Midkine and retinoic acid reduce cerebral infarction induced by middle cerebral artery ligation in rats.

The present study investigates the neuroprotective effects of midkine (MK) and retinoic acid (RA) against ischemia in the CNS. Primary cortical neurons, derived from rat E15 embryos (DIV9), were treated with 9-cis-RA (9cRA), all-trans-RA (atRA) or vehicle. Using quantitative PCR, the level of MK mRNA was significantly increased at 4h after 9cRA application. The protective effect of RA and MK was also investigated in adult Sprague-Dawley rats. 9cRA, atRA, MK, or vehicle was injected into the lateral ventricle prior to a 60-min-MCA ligation. Pretreatment with 9cRA or MK attenuated cerebral infarction in stroke animals. Application of a similar dose of atRA did not reduce the size of infarction. In conclusion, our data suggest that 9cRA has neuroprotective effects against ischemia-related brain injury which may involve upregulation of midkine.