in their inherent aerobic fitness as well as their capacity to show increased aerobic fitness following a period of regimented exercise. It is unclear whether these inherent or acquired components of aerobic fitness play a role in neurocognition. To isolate the potential role of inherent aerobic fitness, we exploited a rat model of high (HCR) and low (LCR) inherent aerobic capacity for running. At a baseline, HCR rats have two- to three-fold higher aerobic capacity than LCR rats. We found that HCR rats also had two- to three- fold more young neurons in the hippocampus than LCR rats as well as rats from the heterogeneous founder population. We then asked whether this enhanced neurogenesis translates to enhanced hippocampal cognition, as is typically seen in exercise-trained animals. Compared to LCR rats, HCR rats performed with high accuracy on tasks designed to test neurogenesis-dependent pattern separation ability by examining investigatory behavior between very similar objects or locations. To investigate whether an aerobic response to exercise is required for exercise-induced changes in neurogenesis and cognition, we utilized a rat model of high (HRT) and low (LRT) aerobic response to treadmill training. At a baseline, HRT and LRT rats have comparable aerobic capacity as measured by a standard treadmill fit test, yet after a standardized training regimen, HRT but not LRT rats robustly increase their aerobic capacity for running. We found that sedentary LRT and HRT rats had equivalent levels of hippocampal neurogenesis, but only HRT rats had an elevation in the number of young neurons in the hippocampus following training, which was positively correlated with accuracy on pattern separation tasks. Taken together, these data suggest that a significant elevation in aerobic capacity is necessary for exercise-induced hippocampal neurogenesis and hippocampal neurogenesis-dependent learning and memory. To investigate the potential for high aerobic capacity to be neuroprotective, doxorubicin chemotherapy was administered to LCR and HCR rats. While doxorubicin induces a progressive decrease in aerobic capacity as well as neurogenesis, HCR rats remain at higher levels on those measures compared to even saline-treated LCR rats. HCR and LCR rats that received exercise training throughout doxorubicin treatment demonstrated positive effects of exercise on aerobic capacity and neurogenesis, regardless of inherent aerobic capacity. Overall, these findings demonstrate that inherent and acquired components of aerobic fitness play a crucial role not only in the cardiorespiratory system but also the fitness of the brain.</p> / Dissertation

Traumatic brain injury (TBI) is a devastating health problem based on its high incidence, economic burden, and lack of effective pharmacological treatment. Individuals who suffer an injury often experience lifelong disability. TBI results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components, membrane receptors, and cytosolic proteins, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains. A comprehensive analysis using two separate calpastatin transgenic mouse lines was performed to test the hypothesis that calpastatin overexpression will reduce posttraumatic calpain activity affording neuroprotection and behavioral efficacy. Increased calpastatin expression was achieved using transgenic mice that overexpress the human calpastatin (hCAST) construct under control of a neuron-specific calcium-calmodulin dependent kinase II alpha or a ubiquitous prion protein promoter. Both transgenic lines exhibited enhanced calpastatin expression within the brain, extending into peripheral tissues under the prion protein promoter. hCAST overexpression significantly reduced protease activity confirmed by reductions in acute calpain-mediated substrate proteolysis in the cortex and hippocampus following controlled cortical impact brain injury. Aspects of posttraumatic motor and cognitive behavioral deficits were also lessened in hCAST transgenic mice compared to their wildtype littermates. However, volumetric analyses of neocortical contusion revealed no histological neuroprotection at either acute or long-term time points in either transgenic line. Partial hippocampal neuroprotection observed at a moderate injury severity in neuron-specific calpastatin overexpressing transgenic mice was lost after severe TBI. Greater levels of calpastatin under the prion protein promoter line failed to protect against hippocampal cell loss after severe brain injury. This study underscores the effectiveness of calpastatin overexpression in reducing calpain-mediated proteolysis and behavioral impairment after TBI, supporting the therapeutic potential for calpain inhibition. However, the reduction in proteolysis without accompanied neocortical neuroprotection suggests the involvement of other factors that are critical for neuronal survival after contusion brain injury. Augmenting calpastatin levels may be an effective method for calpain inhibition and may have efficacy in reducing behavioral morbidity after TBI and neurodegenerative disorders.

Spinal cord injury (SCI) is a debilitating condition accompanied by motor and sensory deficits and a reduced quality of life. Current treatment options are limited and are associated with variable efficacy and a risk of adverse effects. The pathophysiology of SCI is initiated by a primary mechanical insult to the spinal cord, followed by a complex series of deleterious events known as secondary injury. Secondary injury processes include free radical formation, glutamate excitotoxicity, inflammation and cell death. Apoptotic cell death in particular plays a key role in the secondary injury processes and exacerbates tissue degradation and loss of function. The role of Fas-mediated apoptosis in SCI pathophysiology is poorly defined in the literature to date. Correlative evidence suggests that this form of cell death is delayed and occurs in white matter adjacent to sites of primary damage. The cellular and temporal mechanisms of Fas-mediated apoptosis following experimental SCI were evaluated using a clinically relevant clip compression SCI model in the rat. Furthermore, therapeutic manipulation of Fas activation using a soluble form of the Fas receptor (sFasR) was carried out to establish the efficacy and clinical relevance of targeting this aspect of secondary injury. This work shows that Fas-mediated apoptosis is an important contributor to secondary SCI pathology. Oligodendrocytes are targeted by this form of cell death in a delayed fashion post-injury, providing an opportunity for therapeutic intervention. Intrathecal administration of sFasR following SCI reduced post-traumatic apoptosis, improved cell survival, enhanced tissue preservation and resulted in an improved motor recovery. Administration of sFasR was effectively delayed by up to 24 hours post-injury, however a shorter delay of 8 hours post-injury was most efficacious. A surprising result emerged from this work. Delayed intrathecal administration of IgG following SCI showed significant efficacy in both cellular and tissue level outcomes, as well as at the functional level. Fas-mediated apoptosis is an important aspect of secondary SCI pathophysiology and is an attractive therapeutic target. The beneficial outcomes of manipulating Fas activation using sFasR provide further evidence for this. Future work will refine this treatment strategy, bringing it into the SCI patient population.

Remote ischemic conditioning (RIC) is a noninvasive procedure where blood flow to a limb is repetitively reduced, sometimes called an “exercise memetic”. RIC delivered before (pre-RIC) or after (post-RIC) stroke is reportedly neuroprotective in preclinical stroke models. A review of the preclinical RIC literature revealed that studies almost exclusively use male subjects and a single stroke model (MCAO) that produces a large injury (~34% of hemisphere). To improve clinical translation, efficacy should be demonstrated in multiple stroke models and both sexes. Furthermore, the restorative potential of RIC (delivered past the neuroprotection window) to improve stroke recovery remains to be investigated. In male and female Sprague-Dawley rats (n=129) a standardized session (5min inflation, 5min deflation, 4 repetitions) of RIC was delivered using a pressurized cuff on the hindlimb. RIC was either delivered once 18h before, once 4hr acutely after or daily for 28 days beginning day 5 after endothelin-1 (ET-1) stroke. Infarct volumes were assessed 24hrs after stroke using MRI. To determine if RIC efficacy varied across stroke size, a hierarchical cluster analysis was used to divide rats into subgroups based on stroke size (small/large). RIC was effective in ET-1 which produced smaller strokes (“small”:5.2%, “large”:18.0% of hemisphere) than MCAO (~34%). This is more comparable to injury sizes seen clinically (4.5-14.0%). “Small” (42±4mm3) strokes were reduced by 39% (p=0.010, d=0.29) and “large” (146±8mm3) strokes were reduced by and 35% (p<.00001, d=1.41). Pre-RIC reduced infarct volume by 41% (p=<0.0001, d=0.92) versus 29% (p=0.009, d=0.43) in post-RIC. Interestingly, RIC is more effective in males, with double the infarct volume reduction of 46% (p<0.0001, d=0.94) compared with 23% (p=0.013, d=0.42) in females. Although RIC did not show restorative potential to improve motor stroke recovery, RIC is neuroprotective now with stronger clinically relevant evidence. RIC is effective across stroke models, stroke sizes and sex. Application of RIpreC to prevent stroke following a transient ischemic attack or recurrent stroke (especially in males with “large" strokes) would have the greatest potential.

Introdução: Hidrocefalia é uma síndrome caracterizada pelo acúmulo de líquido cérebroespinal no interior das cavidades ventriculares. Considerando a sua fisiopatologia de caráter multifatorial um dos fatores envolvidos é o estresse oxidativo desencadeado pela peroxidação lipídica e formação de radicais livres. O Edaravone é um novo fármaco antioxidante com efeitos neuroprotetores, que ainda não foi testado em pacientes com hidrocefalia. Objetivo: Avaliar a resposta neuroprotetora do Edaravone na hidrocefalia experimental em ratos jovens. Metodologia: A hidrocefalia foi induzida em ratos filhotes, injetando uma porção de caulim na cisterna magna. Os animais foram divididos em três grupos: controle (C) (n=10); hidrocefalia não tratada (HNT) (n=20); hidrocefalia tratado com 20mg/kg Edaravone (HTE) (n=20). O grupo tratado com a droga recebeu todos os dias, a partir do primeiro dia após a indução, uma injeção intraperitoneal com o Edaravone. Os animais foram pesados diariamente, avaliados por testes comportamentais e exame de ressonância magnética, análise histopatológica, imunoistoquímica e bioquímica. Todos os animais foram sacrificados, 14 dias após a indução de hidrocefalia. Resultados: Do terceiro ao oitavo dia após a indução de hidrocefalia, os animais ganharam menos peso do que os controles. No entanto, a partir do nono dia pós-indução, o ganho de peso foi similar nos três grupos experimentais. No teste de campo aberto e no labirinto aquático, o desempenho dos animais do grupo HTE foi melhor, quando comparado com os animais do grupo HNT. Na imunoistoquímica para GFAP, os animais do grupo HNT demonstravam astrócitos intensamente marcados com extensões grossas, enquanto que os animais do grupo de HTE tinham astrócitos mais delicados e com extensões finas. Na análise por caspase-3 os animais tratados com Edaravone mostraram um número menor de células em processos de apoptose. Conclusões: O uso do Edaravone evidenciou uma tendência a diminuir células em processo de apoptose, melhorou a resposta comportamental, e atividade dos astrócitos ligeiramente reduzida evidenciado por GFAP imunomarcação no corpo caloso de ratos jovens com hidrocefalia / Background: Hydrocephalus is a syndrome resulting from the current unbalance between the formation and absorption of cerebrospinal fluid (CSF), and consequent accumulation within the cerebral ventricles. Clinically, hydrocephalic children can present several neurological disorders, not always reversed with treatment, even after the development of more and more sophisticated shunt systems (1). Although lesions of hydrocephalus be multifactorial, it is known that oxidative stress is one of the mechanisms involved. The Edaravone is a new antioxidant drug with neuroprotective effects but has not been tested in hydrocephalus (2). Objectives: To evaluate the neuroprotective response of Edaravone on experimental hydrocephalus in young rats. Methodology: Hydrocephalus was induced in pup rats by injecting kaolin into the cisterna magna. The animals were divided into three groups with 10 rats each one: control (C); untreated hydrocephalus (HNT); hydrocephalus treated with 20mg/kg Edaravone (HTE). The treated group receive the drug every day from the first day after induction. The animals were weighed daily, assessed by behavioral tests and magnetic resonance examination. All animals were sacrificed 14 days after hydrocephalus induction and the brains processed for histological, immunohistochemical and biochemical analysis. In the analysis of caspase-3 treated animals showed Edaravone a smaller number of cells in the process of apoptosis. Results: From the third to the eighth day after the hydrocephalus induction, the animals gained less weight than controls. However, from the ninth day of induction, weight gain was similar in the 3 experimental groups. In the open field test the performance of hydrocephalic rats receiving Edaravone was better than those who did not receive the drug. In immunohistochemistry for GFAP in the corpus callosum, the control rats did not exhibit reactive astrocytes. On the other hand, the animals of HNT group showed intensely labeled astrocytes with thick extensions, while the animals in the HTE group the astrocytes were more delicate and with thin extensions. Conclusion: The use of Edaravone showed a tendency to decrease in cell apoptosis improved the behavioral response and slightly reduced astrocyte activity evidenced by GFAP immunostaining in the corpus callosum of young rats with hydrocephalus

A hidrocefalia é uma condição neurológica complexa, em que ocorre o desequilíbrio na dinâmica do líquido cefalorraquidiano (LCR) provocando um distúrbio na produção, circulação e reabsorção do mesmo, o que pode levar a uma redução e/ou bloqueio do fluxo sanguíneo. Apesar do tratamento com derivação liquórica ser eficiente na redução da ventriculomegalia, muitos danos neurológicos não são revertidos com a cirurgia. Estudos demonstram que o estresse oxidativo está envolvido na gênese das lesões da hidrocefalia. O objetivo deste trabalho foi avaliar a resposta neuroprotetora do Resveratrol, reconhecido como um potente antioxidante, na hidrocefalia experimental induzida em ratos Wistar jovens. Foram utilizados ratos machos, com sete dias de vida, que receberam uma injeção de caulim a 15% na cisterna magna para indução da hidrocefalia. Esses animais foram divididos em grupo hidrocefálico sem tratamento (n=20), grupo hidrocefálico tratado com Resveratrol através de aplicação de injeção intraperitoneal (20mg/kg/dia) (n=20) e um grupo de animais que não receberam a injeção de caulim para ser usado como controle (n=10). Foram realizadas avaliações comportamentais e estudos de ressonância magnética. Duas semanas após, os animais foram eutanasiados para coleta dos encéfalos, e realizados testes histológicos, imunoistoquímicos e bioquímicos. Os resultados obtidos neste trabalho mostraram que os animais hidrocefálicos, que receberam diariamente injeção de Resveratrol, apresentaram efeito benéfico nos testes comportamentais mostrando mais agilidade e melhor exploração do ambiente, melhor desenvolvimento sensoriomotor, aprendizagem e capacidade de memorização, apresentaram também discreta diminuição da atividade astrocitária evidenciada pela imunomarcação do GFAP no corpo caloso e exibiram aumento significativo na quantidade de antioxidantes totais no plasma. Conclui-se que o uso do Resveratrol diminuiu a atividade astrocitária, aumentou a quantidade de antioxidantes e melhorou a memória e o desenvolvimento motor dos ratos / Hydrocephalus is a neurological condition complex, wherein the imbalance occurs in the dynamics of cerebrospinal fluid (CSF) causing a disturbance in the production, circulation and absorption thereof, which can lead to a reduction and / or blockage of blood flow. Despite treatment with CSF shunt be effective in reducing ventriculomegaly, many neurological damage is not reversed with surgery. Studies have shown that oxidative stress is involved in the genesis of hydrocephalus injuries. The objective of this study was to evaluate the neuroprotective response Resveratrol, recognized as a potent antioxidant in experimentally induced hydrocephalus in young Wistar rats. male rats were used with seven days of life, which received a 15% kaolin injection into the cisterna magna induction of hydrocephalus. These animals were divided into hidrocefálico untreated group (n = 20), hidrocefálico group treated with resveratrol by intraperitoneal injection application (20 mg / kg / day) (n = 20) and a group of animals that received the kaolin injection to be used as control (n = 10). behavioral assessments and magnetic resonance studies were performed. Two weeks later, the animals were euthanized to collect the brains and performed histological, immunohistochemical and biochemical tests. The results of this study showed that hidrocefálicos animals that received daily injection of Resveratrol showed beneficial effect on behavioral tests showing more agility and better exploitation of the environment, better sensorimotor development, learning and memory capacity, also showed a slight decrease of astrocyte activity evidenced by immunostaining of GFAP in the corpus callosum and exhibited a significant increase in the total amount of antioxidants in plasma. We conclude that the use of Resveratrol decreased the astrocyte activity, increased the amount of antioxidants and improved memory and motor development of mice

A hidrocefalia é uma condição neurológica complexa, em que ocorre o desequilíbrio na dinâmica do líquido cefalorraquidiano (LCR) provocando um distúrbio na produção, circulação e reabsorção do mesmo, o que pode levar a uma redução e/ou bloqueio do fluxo sanguíneo. Apesar do tratamento com derivação liquórica ser eficiente na redução da ventriculomegalia, muitos danos neurológicos não são revertidos com a cirurgia. Estudos demonstram que o estresse oxidativo está envolvido na gênese das lesões da hidrocefalia. O objetivo deste trabalho foi avaliar a resposta neuroprotetora do Resveratrol, reconhecido como um potente antioxidante, na hidrocefalia experimental induzida em ratos Wistar jovens. Foram utilizados ratos machos, com sete dias de vida, que receberam uma injeção de caulim a 15% na cisterna magna para indução da hidrocefalia. Esses animais foram divididos em grupo hidrocefálico sem tratamento (n=20), grupo hidrocefálico tratado com Resveratrol através de aplicação de injeção intraperitoneal (20mg/kg/dia) (n=20) e um grupo de animais que não receberam a injeção de caulim para ser usado como controle (n=10). Foram realizadas avaliações comportamentais e estudos de ressonância magnética. Duas semanas após, os animais foram eutanasiados para coleta dos encéfalos, e realizados testes histológicos, imunoistoquímicos e bioquímicos. Os resultados obtidos neste trabalho mostraram que os animais hidrocefálicos, que receberam diariamente injeção de Resveratrol, apresentaram efeito benéfico nos testes comportamentais mostrando mais agilidade e melhor exploração do ambiente, melhor desenvolvimento sensoriomotor, aprendizagem e capacidade de memorização, apresentaram também discreta diminuição da atividade astrocitária evidenciada pela imunomarcação do GFAP no corpo caloso e exibiram aumento significativo na quantidade de antioxidantes totais no plasma. Conclui-se que o uso do Resveratrol diminuiu a atividade astrocitária, aumentou a quantidade de antioxidantes e melhorou a memória e o desenvolvimento motor dos ratos / Hydrocephalus is a neurological condition complex, wherein the imbalance occurs in the dynamics of cerebrospinal fluid (CSF) causing a disturbance in the production, circulation and absorption thereof, which can lead to a reduction and / or blockage of blood flow. Despite treatment with CSF shunt be effective in reducing ventriculomegaly, many neurological damage is not reversed with surgery. Studies have shown that oxidative stress is involved in the genesis of hydrocephalus injuries. The objective of this study was to evaluate the neuroprotective response Resveratrol, recognized as a potent antioxidant in experimentally induced hydrocephalus in young Wistar rats. male rats were used with seven days of life, which received a 15% kaolin injection into the cisterna magna induction of hydrocephalus. These animals were divided into hidrocefálico untreated group (n = 20), hidrocefálico group treated with resveratrol by intraperitoneal injection application (20 mg / kg / day) (n = 20) and a group of animals that received the kaolin injection to be used as control (n = 10). behavioral assessments and magnetic resonance studies were performed. Two weeks later, the animals were euthanized to collect the brains and performed histological, immunohistochemical and biochemical tests. The results of this study showed that hidrocefálicos animals that received daily injection of Resveratrol showed beneficial effect on behavioral tests showing more agility and better exploitation of the environment, better sensorimotor development, learning and memory capacity, also showed a slight decrease of astrocyte activity evidenced by immunostaining of GFAP in the corpus callosum and exhibited a significant increase in the total amount of antioxidants in plasma. We conclude that the use of Resveratrol decreased the astrocyte activity, increased the amount of antioxidants and improved memory and motor development of mice

Introdução: Hidrocefalia é uma síndrome caracterizada pelo acúmulo de líquido cérebroespinal no interior das cavidades ventriculares. Considerando a sua fisiopatologia de caráter multifatorial um dos fatores envolvidos é o estresse oxidativo desencadeado pela peroxidação lipídica e formação de radicais livres. O Edaravone é um novo fármaco antioxidante com efeitos neuroprotetores, que ainda não foi testado em pacientes com hidrocefalia. Objetivo: Avaliar a resposta neuroprotetora do Edaravone na hidrocefalia experimental em ratos jovens. Metodologia: A hidrocefalia foi induzida em ratos filhotes, injetando uma porção de caulim na cisterna magna. Os animais foram divididos em três grupos: controle (C) (n=10); hidrocefalia não tratada (HNT) (n=20); hidrocefalia tratado com 20mg/kg Edaravone (HTE) (n=20). O grupo tratado com a droga recebeu todos os dias, a partir do primeiro dia após a indução, uma injeção intraperitoneal com o Edaravone. Os animais foram pesados diariamente, avaliados por testes comportamentais e exame de ressonância magnética, análise histopatológica, imunoistoquímica e bioquímica. Todos os animais foram sacrificados, 14 dias após a indução de hidrocefalia. Resultados: Do terceiro ao oitavo dia após a indução de hidrocefalia, os animais ganharam menos peso do que os controles. No entanto, a partir do nono dia pós-indução, o ganho de peso foi similar nos três grupos experimentais. No teste de campo