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Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen‐activated protein kinase signalling pathway

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Clinical and Experimental Pharmacology and Physiology

Published online on

Abstract

Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague‐Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low‐dose (3 mg/kg) ebselen‐treated group; (iv) a moderate‐dose (10 mg/kg) ebselen‐treated group; and (v) a high‐dose (30 mg/kg) ebselen‐treated group. The TBI model was created according using a modified weight‐drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll‐like receptor (TLR) and phosphorylated (p‐) p38 mitogen‐activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham‐operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose‐dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p‐p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4‐mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI.