Naringenin alleviates cognitive dysfunction in rats with cerebral ischemia/reperfusion injury through up-regulating hippocampal BDNF-TrkB signaling: involving suppression in neuroinflammation and oxidative stress.

Abstract

Cognitive dysfunction is one of the common complications of cerebral ischemia-reperfusion (CI/R) injury after ischemic stroke. Neuroinflammation and oxidative stress are the core pathological mechanism of CI/R injury. The activation of brain derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling antagonize cognitive dysfunction in a series of neuropathy. Naringenin (NAR) improves cognitive function in many diseases, but the role of NAR in CI/R injury-induced cognitive dysfunction remains unexplored. The study aimed to explore the potential protective effects of NAR in CI/R injury-induced cognitive dysfunction and underlying mechanism. The rats were exposed to transient middle cerebral artery occlusion (MCAO) and then treated with distilled water or NAR (50 or 100 mg/kg/day, p.o.) for 30 days. The Y-maze test, Novel object recognition test and Morris water maze test were performed to assess cognitive function. The levels of oxidative stress and inflammatory cytokines were measured by ELISA. The expressions of BDNF/TrkB signaling were detected by Western blot. NAR prevented cognitive impairment in MCAO-induced CI/R injury rats. Moreover, NAR inhibited oxidative stress (reduced levels of malondialdehyde and 4-hydroxynonenal, increased activities of superoxide dismutase and Glutathione peroxidase) and inflammatory cytokines (reduced levels of tumor necrosis factor-α, Interleukin-1β and Interleukin-6), up-regulated the expressions of BDNF and p-TrkB in hippocampus of MCAO-induced CI/R rats. NAR ameliorated cognitive dysfunction of CI/R rats via inhibiting oxidative stress, reducing inflammatory response, and up-regulating BDNF/TrkB signaling pathways in the hippocampus.