aberto e no labirinto aquático, o desempenho dos animais do grupo HTE foi melhor, quando comparado com os animais do grupo HNT. Na imunoistoquímica para GFAP, os animais do grupo HNT demonstravam astrócitos intensamente marcados com extensões grossas, enquanto que os animais do grupo de HTE tinham astrócitos mais delicados e com extensões finas. Na análise por caspase-3 os animais tratados com Edaravone mostraram um número menor de células em processos de apoptose. Conclusões: O uso do Edaravone evidenciou uma tendência a diminuir células em processo de apoptose, melhorou a resposta comportamental, e atividade dos astrócitos ligeiramente reduzida evidenciado por GFAP imunomarcação no corpo caloso de ratos jovens com hidrocefalia / Background: Hydrocephalus is a syndrome resulting from the current unbalance between the formation and absorption of cerebrospinal fluid (CSF), and consequent accumulation within the cerebral ventricles. Clinically, hydrocephalic children can present several neurological disorders, not always reversed with treatment, even after the development of more and more sophisticated shunt systems (1). Although lesions of hydrocephalus be multifactorial, it is known that oxidative stress is one of the mechanisms involved. The Edaravone is a new antioxidant drug with neuroprotective effects but has not been tested in hydrocephalus (2). Objectives: To evaluate the neuroprotective response of Edaravone on experimental hydrocephalus in young rats. Methodology: Hydrocephalus was induced in pup rats by injecting kaolin into the cisterna magna. The animals were divided into three groups with 10 rats each one: control (C); untreated hydrocephalus (HNT); hydrocephalus treated with 20mg/kg Edaravone (HTE). The treated group receive the drug every day from the first day after induction. The animals were weighed daily, assessed by behavioral tests and magnetic resonance examination. All animals were sacrificed 14 days after hydrocephalus induction and the brains processed for histological, immunohistochemical and biochemical analysis. In the analysis of caspase-3 treated animals showed Edaravone a smaller number of cells in the process of apoptosis. Results: From the third to the eighth day after the hydrocephalus induction, the animals gained less weight than controls. However, from the ninth day of induction, weight gain was similar in the 3 experimental groups. In the open field test the performance of hydrocephalic rats receiving Edaravone was better than those who did not receive the drug. In immunohistochemistry for GFAP in the corpus callosum, the control rats did not exhibit reactive astrocytes. On the other hand, the animals of HNT group showed intensely labeled astrocytes with thick extensions, while the animals in the HTE group the astrocytes were more delicate and with thin extensions. Conclusion: The use of Edaravone showed a tendency to decrease in cell apoptosis improved the behavioral response and slightly reduced astrocyte activity evidenced by GFAP immunostaining in the corpus callosum of young rats with hydrocephalus

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Background: Oxidative stress induced by reactive oxygen species has been strongly associated with many neurodegenerative diseases (NDDs) and many medicinal plant-derived products have been reported to exert potent antioxidant properties. Sutherlandia frutescens (SF) and Carpobrotus edulis (CE) are two indigenous South African plants with known anti-inflammatory, anti-bacterial, antioxidant and anti-cancer properties. However, the neuroprotective effects of SF and CE have not been extensively studied. Aims: This study was done to investigate the neuroprotective potentials of S. frutescens and C. edulis aqueous extracts on hydrogen peroxide (H2O2)-induced toxicity in an SH-SY5Y neuroblastoma cellular model of oxidative stress injury. Methods: The maximum non-toxic dose (MNTD) of SF and CE against SH-SY5Y cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Thereafter, the cells were exposed to 250 μM H2O2 for 3 hours before treatment with the determined MNTDs of SF and CE extracts respectively and the effects of the treatments on caspase-9 protease activity, intracellular ROS levels, mitochondrial membrane permeability (MMP), nitric oxide (NO) activity, intracellular calcium activity and endogenous antioxidant activity in SH-SY5Y cells was evalaluated using caspase activity kits, DCFH-DA assay, rhodamine 123 fluorescent dye, Griess reagent, Fluo-4 direct calcium reagent, Hoechst staining dye, Superoxide dismutase (SOD) colorimetric and Catalase (CAT) assays, respectively.