Navegando por Assunto "Endotelina-1"

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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)
Ajustes motores compensatórios após lesão isquêmica focal unilateral do trato corticoespinhal
(Universidade Federal do Pará, 2017-06-30) CARVALHO, Walther Augusto de; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170
The aim of this work was to develop a new model of spinal cord injury caused by focal and unilateral transient ischemia after ET-1 microinjection in the dorsal funiculus and to evaluate the sensorimotor alterations of the anterior paw of rats (Wistar). Fifty (n = 50) animals (CEPAE / UFPA protocol BIO007912), who were trained, thirty-three (n = 33) were selected to compose control (n = 15), sham (n = 6) and injury (n = 12) groups. By using a micropipette, we injected the volume of 250 nL of saline (sham) or endothelin-1 (lesion) near the medial dorsal artery of the cervical segment C4 at a depth of 1 mm from the pial surface of the spinal cord. ET-1 induced cystic cavity formation of 0.421 mm2 (± 0.035 mm2, n = 3) on the corticospinal tract and suprajacent white matter, ipsilateral to the microinjection site that can be measured in cross-sections (50 μm) stained by the Nissl technique. The motor functions of the forepaw were evaluated by specific sensorimotor tests before and after injury at 3, 7 and 14 days. The results were evaluated by the ANOVA statistical test with Tukey post-hoc analysis (α = 0.05). Our results show in pasta test that after injury there is a compensatory motor behavior in which the non-preferential forepaw assumes the functions of the preferential forepaw. The Staircase test revealed a decrease in the ability to grasp the object with the preferred paw and the Contact test showed a decrease in sensitivity of the preferred paw.
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 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)
Perda neuronal, ativação glial, neurogênese e alterações sensório-motoras após isquemia focal no córtex somestésico de ratos adultos
(Universidade Federal do Pará, 2012-09-26) CORRÊA, Vania Castro; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke is considered one of the most important causes of death and functional deficits in the world. Few neurological conditions are so complex and devastating, resulting in severe neurological deficits and death in the survivors. The cortical regions are commonly affected by stroke, resulting in sensory and motor loss. The establishment of neuropathological patterns in cortical regions, including the somatosensory area, is critical for the investigation of possible therapeutic interventions. In the present study, we investigated the patterns of neuronal loss, microgliosis, astrocytosis, neurogenesis and functional deficits in the primary somatosensory cortex of adult rats submitted to focal ischemia induced by microinjections of 40 pmol of endothelin-1 (ET-1). A total of 30 young adult Wistar rats (Rattus norvegicus) of Wistar, weighing between 250-280g were used in the study. The animals were divided into ischemic (N = 21) and control (N = 9) groups. They were perfused at survival times of 1, 3 and 7 days. The 7 days animals were submitted to behavioral tests to evaluate sensorimotor impairment. Sections were stained with cresyl violet, cytochrome oxidase and immunostained to identify neurons (anti-NeuN), activated and non-activated microglia (Iba-1), activated macrophages/microglia (ED-1), astrocytes (GFAP) and neuroblasts (DCX ). Statistical comparisons between groups were made by one analysis of variance (ANOVA) with Tukey post-hoc test. The animals showed ischemic sensorimotor deficits revealed by Bederson Neurological Scale, Paw Placement and corner tests. Microinjections of ET-1 induced focal ischemic lesion in the primary somatosensory cortex with neuronal loss and progressive astrocytosis and microgliosis mainly in the late survival times. The cytochrome oxidase histochemistry revealed the barrel fields, but unexpectedly marked a population of inflammatory cells with macrophage characteristics in the ischemic region. Increased numbers of SVZ neuroblasts were observed mainly in late survival times of ipsilateral hemisphere in comparison to contralateral side and control animals. There was no significant migration of neuroblasts to the ischemic cortex. The results show that microinjections of ET-1 are an effective method for inducing tissue loss and sensorymotor deficits in the primary somatosensory cortex of adult rats. It was evident that the SVZ is influenced by distant ischemic events distant and that macrophage populations seem to increase the cytochrome oxidase expression. The implemented experimental model can be used in future studies, in which potential neuroprotective drugs can be tested to minimize the described neuropathological alterations.