RESUMO
OBJECTIVES: This study aimed to investigate the possible modification of the neuroprotective effect of sodium ferulate, when orally co-administered with borneol, in transient global cerebral ischaemia-induced functional, histological and cellular alterations in mice. METHODS: The bilateral common carotid artery occlusion was conducted in C57 BL/6J mice for 25 min. The mice were then subjected to a water maze test over an extended recovery period, followed by an assessment of neuronal loss in the CA1 region of the hippocampus (haematoxylin and eosin staining). The blood-brain barrier permeability (Evans blue tracing), brain oedema and oxidative stress were assayed and histological sections were also immunostained for gliofibrillar acid protein (GFAP) expression. KEY FINDINGS: The ischaemia reperfused mice were associated with long-lasting spatial learning deficits in the absence of other behavioural impairments and with neurodegeneration in the hippocampal CA1 region. However, the histological injuries were significantly attenuated by oral co-administration of sodium ferulate and borneol. Furthermore, combined treatment with sodium ferulate and borneol resulted in a significant reduction in brain oedema, GFAP-positive cells, malonaldialdehyde levels and blood-brain barrier permeability, but an increase in superoxide dismutase activity. CONCLUSIONS: Borneol may have benefits for the neuroprotective effect of sodium ferulate against injury induced in the brain by ischaemia/reperfusion.
Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Canfanos/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Canfanos/administração & dosagem , Canfanos/farmacologia , Artérias Carótidas , Transtornos Cerebrovasculares , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/farmacologia , Quimioterapia Combinada , Edema/tratamento farmacológico , Proteína Glial Fibrilar Ácida , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/patologia , Aprendizagem , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Permeabilidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismoRESUMO
The relationship between cerebral ischemia and Alzheimer's disease has been evaluated extensively. However, the association between cerebral ischemia and the deposition of beta-amyloid (Abeta) remains to be clarified. Here, we used mice bilateral common carotid artery ligation model to investigate the alterations in mRNA expression of Abeta precursor protein cleavage enzyme 1(BACE1), cathepsin B, and glutaminyl cyclase after transient global cerebral ischemia. The reverse-transcriptase PCR assay showed that the expressions of these three Abeta-metabolism-related genes were upregulated in brain with different manner. It indicates that all these three Abeta-metabolism-related genes may participate in the acute and chronic Abeta generation after transient cerebral ischemia, and will be helpful to understand the mechanisms underlying the linkage of brain ischemia and Alzheimer's disease.