Olfactory ensheathing cells transplantation attenuates chronic cerebral hypoperfusion induced cognitive dysfunction and brain damages by activating Nrf2/HO-1 signaling pathway

Chronic cerebral hypoperfusion (CCH) has become a crucial factor contributing to neurological disorders and cognitive deficits. Olfactory ensheathing cells (OECs) transplantation has been widely used to repair central nerve systems (CNS) injury, however, whether this intervention has therapeutic effects on CCH-induced cognitive dysfunction and brain damages is still unknown. In this study, we sought to determine the potential therapeutic effects of OECs transplantation on CCH. Two days after the establishment of 2VO rat model, OECs or its medium transplantation were performed via intrastriatal injection. In our study, OECs treatment significantly improved learning and memory in 2VO rats. Transplantation of OECs also significantly reduced brain cell death, neuroinflammation and oxidative stress. Mechanistically, transplantation of OECs increased the expression of nuclear factor-like 2 (Nrf2) and hemeoxygenase 1 (HO-1). Finally, treatment with Brusatol, a Nrf2 inhibitor, markedly abolished the neuroprotective effects of OECs on cognitive decline, oxidative stress, Nrf2 and HO-1 expression. These results demonstrated that OECs transplantation protected CCH-induced cognitive impairment and brain injury by suppressing neuroinflammation and oxidative stress. The activation of Nrf2/HO-1 signaling pathway may contribute to the neuroprotection of OECs transplantation in CCH.