Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2375

O Mestrado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).

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Acesso aberto (Open Access)
Análise in vitro do potencial antitumoral do conjugado LDE/Paclitaxel comparado à formulação do comercial Taxol sobre linhagem celular C6 de glioblastoma de rato
(Universidade Federal do Pará, 2022-09) ANJOS, Ana Carolina Brito dos Anjos; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; https://orcid.org/0000-0003-2909-949X; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Glioblastoma, also known as grade IV astrocytoma, is one of the most common and aggressive types of tumors in the central nervous system. Among the characteristics of this type of tumor, the following stand out: infiltration of isolated tumor cells in normal brain tissue, cell proliferation, angiogenesis and intense necrosis. Currently, the main therapeutic approach consists of surgical resection followed by radiotherapy and chemotherapy. However, in most cases, the tumor is not well defined, spreading through the brain region, which makes it difficult to fully resection. In addition, the removal of tissue from this region can leave several sequels. Consequently, patients have high rates of recurrence and low rates of survival. Another problem in the treatment of this type of tumor is due to the lining of the blood-brain barrier that restricts the entry of molecules and substances, including drugs. Thus, this project aims to analyze the antineoplastic effects of the association of a nanoparticle called LDE with a structure similar to low-density lipoprotein (LDL) that will act as a carrier of the drug paclitaxel (PTX), commercially known as Taxol®, it is a chemotherapeutic drug whose cell antiproliferative action has been proven in the treatment of other types of cancer, such as breast and refractory ovarian cancers. For this purpose, the mouse glioblastoma cell line C6 was used for performing in vitro analysis regarding the effects of these treatments on aspects of viability, cytotoxicity and cell death by apoptosis, using the ApoTox-GloTM Triplex Assay kit (Promega Corporation), which performs the three previously mentioned analyses, sequentially. To evaluate growth and drug effect on PTX and LDE/PTX treatment groups, approximately 1x106 cells were cultured in 96-well microplates at concentrations of 0.01; 0.1; 1 and 10 μM in the times of 24h, 48h and 72h. The control was not exposed to the compounds, containing only DMEM culture medium. Results obtained after treatments with PTX and LDE/PTX were expressed as mean ± standard deviation and analyzed by one-way (cytotoxicity) and two-way (viability and apoptosis) ANOVA, followed by Tukey's post hoc test. Differences were considered significant when p ˂ 0.05.
Acesso aberto (Open Access)
Ativação microglial, perda neuronal e astrocitose em um modelo experimental de epilepsia do lobo temporal
(Universidade Federal do Pará, 2011-05-12) FERREIRA, Elane de Nazaré Magno; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Epilepsy is one of the most prevalent serious chronic neurological conditions worldwide. The World Health Organization (WHO) estimates 45-50 cases in 100,000 habitants in developed countries, rising to 122 to 190, in developing countries, including Brazil. There are no risk factors in relation to gender, race or age, but it is believed that some gene mutations are associated with an increased risk to develop the disease. The pathophysiology of epilepsy involves complex factors such as loss inhibition and increased neuronal excitability in different brain regions, but mainly at the hippocampus. Mutations in ion channels and in both receptor and neurotransmitter transporters may underlie disease pathogenesis. The inflammatory response plays an important role on epilepsy pathophysiology. Recent experimental evidence suggests a major role for both microglia and astrocyte activation on the seizure exacerbation. In this dissertation, we describe the general patterns of microgial and astrocyte activation and neuronal loss in CA1, CA3, hippocampal hylus, peririnal, lateral entorrinal and motor cortices and amigdaloid complex in the first week following “Status Epilepticus” induced by pilocarpine injection. Immunohistochemistry was performed to label neurons (anti-NeuN), microglia in general (anti-Iba1), activated microglia/macrophages (anti-ED1) and astrocytes (anti-GFAP). Numbers of neurons and activated microglia were counted in the hippocampus. There was intense microglia and astrocyte activation in all motor and limbic regions studied, mainly at 3 and 7 days post SE. Minocycline treatment reduced microglia activation in the hippocampus (p<0.05), without affecting astrocytosis. There was considerable inflammation in regions outside the hippocampus with an early inflammatory response. There was no neuronal loss in the hippocampus in the first week following SE, although sporadic alterations on neuronal morphology have been observed. These results suggest that the inflammatory response is an early and generalized histopathological event in several motor and limbic structures following pilocarpine-induced SE, even in the absence of conspicuous cell loss. The patterns of microglia and astrocyte activation can be used as markers of the progressive tissue impairment in the experimental models of epilepsy.
