Navegando por Assunto "Acidente vascular cerebral"

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Acesso aberto (Open Access)
Acidente vascular encefálico isquêmico na exposição crônica ao etanol: estudo pré-clínico da comorbidade e da resposta a minociclina
(Universidade Federal do Pará, 2015-02-27) FONTES JÚNIOR, Enéas de Andrade; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Stroke is the second largest cause of death in the world and the leading in Brazil, with 87% of strokes due to ischemic processes. Chronic ethanol consumption, usually beginning in adolescence, is recognized as an independent risk factor for increased morbidity and mortality by stroke. Although cases combining the two diseases are relatively common, there is no data in animals or clinical models demonstrating the quality or mechanisms of interaction between the two morbidities, nor its impact on therapeutic intervention. Considering the recent studies proposing minocycline as a new therapeutic tool for the treatment of stroke, this study aimed to investigate the interaction between the Chronic Alcoholic Intoxication (CAI) started in adolescence and the stroke in motor cortex of adult rats, and the effects of treatment with minocycline on this interaction, using behavioral, cellular and molecular parameters. Female Wistar rats (35 days-old) were chronically exposed to ethanol (6.5 g/kg/day, 22.5% w/v) or water for 55 days. One day after the end of the CAI focal ischemia was induced in motor cortex with the endothelin-1 (ET-1), followed by seven-day treatment with minocycline or saline. After this period, the animals were assayed with open field and rota rod tests. Immediately, animals were sacrificed and cortex was dissected for evaluation of nitrite and lipid peroxidation levels. In all groups, some animals were perfused and the motor cortex subjected to histological analysis to assess the damage, and immunohistochemical labeling to neuronal death (anti-NeuN), microglial/macrophage (anti-ED1) and astrocytes (anti-GFAP) activation. The ethanol intoxication from puberty to adulthood potentiated the damage caused by stroke, causing major losses in capacity to start and running movements as well as the strength and motor coordination compared to ischemic animals pretreated with water. These manifestations were accompanied by increased neuronal loss, reduced ED-1+ and GFAP+ cells and higher levels of nitrite and lipid peroxidation. Treatment with minocycline was effective in preventing/reverse motor deficits and tissue damage induced by focal ischemia, also inhibiting the increase in oxidative stress markers. The CAI either alone with succeeded by focal ischemia, harmed the outcome of treatment with minocycline. Our results indicate that heavy alcohol intoxication during adolescence exacerbates the motor deficit and tissue damage in animals subjected to focal ischemia. This process appears to be associated with microglia/astroglial activation, but mainly with oxidative stress. It also shows that the previous history of CAI started adolescence interferes significantly in the treatment of cerebral ischemia with minocycline.
Acesso aberto (Open Access)
Alterações morfo-funcionais em córtex isquêmico de animais tratados com transplante autólogo de células mononucleares da medula óssea
(Universidade Federal do Pará, 2015-10-08) BARBOSA JUNIOR, Mário Santos; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644
Statistical data show stroke as the second leading cause of death and leading cause of disability among all other diseases in the world. The ischemic stroke (ischemic stroke) accounts for about 87% of incidence of strokes. In ischemic stroke, inflammation acts in restraint of infarction caused by ischemic stroke, and on the other hand the intensity of the inflammatory response in neurodegeneration and consequently influence the functional loss. The autologous cell therapy, mononuclear bone marrow cells, promotes modulation in neuroinflammation, being timely during an ischemic event for reduction of tissue loss and functional. In the present study, we used an experimental model of focal ischemic stroke to assess morphological and functional effects of autologous implant mononucleres bone marrow cells (CMMOs) on the morphological and functional changes related to ischemic stroke. We demonstrate in this study that the autologous BM-MNC in acute or acute and subacute periods of ischemic event, promoted neuroprotection and inflammatory modulation able to rebound in preservation and functional recovery in specific activities. We also show that the treatment enhanced in subacute period, the ischemic event, was able to promote increase in morphological and functional improvements promoted by autologous transplantation in acute period.
