Neuroprotective effects of the ergoline derivative nicergoline following transient and permanent focal cerebral ischemia in rats

Chikako Nito, Yasuhiro Nishiyama, Tomonari Saito, Satoshi Suda, Masayuki Ueda and Kazumi Kimura

Nicergoline has been widely used for various conditions, including cerebrovascular disorders and senile mental impairment. However, the precise mechanisms underlying this neuroprotection remain unknown. We investigated the neuroprotective properties of nicergoline on outcome after focal ischemia in rats. Sprague–Dawley rats were treated with nicergoline or vehicle through a gavage feeding needle for 7 days before the induction of ischemia. For ischemia, rats were subjected to transient middle cerebral artery occlusion (tMCAO) or permanent middle cerebral artery occlusion (pMCAO). Magnetic resonance imaging was used to obtain cerebral blood flow (CBF) measurements at 24 hours after tMCAO and pMCAO. Nicergoline significantly diminished infarct area and edema volume compared with the vehicle-treated group at 24 hours after tMCAO, but there was no significant reduction in behavioral dysfunction. Twenty-four hours after pMCAO, the nicergoline-treated group showed significantly reduced infarcts, edema, and neurological scores compared with the vehicle-treated group. Decreased areas of CBF were markedly smaller in the nicergoline-treated group compared with the vehicle-treated group 24 hours after occlusion in both models. This study shows that pretreatment with nicergoline prevents brain damage, and increased CBF levels may be involved in the neuroprotective mechanism of nicergoline after acute stroke.