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)
Avaliação neuropatológica da lesão estriatal em ratos machos e fêmeas da linhagem lister hooded induzida experimentalmente por microinjeções de endotelina-1
(Universidade Federal do Pará, 2012-05-30) SANTOS, Ijair Rogerio Costa dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
The inflammatory response may exacerbate the process harmful after acute neural disorders. Sexual dimorphism generated by different hormonal attendance between male and female have demonstrated neuroprotective abilities endogenous opposite, showing a better preservation of the integrity of the nervous tissue in female, putatively due to the presence of gynoid hormones. However, there is no research work comparing how this difference might affect the inflammatory response during stroke. In the present study, we investigated the differences in acute inflammatory processes of sexual dimorphism in adult rats of both sexes subjected to acute ischemic injury induced by endothelin (ET1) in the striatum. Six experimental groups were designed: male animals survival 24 hours (n = 8); male survival of 72 hours (n = 8); male survival of 7 days (n = 8) and female 24 hours survival (n = 8), females 72 hours of survival (n = 8); female seven days of survival. Histopathologic analysis was performed in the general sections stained with violet cresila. Macrophages, astrocytes, and neurons were identified by immunohistochemistry with antibodies specific for these inflammatory cells (ED1, anti-GFAP and Anti-NeuN, respectively). We conducted counts activated microglia / macrophages and neuron bodies mentioned in the experimental groups. No difference was observed quantitatively between different sexes, but there was an apparent decrease in the amount of macrophages / microglia at 3 days but in males and in females, presenting apparently some difference in the activation of astrocytes was stronger in males. The results suggest that sex differences, at least in lineage Lister hooded is not enough to cause significant differences in the preservation of nerve tissue and in some aspects of the inflammatory response after induction of cerebral ischemia by ET1.
Acesso aberto (Open Access)
Efeitos anti-inflamatórios e neuroprotetores do extrato de cipó-pucá (Cissus verticilata) após lesão aguda da medula espinhal de ratos adultos
(Universidade Federal do Pará, 2019-02-15) LIMA, Kelly Correa; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Acute spinal cord injury (aSCI) is a serious pathological condition that affects several individuals in different regions of the world and may cause physical and/or psychological sequelae. The available treatment is ineffective, which demands on development of new therapeutic approaches. The development of neuroprotective agents is of fundamental importance for the tissue preservation after aSCI. In the Amazon rain forests there are a multitude of medicinal plants, whose potential anti-inflammatory and neuroprotective effects have not been investigated. Cipó-pucá (Cissus verticillata) is used for treatment of stroke in folk medicine, but its effects are not scientifically proven and have not been investigated after aSCI. In this study, we investigated the anti-inflammatory and neuroprotective effects of the supercritical extract of cipó-pucá in an experimental model of aSCI in adult rats. The extracts of leaves of cipó-pucá were obtained by extraction with supercritical fluid. The animals underwent partial hemisection surgery of the spinal cord and were treated with extract of cipó-pucá (50 mg / kg) or vehicle. They were perfused at 24 hours postinjury. The gross histopathology was performed by hematoxylin-eosin staining. Immunohistochemical analysis for visualization of neurons, microglia, astrocytes and neutrophils were performed using antibodies against NeuN, CD68, caspase-3 and MBS-1, respectively. The quantitative analysis showed neuronal preservation and, reduction of the apoptotic cells, activated microglia and inflammatory infiltrate (neutrophils) in treated animals compared to the control group, suggesting a neuroprotective and anti-inflammatory effect of the supercritical extract of cipó-pucá in the aSCI model.