Acesso aberto (Open Access)
Análise comparativa dos padrões neurodegenerativos da substância cinzenta em diferentes áreas corticais de ratos adultos submetidos à lesão isquêmica focal
(Universidade Federal do Pará, 2012-09-27) SANTOS, Enio Maurício Nery dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke can occur in any region of the central nervous system (CNS). The cerebral cortex is one of the most often affected areaby this acute neural disorder, but there are no studies that have compared the damaging pattern in different cortical regions after acomparable focal ischemia. The aim of this investigation was to evaluate the degenerative pattern of different cortical areas after focal ischemic injury. Focal ischemia was induced by stereotaxic microinjections of endothelin-1 (ET-1) into the somatosensory, motor and association cortices of adult rats (N = 45). The control animals were injected with the same volume of sterile saline (N = 27). The animals were perfused 1, 3 and 7 days after the ischemic event. The brain was removed, postfixed, cryoprotected, and sectioned in a cryostat. The general histopathology was evaluated in 50μm sections stained with cresyl violet. 20μm sections were submitted to immunohistochemistry for astrocytes (anti-GFAP), activated microglia / macrophages (anti-ED1) and overall microglial population (anti-Iba1). The damaging patterns werequalitatively evaluated under optical microscopy and quantitatively by counting the number of cells in the ipsilateral and contralateral sides to injury.Descriptive statistics and comparisons within and between groups were performed using analysis of variance with Tukey post-hoc test. Conspicuous ischemic tissue loss, microglial activation and astrocytosis were observed mainly 3 and 7 days after ischemia, which was not observed in control animals. The tissue loss and activation of glial cells were more intense in the somatosensory cortex, followed by the motor cortex. The association cortex displayed less damage compared to other cortical areas, which was confirmed by quantitative analysis. The results suggest that an ischemic lesion of the same intensity induces a differential pattern of tissue loss and neuroinflammation, depending on the cortical area, and that the primary sensory and motor areas are more susceptible to ischemia than association areas.
Acesso aberto (Open Access)
Ativação microglial, lesão da substância branca e expressão de Nogo-A em ratos submetidos à isquemia estriatal
(Universidade Federal do Pará, 2012-05-10) LIMA, Rafael Rodrigues; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
The objective of this investigation was to evaluate the degenerative pattern of several white matter tracts after striatal ischemic injury, correlating degenerative process standards with the microglial activation and expression of Nogo-A. For this purpose, focal ischemia was induced with stereotactic injection of endothelin in striatum of adult rats, and only in the control animals injected with sterile saline. The animals were perfused 3, 7, 14 and 30 days after ischemia. The brain removed, postfixed, cryoprotected, cut into cryostat sections obtained and submitted to immunohistochemical investigation with the following antibodies: anti-GFAP (1:2000, Dako), anti-Tau-1 (1:500, Chemicon), Anti-MBP (1:100, Chemicon International), Anti-Nogo-A (1:100, Invitrogen), Anti-Iba1 (1:1000, WAKO), ED1 (1:500, Serotec) and Anti-MHC II (Abcam 1:100), besides the viewing of the damage pattern with cresyl violet. Slides are marked by different methods were evaluated qualitatively and quantitatively also some (Anti-Nogo A, anti-ED-1, anti-MHC-II and anti-tau-1), counts were carried out in the striatum and in the corpus callosum. The data were tabulated, statistically analyzed by Tukey test (p <0.05) and micrographs taken of the findings more representative. The slides were stained with cresyl violet revealed an increase in cell density by the infiltration of inflammatory cells to the ischemic area, with a significant increase on day 7. The blades immunostained for GFAP was found progressive increase of the population of astrocytes and an increase in cell volume 7 and 14 days. Oligodendrocyte pathology marked with Tau-1 had peak marking the 3rd day in the striatum and the 7th day in the corpus callosum, and loss of myelin compaction identified by MBP was better at 14, in the different treatment. The microglial activation identified by different immunoblots showed a peak on day 7, both in striatum and in the corpus callosum, but in the corpus callosum with a much smaller number compared to the striatum. The morphology of microglial underwent changes, which found the branched phenotype in control animals, as well as in early and late times after ischemia and amoeboid default / phagocytic day 7, coinciding with the largest number of activated cells. The count of Nogo-A + cells peaked at 3 days observed in the striatum, and there were no differences in the corpus callosum expression Nogo-A 3 to 14 days, only a decrease compared to 30 days. Thus, microinjections of ET-1 induced conspicuous striatal tissue loss, concomitant with progressive microglial activation, astrocytosis, loss of immunoreactivity for myelin basic protein and oligodendrocytes damage in various survival times after focal ischemia. These events affect a few SB tracts, as the corpus callosum. The establishment of the temporal evolution of these events is the neuropathological basis for future studies, in which they should handle the inflammatory response in order to minimize these tissue changes.
