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Acta cir. bras ; 36(10): e361002, 2021. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1349867

RESUMO

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major cause of death and disability with a huge economic burden worldwide. Cerebrolysin (CBL) has been previously used as a nootropic drug. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the precise role of necroptosis in CBL neuroprotection following ICH has not been confirmed. Methods: In the present study, we aimed to investigate the neuroprotective effects and potential molecular mechanisms of CBL in ICH-induced early brain injury (EBI) by regulating neural necroptosis in the C57BL/6 mice model. Mortality, neurological score, brain water content, and neuronal death were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Evans blue extravasation, Western blotting, and quantitative real-time polymerase chain reaction (PCR). Results: The results show that CBL treatment markedly increased the survival rate, neurological score, and neuron survival, and downregulated the protein expression of RIP1 and RIP3, which indicated that CBL-mediated inhibition of necroptosis, and ameliorated neuronal death after ICH. The neuroprotective capacity of CBL is partly dependent on the Akt/GSK3β signaling pathway. Conclusions: CBL improves neurological outcomes in mice and reduces neuronal death by protecting against neural necroptosis.


Assuntos
Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Necroptose , Transdução de Sinais , Hemorragia Cerebral/tratamento farmacológico , Apoptose , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neuroproteção , Glicogênio Sintase Quinase 3 beta/farmacologia , Aminoácidos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo
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