Acesso aberto (Open Access)
Efeitos anti-inflamatórios e neuroprotetores do extrato de cipó-pucá (Cissus verticillata) após isquemia focal induzida por microinjeções de endotelina-1 (ET-1) no córtex motor de ratos adultos
(Universidade Federal do Pará, 2018-12-19) COSTA, Jonabeto Vasconcelos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
The inflammatory response may exacerbate the damaging process after acute neural disorders such as in stroke. Alternatives to obtain a decrease in the inflammatory response in the encephalic cell accident have been widely studied with the use of herbal compounds, in this hypothesis the pucá cucó (Cissus verticillata), an Amazonian medicinal plant popularly used as anti-inflammatory and antihyperglycemic used by folk medicine in the treatment of acute inflammatory diseases. However, there are no investigations into the possible anti-inflammatory and neuroprotective effects of plant extract in experimental models of acute neural disorders. In this study, we investigated the anti-inflammatory and neuroprotective effects of plant extract by supercritical extraction in adult rats submitted to acute injury induced by endothelin-1 (ET-1) in the motor cortex. Two experimental groups were delineated: the first with animals of the control group with a survival time of twenty-four hours and seven days (Group N = 3 for each survival time), submitted to focal ischemia with ET-1, but injected 5% tween intraperitoneal (ip), and the second group of animals treated with doses of 100 mg / kg (ip) of plant extract after surgery with the same survival times (Group N = 5 for each survival time). Then perfused twenty four hours and seven days after induction of ischemic injury. General histopathological analysis was performed in sections stained by cresyl violet and hematoxylin. Neutrophils and macrophages were identified by immunohistochemistry with specific antibodies (anti-MBS1 and IBA-1, respectively), astrocytes labeled with anti-GFAP antibody. Activated microglia/ macrophages and neuronal bodies were counted in the mentioned experimental groups and the astrocyte activity after the lesion was evaluated. Treatment with Cissus verticillata extract induced anti-inflammatory and neuroprotective effects in treated animals, as well as decreased tissue cavitation, astrocyte activation at the center of the lesion and decreased infiltration of polymorphonuclear and/or microglia/ macrophage inflammatory cells.
Acesso aberto (Open Access)
Efeitos neuroprotetores e anti-inflamatórios do óleo de copaíba (Copaifera reticulata Ducke) em ratos adultos submetidos a isquemia do córtex motor por microinfecções de Edotelina-1
(Universidade Federal do Pará, 2019-02-15) SILVA, Paulo Rodrigo Oliveira da; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke is a neural disorder caused by interruption of blood flow in vessels that irrigate the brain (ischemic stroke) or rupture of these (hemorrhagic stroke), causing cognitive, sensory and / or motor deficits. With the exception of thrombolytic use, which has a very narrow therapeutic window and is little used, there are no other pharmacological treatments or cellular therapy available for this pathological condition. Thus, it is necessary to search for new treatments, such as the development of neuroprotective agents. The Amazon is a rich source of natural products, but its therapeutic actions for diseases of the central nervous system (CNS) have been little investigated. In this work, we have investigated the neuroprotective and anti-inflammatory actions of copaiba oil-resin (COR). Adult Wistar rats were submitted to focal ischemia by microinjections (80pMol/μl) of endothelin-1 (ET-1) directly into the motor cortex and were treated with daily doses of COR (400mg / kg) or 5% tween. The animals were perfused at 7 days after the injury. The histopathological analysis was performed by Nissl staining (brain) and hematoxylin-eosin (liver and kidneys). Immunohistochemistry was performed for labeling of neurons (anti-NeuN), astrocytes (anti-S100) and caspase (anti-caspase-3). Morphometry showed a reduction in the lesion size area (copaiba-treated animals (15.96 ± 1.53 mm2); control animals (28.82 ± 2.65 mm2). Histopathological examination of the liver and kidneys did not find changes indicative of toxicity. In the quantitative analysis, neuronal preservation was observed, but no statistical difference was noticed between the groups regarding astrocytes analysis (S100+ cells). The COR-treated group showed an increase in caspase-3 expression. It is concluded that COR may play a neuroprotective role, contributing to neuronal survival in the area of ischemic penumbra, but future work is needed to find out the mechanisms underlying this phenomenon.
Acesso aberto (Open Access)
Fenótipos microgliais e tratamento com minociclina após isquemia focal induzida por microinjeções de endotelina-1 no córtex motor de ratos adultos
(Universidade Federal do Pará, 2016-12-23) DIAS, Michelle Nerissa Coelho; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Microglial cells are fundamental components of the innate immune system that continually make a complete scan of the neural parenchyma in search of subtle tissue changes for the preservation of tissue integrity. These resident macrophages of the central nervous system (CNS) correspond to about 20% of the encephalic cell population. In acute and chronic neural disorders, including brain and spinal cord injury, experimental stroke, Alzheimer's, Parkinson's and Huntington's disease, microglial cells are activated, which is reflected in morphological and biochemical changes. In these diseases, it is believed that microglial activation contributes to both neuroprotection and exacerbation of the injury process. Several experimental evidences suggest that excessive microglial activation may contribute to the increase of the injury process after experimental stroke. However, our previous studies suggest that microglial cells may release trophic factors after experimental stroke in anatomically distinct regions of the microglial population with deleterious phenotypes. There are no studies that have described the reactivity patterns of the different microglial phenotypes after experimental ischemia. In the present project, we will investigate the patterns of activation of microglial cells presenting beneficial and harmful phenotypes, evaluating which microglial populations are inhibited by tetracycline minocycline after focal cortical ischemia. The animals were submitted to focal ischemia in the motor cortex by microinjections of 80 pMol of endothelin-1 (ET- 1). They were sacrificed 7, 14 and 30 days after ischemic induction. The immunohistochemistry technique for the observation of neuronal loss (NeuN +) and double immunofluorescence to evaluate the density of M1 and M2 microglial cells in the lesioned area was used. Statistical analysis of NeuN+ cell density was performed by the Student's t-test from the 7-day of control and treated groups while the analysis of the M1 and M2 microglial cells were done by the analysis of variance in the 07, 14 and 30 control groups, adopting in all tests the level of significance P <0.05. A preservation in the number of neurons in the injured parenchyma of the animals treated with minocycline was confirmed. A decrease in the number of M1 microglial cells in minocycline-treated animals was observed, suggesting that the drug may present effects on expression pathways of M1 microglial phenotypes. However, when the animals of the control group of 07, 14 and 30 are compared, there is an increase in the number of this M1 phenotype that extends from day 7 to day 30. We conclude that there is a neuroprotective effect of the drug minocycline when associated to stroke, suggesting that this drug may be involved in the modulation of microglial phenotypes requiring further studies on its function in the pathways of expression of these phenotypes.
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)
Neuroproteção, diminuição do infiltrado de neutrófilos e microgliose após tratamento com óleo-resina de copaifera reticulata ducke em um modelo experimental de lesão aguda da medula espinhal
(Universidade Federal do Pará, 2017-01-25) SANTOS, Thayssa Ferreira dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Most central nervous system (CNS) diseases are incurable and extremely debilitating, acute spinal cord injury (LAME) causes permanent loss of neurological function below the level of the injury, causing severe physical consequences to patients. Trauma, falls and gunshot or joint weapon damage together make up almost 100% of the main mechanisms that cause LAME, as well as contribute to the high costs of the public health system. The pathophysiology of LAME involves complex processes such as vascular changes, excitotoxicity, lipid peroxidation and neuroinflammation, generated mainly by microglial cells. Despite the knowledge of pathophysiology, there is still no effective treatment for LAME. Thus, there is a mobilization of the scientific community to find a substance capable of promoting neuroprotection and, consequently, to reduce the sequelae of LAME below the level of the lesion. In this context, the Copaíba Resin Oil may represent a good therapeutic strategy. In this study, we investigated the antiinflammatory and neuroprotective effects of copaiba resin oil after hemisection of the spinal cord of rats. The animals were divided into experimental and control groups. Immunohistochemical techniques using anti-MBS-1 (neutrophil marker), anti-Iba-1 (microglial marker) antibodies, as well as staining with Cresila Violet were used. Qualitative and quantitative analyzes were performed. Copaiba resin oil proved effective in decreasing the recruitment of inflammatory cells to the area of spinal cord injury and promoted better preservation of the tissue area compared to the control group. As in the lowest neutrophil recruitment in treated rats compared to the control group (Treated group: 8.33 ± 0.66 (N = 3); Control group: 12.27 ± 0.28 (N = 3)) . Copaíba resin oil also promoted a reduction in the number of microglia in the area of spinal cord injury at different times (Treated group on day 1: 8.59 ± 1.72 (N = 3), Control Group on day 1: 35, (N = 3), Control Group on the 7th day: 65.77 ± 6.19 (N = 3)). These results suggest the antiinflammatory and neuroprotective effect of copaiba resin oil after LAME, revealing a promising strategy for the patient after LAME.