Acesso aberto (Open Access)
Atividade antiinflamatória e neuroprotetora da Edaravona no córtex sensóriomotor primário de ratos adultos submetidos à isquemia focal experimental
(Universidade Federal do Pará, 2014-02-12) ARAÚJO, Sanderson Corrêa; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke is a neural disorder originated from blood flow decreasing or interruption, making inadequate energy supply in the region, thus promoting tissue damage. The stroke can be divided in hemorragic or ischemic. The ischemic stroke is more prevalent and can occur through thrombosis or embolism. The ischemic pathology has multiple interrelated events like excitotoxicity, peri-infarct depolarization, oxidative and nitrosative stress, inflammation and apoptosis. An element of fundamental importance in ischemic pathology is the microglial cell, whose activity is closely linked to the progression of environment harm. A therapeutic alternative in the treatment of stroke is a pyrazolone called Edaravone. This study evaluated the neuroprotective effect of Edaravone dose of 3mg/kg in primary sensorymotor cortex after focal ischemic lesion. Edaravone treated animals (N = 10) and animals treated with saline solution (N = 10) in the survival time of 1 and 7 days after the ischemic event was evaluated. Treatment whith edaravone showed by histopathological analysis with cresyl violet a reduction of 49% and 66% in infarct size in animals in survival time 1 and 7 days respectively. Immunohistochemistry studies for microglia/macrophages assets (ED1+) demonstrated a reduction in the presence of ED1+ cells in 35% and 41% survival times for 1 and 7 days, respectively. Neutrophils (MBS-1+) were reduced to 64% only in animals with survival times a day. Harmful patterns were assessed qualitatively and quantitatively. Data was tested by ANOVA with Tukey post hoc test. Differences were considered significant at p < 0,05.
Acesso aberto (Open Access)
Efeito combinado do exercício físico e da degradação da matriz extracelular na plasticidade do córtex cerebral após isquemia
(Universidade Federal do Pará, 2014-04-14) CASTRO, Ketlin Jaquelline Santana de; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170
Cerebrovascular diseases are major cause of neurological disability and death in Brazil, and more than 80% of them are caused by ischemic stroke. The survivors subsist with a variety of sensory, cognitive and motor deficits. Therefore, it becomes necessary to develop therapeutic strategies to promote functional recovery in this patients. After ischemia, there is an increase in the inhibitory molecules expression as proteoglycans of chondroitin sulfate (CSPGs) presents in the extracellular matrix of the nervous tissue. The removal of these molecules, as well as physical exercise, have been used as strategy to induce another window of brain plasticity and improve functional recovery. In this work, we running experimental ischemic injury on sensorimotor areas forepaw representation (S1/M1) and tested associations between removal of CSPGs and physical exercise in n=16 Wistar rats (Rattus norvegicus). To delivery drugs to the forepaw representation in the cerebral cortex, we used a biomembrane previously ChABC-saturated or BSA-saturated and all animals had 21 days of survival divided in: Control group or BSA; Exercise group; ChABC group; and ChABC + Exercise group. The lesion area was no different across groups (control: 0,48±0,12; exercise: 0,46±0,05; ChABC: 0,50±0,18; ChABC+exercise: 0,50±0,18; ANOVA and Tukey post-test). Animals that were subjected to CSPGs enzymatic removal showed immunostaining for anti-chondroitin-4-sulphate (C4S) antibody in lesion area at the end of survival, with no evidence of CSPGs degradation in Control and Exercise groups. We evaluated the functional recovery of affected paw running vertical exploration test and ladder rung walking test. The vertical exploration test showed ischemic injury did not cause extensive functional loss, not changing exploratory behavior, or the use frequency of the affected forepaw after injury (Control group: baseline (0,03±0,10), 3d (0,29±0,17), 7d (0,30±0,10), 14d (0,29±0,16) e 21d (0,27±0,13) days after injury; Exercise group: baseline (0,30±0,12), 3d (0,32±0,24), 7d (0,19±0,37), 14d (0,31±0,10) e 21d (0,32±0,09) days after injury; ChABC group: baseline (0,34±0,07), 3d (0,20±0,11), 7d (0,23±0,07), 14d (0,33±0,14) e 21d (0,39±0,16) after injury; ChABC + Exercício group: baseline (0,34±0,04), 3d (0,20±0,09), 7d (0,26±0,04), 14d (0,18±0,08) e 21d (0,27±0,04) after injury (ANOVA and Tukey post-test). The group that only had removing CSPGs presented a better performance on Ladder rung walking test but at the end of the 21-day survival, the control groups and ChABC + Exercise reached a spontaneous recovery (equivalent to pre-injury test) reaching the ChABC group. The group treated with Exercise did not achieve the spontaneous recovery showing a motor performance significantly lower than other groups at all times of reevaluation (baseline: 8,40±0,28; 3d: 4,30±0,48; 7d: 4,75±0,50; 14d 5,35±0,41; 21d: 5,05±0,67; ANOVA and Tukey post-test). We conclude that the removal of CSPGs early improves motor performance in the affected forepaw after stroke on sensoriomotor cortex but associate with specific physical exercise doesn’t improve functional recovery.
Acesso aberto (Open Access)
Efeitos anti-inflamatórios e neuroprotetores do extrato de gergelim preto (Sesamum indicum L.) em um modelo experimental de isquemia estrial
(Universidade Federal do Pará, 2024-03) SANTOS, Ijair Rogério Costa dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Acidente Vascular Encefálico (AVE) é uma neuropatologia caracterizada como o surgimento súbito global ou focal de déficits da função neurológica de duração superior a 24 horas ou que leve a morte, cuja única causa reside na origem vascular. Estudos sobre a incidência, comprometimento físico e mortalidade enquadram o AVE como a segunda causa de morte no mundo e a principal complicação orgânica que leva às disfunções físico-neurológicas, frequentemente, graves e permanentes. A indução do AVE em animais de experimentação e o entendimento de sua fisiopatologia, bem como a busca de tratamentos que minimizem os danos neurológicos e estimulem a recuperação morfofuncional do indivíduo afetado são temas de grande relevância científica e clínica. Neste estudo, investigamos os possíveis efeitos neuroprotetores e/ou anti-inflamatórios do extrato supercrítico de gergelim preto (Sesamun indicum L.) após lesão isquêmica focal por microinjeções de 80 pmol de endotelina-1 no estriado de ratos adultos, usando as coordenadasestereotáxicas: 1,2 mm, anterior-posterior; 2,5 mm, médio-lateral; 4,0 mm, dorsoventral. Após a indução do AVE, os grupos controles foram tratados com tween a 5% e os tratados receberam 150 mg/kg de gergelim, ambos, por via intraperitoneal, em duas doses diárias de 75 mg/kg. A neuropatologia foi obtida em secções encefálicas com 50 e 20 μm de espessuras e coradas com violeta de cresila, para identificar a área de lesão, e/ou imunomarcadas por anticorpos específicos à identificação de neurônios (anti-NeuN), astrócitos (anti-GFAP) e micróglia (anti-ED1). Secções de 5 μm de espessura de rim e fígado corados por métodos histológicos e histoquímicos não mostraram alterações morfológicas nas células que compõem esses órgãos essenciais, sugerindo baixa toxicidade do extrato. Todas as secções coradas e/ou imunomarcadas foram visualizadas em microscópio óptico e seuscampos mais ilustrativos, em todos os tempos de sobrevida e grupos experimentais,foram capturados digitalmente e editados em computador. A quantificação das célulasNeuN+(neurônios), micróglia/macrófagos (ED1+) e astrócitos (GFAP+) na área de lesão, três secções por lâmina, todo campo ao redor de lesão por secção, com auxílio de uma gradícula de área 0,0625 mm2 na ocular possibilitou o teste t-Student à análise estatística entre os grupos e o uso do programa Microsoft Excel à plotagem dos gráficos. Por fim, uma caracterização da citotoxicidade in vitro, bem como a verificação do índice de acidez do extrato revelou baixa acidez e mínima agressividade em células sanguíneas, que ratifica o uso do extrato supercrítico em estudos que visem otratamento de doenças agudas e crônicas no SNC.
Acesso aberto (Open Access)
Efeitos da Curcuma longa em modelo murino de acidente vascular cerebral
(Universidade Federal do Pará, 2024-09) SANTOS, Vitória Corrêa; RÊGO, Dielly Catrina Favacho Lopes; http://lattes.cnpq.br/1810961422826950; https://orcid.org/0000-0002-6226-4269
Stroke is the third leading cause of death and the main cause of functional impairment in adults. It can be hemorrhagic in nature, when a blood vessel in the brain ruptures, or ischemic, when there is obstruction of cerebral arterial blood flow. Ischemic stroke accounts for 87% of cases and is characterized by excitotoxicity, oxidative stress, neuroinflammation and cell death. Currently, treatment for ischemic stroke is limited to tissue plasminogen activator (tPA) therapy or mechanical thrombectomy, which makes the search for new pharmacological approaches crucial. In this scenario, Curcuma longa Linn (C. longa), known as turmeric, is a plant popularly used in cooking and traditional medicine and its main active compound is curcumin, responsible for giving C. longa anti-inflammatory, antioxidant, antimicrobial, antitumor, anticancer effects, among others. In the literature, C. longa has demonstrated promising activity against lesions caused by cerebral ischemia; however, the prolonged effects of the compound remain unknown. In this sense, this study evaluated the possible neuroprotective effects of C. longa in a murine model of transient focal cerebral ischemia. For that, 20 adult male Wistar rats (8 weeks old, weighing 300 ± 20 g; CEUA-UFPA no. 6868300622 [ID 001229]) underwent middle cerebral artery occlusion (MCAO) surgery for 30 minutes and treated with C. longa (MOTORE®) at a dose of 80 mg/kg every 12 hours for 14 days. The animals were divided into 4 groups (n = 4-5 animals per group): 1) Sham + V (animals with sham surgery that received vehicle [0.5 M NaOH + PBS]), 2) Sham + CL (animals with sham surgery that received C. longa), 3) MCAO + V (animals submitted to MCAO surgery that received vehicle) and 4) MCAO + CL (animals submitted to MCAO surgery that received C. longa). Metabolic parameters such as weight gain and water and food consumption were evaluated, as well as behavioral parameters through the neurological deficit score and the beam walking test, as well as histopathological parameters with the measurement of the infarct area and volume. In our results, no differences in body weight gain were found between the experimental groups. However, the sham + CL group consumed more water than the sham + V, MCAO + V and MCAO + CL groups, and the MCAO + CL group consumed less food on the 11th and 13th day after ischemia. Regarding behavioral deficits, both in the analysis of neurological deficit and in the beam walking test, the motor impairments evidenced by the MCAO + V and MCAO + CL groups were not attenuated by C.longa-treatment. Furthermore, treatment with C. longa did not attenuate the lesions caused by cerebral ischemia in our histological analyses. Thus, we conclude that treatment with Curcuma longa for 14 days did not exert a neuroprotective effect in the murine model of ischemic stroke, under our experimental conditions.
Acesso aberto (Open Access)
Imunoreatividade para os receptores de neurotrofinas P75NTR e TrkA na zona subventricular de ratos adultos após isquemia estriatal
(Universidade Federal do Pará, 2015-08-21) TAVARES, Patrycy Assis Noronha; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Neurotrophins are growth factors expressed by cells of the nervous system both during development and in adulthood. The Nerve Growth Factor (NGF, the English- Nerve Growth Factor), brain-derived neurotrophic factor (English- BDNF- of Brain-Derived Neurotrophic Factor), Neurotrophin-3 (NT-3), Neurotrophin-4/5 ( NT-4/5), have many functions related to aging and response of nervous tissue to the pathology such as vascular accident (CVA). In this pathology, the increase of the neurotrophin expression can interfere with the degree of neurogenesis in the sub-ventricular zone (SVZ) and redirect the rostral migratory flow of Adult Neural Stem Cells (CTNAs) to the ischemic region. The presence of neurotrophin receptors TrkA and p75NTR in the CTNAs of SVZ indicates that they may participate in the regulation of neurogenesis in this region. Here we describe the influence of an experimental ischemia by microinjection of a vasconstritor Endothelin-1 peptide, which is restricted to the striatum adjacent SVZ; on the pattern of immunoreactivity for TrkA and p75NTR receptors in different survival times. The histopathological pattern of ischemic striatum and the cytoarchitecture of the SVZ, followed by immunohistochemical analysis to the receptors were analyzed. Numerous p75NTR + cells were found in the ipsilateral SVZ and against the injection site, with had a reduction in immunoreactivity at first and third day after ischemia. Few TrkA + cells were found in SVZ of both groups, however, many TrkA + axonal terminals were saw in the ischemic ipsilateral SVZ. Soon after the ischemic process, there was thickening of the SVZ, the concomitant reduction in immunoreactivity for p75NTR and TrkA + arisings of axonal terminals.
Acesso aberto (Open Access)
Indução de plasticidade cerebral por remoção da matriz extracelular após lesão isquêmica no córtex sensório-motor de ratos
(Universidade Federal do Pará, 2012-12-14) SOARES, Soanne Chyara da Silva; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170
Stroke is the third major cause of mortality and disability in whole word and the major cause of death in Brazil. After ischemic injury, functional deficits are generally severe and permanent, because Central Nervous System has a limitated capacity of regeneration. This limitated regeneration is caused, among other factors, by chondroitin sulfate proteoglycans (CSPG) accumulation in injury site, what causes inhibition of plasticity in extracellular microenvironment. Chondroitinase-ABC enzyme (ChABC) has been studied to remove CSPG, showing good results in increasing plasticity. This research aimed to evaluate effects of CSPG removing in rats submitted to ischemic injury in sensory-motor cerebral cortex. To achieve the aim, there were used 20 Wistar rats, divided in 4 experimental groups (control and treated) of 7 and 14 days of surviving times. There was induced ischemic injury in sensorymotor cortex by microinjections of endothelin-1 (ET-1), a vasoconstrictor peptide. Treatment was done with an implantation of an ethyl-vinyl-acetate polymer saturated with ChABC (treated-group) or BSA (control group). In morphological analysis, we evaluated injury area. There was no significant difference between treated and control groups, as can be seen in means of each group: control 7 days (1653,8 ± 162,57mm²), treated 7 days (2067,3 ± 235,42mm²), control 14 days (1267,16 ± 280,6mm²), treated 14 days ( 1323,8 ± 297,05mm²). Number of astrocytes was evaluated too, but there was no significant difference between treated and control groups, as we can see in means: control 7 days (16,6±4,67 cells/field), treated 7 days (21,07±1,87 cells/field) control 14 days (17,46±0,80 cells/field), treated 14 days (18,51±2,60 cells/field). The expression of degraded chondroitin was evaluated in qualitative analysis, showing major expression in treated-groups, 7 and 14 days after injury. In behavioral analysis, we have done two functional tests. In cylinder test, treated animals had less asymmetry in 7 days after injury, with significant difference in relation to control group. In horizontal ladder test, treated animals had less difference between surviving groups than control animals. In 7 days after injury, treated animals had the same performance of preoperated baseline. Behavioral performances showed that ChABC was efficient in to increase performances in earlier times of surviving. This means that CSPG removing opens plastic window in ischemic injuries, without influence in injury size or number of astrocytes in glial scar, but with functional increment. New studies have to be done, associated ChABC to supporting therapies in ischemic injuries treatment.
Acesso aberto (Open Access)
Modulação da neuroinflamação celular e neuroproteção induzidas por tratamento com betacariofileno em um modelo experimental de isquemia estriatal em ratos adultos
(Universidade Federal do Pará, 2016-10-11) LOPES, Rosana Telma Santos; SANTOS, Enio Maurício Nery dos; http://lattes.cnpq.br/7789458294239924; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke results from the transitory or permanent reduction of cerebral blood flow. It can be classified as hemorrhagic or ischemic. Ischemic stroke is responsible for around 87% of all cases. This acute neural disorder is the second cause of mortality and disability around the world and the main cause of death in Brazil. Since ischemic stroke in patients usually results from a thrombotic or embolic occlusion of the middle cerebral artery (MCA), experimental models of ischemia have been developed to mimic human stroke. There are no neuroprotective drugs available for human stroke. It follows that research on development of alternative neuroprotective drugs are of important clinical relevance. In this study, we investigated the effects of betacaryophyllene, the main sesquiterpene present in about 40% of the copaiba oil-resin composition, on microglial activation, astrocytic reactivity and neuronal preservation following experimental MCAO in adult rats. Animals were submitted to experimental stroke by microinjections of endothelin-1 (ET-1) and treated (i.p) with betacaryophillene (N=4) or vehicle control (N=4) and perfused at 3 days or 7 days post-MCAO. Gross histopathology was performed using cresyl violet staining. Immunohistochemistry was used to assess neuronal loss (anti-NeuN), microglial activation (anti-ED1) and astrocytosis (anti-GFAP). Numbers of NeuN+ and GFAP+ cells were quantified in the ischemic striatum. Betacaryophyllene treatment reduced microglial activation, increased neuronal preservation and decreased astrocytic reactivity at 7 days post-MCAO. These results suggest that betacaryophylene modulates neuroinflammation and is neuroprotective following experimental striatal. Considering that betacaryophyllene is a natural dietetic extract already used in non-neural human diseases with antiinflammatory, anti-microbial and anti-carcinogenic properties, its use as a neuroprotective agent is a promising future therapy for human stroke.
Acesso aberto (Open Access)
Neurogênese endógena induzida por acidente vascular encefálico experimental após inibição da ativação microglial/macrofágica com o anti-inflamatório indometacina
(Universidade Federal do Pará, 2011-05-16) LOPES, Rosana Telma Santos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke results from the transitory or permanent reduction of cerebral blood flow. It can be classified as hemorrhagic or ischemic. Ischemic stroke is responsible for around 87% of all cases. This acute neural disorder is the second cause of mortality and disability around the world and the main cause of death in Brazil. It has been shown that neuroblasts migrate to the ischemic striatum following middle cerebral artery occlusion (MCAO) and partially replace neurons lost during ischemia. Nevertheless, most of the migrating neuroblasts die in the first weeks following MCAO and inflammatory events, mainly microglia activation, may underlie neuroblast death. In this study, we investigated the effects of the nonsteroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and adult neurogenesis following experimental MCAO in adult rats. Animals were submitted to endothelin-1 induced- MCAO and treated (i.p) with indomethacin (N=8) or sterile saline (N=8) for 7 days and perfused at 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1 and ED1) and migrating neuroblasts (anti-DCX). The numbers of NeuN, ED1 and DCX positive cells per field were counted in the ischemic striatum or subventricular zone. Indomethacin treatment reduced microglial activation in general and the number of ED1+ cells at both 8 and 14 days (±6,9 and ±3,0 cells respectively) postinjury, compared to control (±7,9 or ±6,5 cells, p<0.001, ANOVA-Tukey). There was an increase in the number of DCX+ cells in both subventricular zone (SVZ) and striatum at the same survival times. There was no difference in the number of NeuN positive cells between groups in all investigated survival times. The results show that indomethacin treatment induces inhibition of microglial activation concomitant with increased neuroblast proliferation and migration following MCAO. This is a promising outcome, considering that indomethacin is already used in non-neural human diseases and that adult neurogenesis may underlie functional recovery following stroke.
Acesso aberto (Open Access)
Teste de equivalência e exame eletrofisiológico em pessoas acometidas por acidente vascular cerebral com e sem comprometimento cognitivo.
