Repercussão cerebral após um insulto isquêmico no roedor neotropical Proechimys

• Ano de defesa: 2019
• Autor(a) principal: Villatoro, Nancy Nohemi Ortiz [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Proechimys; Thrombosis; Inflammation; Stroke; Electrophysiology; Acidente Vascular Cerebral; Trombose; Inflamação; Eletrofisiologia
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=8001328; https://repositorio.unifesp.br/handle/11600/59958

Stroke is a serious public health problem with a limited treatment option and narrow therapeutic window and therefore available only to about 5% of patients. It is the second leading cause of death worldwide and, in addition to its high incidence and high mortality rates, stroke is highly disabling. Approximately 87% of all cases correspond to ischemic stroke. This work strengthens the usefulness of investigating the responses elicited by induced brain injury in a non-conventional animal model, the Proechimys rodent. This exotic wildlife species of the Amazon rainforest seems to have a better restorative mechanism to recover from cortical photothrombotic infarction as compared with the traditional laboratory Wistar rats. Focal cortical photothrombotic stroke was induced in male Proechimys and Wistar rats. Experiments were performed 24-h and 30days after injury. Blood brain barrier (BBB) permeability was assessed by measuring Evans blue extravasation, infarct volume by mitochondrial viability and by stereological estimation of Nissl-stained slices, glial activation by immunofluorescence, brain levels of inflammatory cytokines and growth factors by ELISA, neuronal death estimated by total number of cresyl violet stained neurons. Brain tissue excitability was evaluated by cortical spreading depression phenomenon and by long-term electroencephalographic recordings (EEG). The Proechimys rodent group showed lower blood-brain barrier permeability, smaller volume of ischemic infarction and lesser glial activation than Wistar group. Substantially lower neuronal loss was detected in both perilesional area and ipsilateral thalamus of Proechimys as compared with Wistar. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Differences in cortical electrophysiological features associated with lesion were detected between animal species subjected to spreading depression induction suggesting a lower post-stroke impact in the brain of Proechimys. A major finding of our study is that ischemic injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Our findings highlight singular endogenous antiepileptogenic mechanisms and post-stroke recovery capabilities in Proechimys. As emergent interest in epilepsy research is the understanding of neurobiological processes for preventing post-stroke epileptogenesis or minimizing its effects, Proechimys may prove to be a useful animal model in identifying antiepileptogenic mechanisms to enable the design of disease-modifying approaches.