Acesso aberto (Open Access)
Padrões neuropatológicos nas substâncias branca e cinzenta revelados por tomografia computadorizada ou ressonância magnética e déficits neurológicos correspondentes em crianças e com encefalopatia crônica não progressiva da infância
(Universidade Federal do Pará, 2013-01-17) TEIXEIRA, Madacilina de Melo; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
The Chronic non-progressive encephalopathy of the childhood (CNEC) the sequel is more neurological motor impairment for the child, and remains today a perinatal hypoxic-ischemia a major cause of brain injury. It is popularly known as Cerebral Palsy, being defined by a sequel of aggression brain, mainly characterized by a persistent disorder, but not invariable tone, posture and movement, which appears in early childhood. The characterization of this syndrome is done considering the anatomical, etiological, semiological and not evolutionary. In this study we adopted the classification based on anatomical and clinical aspects, emphasizing the symptom engine as the main component of the clinical picture. Neuroimaging has fundamental importance for the diagnosis and prognosis of brain lesions, performing the important function to discard or confirm the presence of lesions in newborns and children with developmental disabilities. Cerebral tomography (CT) and Magnetic Resonance Imaging (MRI), has played a huge role in the study of various tissues that make up the nervous system. Thus this study aimed to assess the neuropathological patterns in white and gray matter, obtained by CT or MRI Skull, in patients with a history of perinatal hypoxicischemic CNEC, correlating the data obtained by neuroimaging with motor patterns obtained by clinical-neurological examination. Current regulations were obeyed to study in humans imposed by Resolution 196/96, submitted to the Ethics Committee and Research of Brazil Platform under Nº 112168. The study population consisted of patients aged zero to seven years, of both sexes, in the Cerebral Palsy ambulatory of Projeto Caminhar of Hospital Universitário Bettina Ferro de Souza (HUBFS), diagnosed with CNEC. The study sample consisted of 15 children diagnosed with CNEC by neonatal hypoxia. For the radiological diagnosis were used in neuroimaging data from reports of CT and MRI of skull. The clinical and neurological evaluation used to assess the movement's model range Gross Motor Function Classification System (GMFCS E & R), developed by Palisano, which grades the child on five levels in which the Level I represents normality and Level V the largest severity of limitation. Of the 15 children assessed for movement and the relationship of the level by motricity GMFCS E & R, 05 children had level V, 04 children level IV, 05 children level III and 01 child level II. As for brain imaging performed 46% TAC and 54% RM Skull. MRI of skull presented in this study as the image of choice because of the 8 children who were examined, 6 had abnormal. It was evident that the imaging study of choice for the child who has Chronic non-progressive encephalopathy of the childhood is the RM of Skull and may be adopted as the protocol for the diagnostic conclusion, avoiding exposing the child to a high load of RX as in TAC, and also avoiding unnecessary spending on public health.
Acesso aberto (Open Access)
Redução do volume hipocampal, perda neuronal e alterações gliais em ratos expostos cronicamente ao etanol da adolescência à fase adulta
(Universidade Federal do Pará, 2013-03-04) OLIVEIRA, Ana Carolina Alves de; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
O consumo de etanol (EtOH) é considerado um problema de saúde pública do Brasil e no mundo, sendo alvo de pesquisas epidemiológicas e de seus efeitos no organismo durante as várias etapas do desenvolvimento humano. Neste contexto, torna-se necessário o entendimento dos efeitos do EtOH no Sistema Nervoso Central, mais especificamente sobre a formação hipocampal, pois embora seja conhecida como uma estrutura particularmente sensível aos seus efeitos deletérios do EtOH, os mecanismos subjacentes aos efeitos de exposição crônica são pouco estabelecidos. O presente estudo objetiva verificar quais as repercussões da exposição crônica ao EtOH em ratos, desde a adolescência até a idade adulta, sobre os padrões morfométricos e morfologia hipocampal. Ratos Wistar, fêmeas, receberam EtOH por gavagem (6,5 g/kg/dia, 22,5% V/v), do 35º ao 90º dia pós-natal, sendo comparado com grupo controle, o qual recebeu apenas água destilada. Foi realizada análise morfométrica e estereológica, bem como histoquímica e imunoistoquímica. Para a marcação imunoistoquímica, utilizou-se os anticorpos Anti-NeuN, Anti-GFAP e Anti-Iba1. Verificou-se perda neuronal significativa em CA1 e hilo, com CA3, apresentando diminuição não significante no número de células Neu-N+. Também foi encontra redução significativa da população microglial em todas as áreas investigadas, com ativação destas células. Houve redução no número de astrócitos em animais expostos ao EtOH em todas as áreas, embora não de forma significativa em CA1. Análise estereológica evidenciou redução de volume na formação hipocampal de ratos expostos ao EtOH em relação ao grupo controle. Desta forma, conclui-se que animais expostos cronicamente ao EtOH, sofrem redução volumétrica e perdas neuronal e glial na formação hipocampal.
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.

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