(Universidade Federal do Pará, 2017-01-27) PARANHOS, Alna Carolina Mendes; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; https://orcid.org/0000-0002-4525-3971; PARACAMPO, Carla Cristina Paiva; http://lattes.cnpq.br/9018003546303132
Stroke is a neurological dysfunction caused by an abnormality in the cerebral circulation. About 30% of the victims will present cognitive impairment three months after the injury and 10% some type of dementia. In the area of Neuroscience and Behavior, studies have suggested that the N400 component is activated both in semantic choice tasks and in equivalence tests. The present study aimed (1) to study the learning of conditional relations and equivalence test in stroke survivors with and without cognitive impairment and (2) to verify the occurrence and quality of the N400 component in diferent stimuli conditions with the presentation of equivalent and non-equivalent pairs, before and after training of conditional relations and equivalence test. Eighteen participants (nine in each study) distributed into three groups - Control Group (GC), composed of healthy adults; And two Experimental Groups, stroke patients without cognitive impairment (GE1) and patients with cognitive impairment (GE2). In Study 1, all participants were exposed to a training structure of arbitrary conditional relations AB, AC and AD, and subsequent equivalence test. Study 2 was identical to Study 1 regarding the conditional teaching protocol used, the difference was in the event-related potential records in the participants, before and after the equivalence method. The results of Study 1 and 2 suggest that the teaching protocol used was effective in establishing arbitrary conditional relations and equivalence classes for GC and GE1 participants but not effective for participants in GE2. In Study 2, the occurrence of the N400 component was ob served in the four stimulation conditions in the event-related potential records of the Participants P21 (GC), P23 (GC) and P24 (GE1), in the Participant P26 (GE1) in three stimulation conditions and in Participants P27 (GE2) and P29 (GE2) in none of the four stimulation conditions. The results suggest a direct relation between the degree of learning of conditional relations and the formation of equivalence classes with the occurrence and quality of the N400 component. The present study extends the analyzes of this correlation when conducting the experiments with a population of stroke, with and without cognitive impairment, having great applicability in the context of cognitive evaluation and rehabilitation.
Acesso aberto (Open Access)
Tratamento com minociclina e transplante intraestriatal de células mononucleares da medula óssea após acidente vascular experimental encefálico
(Universidade Federal do Pará, 2011-04-27) SILVA, Michelle Castro da; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Several studies suggest that both the semi-synthetic tetracycline minocycline and mononuclear bone marrow cell (BMMCs) transplantation induce neuroprotection in experimental models of stroke. However, a few studies comparatively investigated the effects of these therapeutic approaches following endothelin-1 (ET-1)-induced stroke. In this dissertation, we aimed at investigating the comparative effects of microglial inhibition with minocycline and BMMC transplantation in the acute phase of experimental stroke. Male adult Wistar rats were divided in four experimental groups: saline-treated (N=4), minocyclinetreated (N=4), BMMC-treated (N=4). Behavioral tests were performed at 1, 3 and 7 days post-ischemia to evaluate functional recovery between groups. Animals treated with minocycline received two 50mg/kg (i.p.) doses in the first two days plus five single 25mg/kg (i.p.) daily doses up to sixth days post-ischemia. 1x106 BMMCs were obtained from Wistar rats and directly transplanted into the striatum at 24h post-ischemia. Animals were perfused at 7 days after ischemia onset. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1) and apoptotic cells (active caspase-3). Gross histopathological analysis revealed pallor, tissue loss and intense microglial/macrophage activation in ischemic animals treated with sterile saline. BMMC transplantation induced a higher reduction (p<0.05, ANOVA-Tukey) in the number of ED1+ cells than (saline, 276, 3± 9,3;BMMCs, 133,8± 6,8; minocycline, 244,6 ± 7,1). BMMC transplantation and minocycline reduced the infarct area, compared to control, in about 67,75% and 69,1%, respectively, with no statistical differences between treatments (p>0.05). Both treatments afforded comparable levels (p>0.05) of neuronal preservation compared to control (61,3± 1,5; 86,8± 3,4; 81±3,4). BMMC treatment induce a higher decrease in the number of apoptotic cells compared to control and minocycline treatment (26,5± 1,6; 13,1± 0,7; 19,7± 1,1). Both therapeutic approaches improved functional recovery in the ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation. Future studies should investigate whether minocycline treatment concomitant with BMMC transplantation produces synergistic effects, which might improve neuroprotection.