To explore the neuroprotective effect of minocycline on cognitive impairment in a rat model of vascular dementia (VD) and its potential molecular mechanism.

SD male rats were randomly divided into the sham-operation group, vascular dementia group and minocycline treated group. Rats were administered with minocycline by intraperitoneal injection after the surgery of bilateral common carotid artery occlusion. After 28 days, the Morris water maze test was carried out to test the spatial learning and memory ability of rats. The morphological changes of brain were observed by HE staining. Western blot was used to evaluate apoptosis mechanism of rat hippocampal neurons.

(1)Minocycline treatment to VD rats significantly shortened the escape latency compared to the VD rats. In addition, Minocycline treated group spent more time in the target quadrant than the VD rats (P<0.05). (2)HE staining showed that minocycline could obviously protect the hippocampal neurons against damage in VD rats. (3)The protein expression of caspase-3 and Bax/Bcl-2 ratio in the minocycline administration group were significantly lower than those of the VD group (P<0.05). (4)Although minocycline decreased p-GSK-3β expression relatively to the VD group, the protein expression of PI3K and p-AKT in the minocycline treated group was significantly higher than that of the control group (P<0.05).

Minocycline protects against apoptosis of hippocampal neurons via the activation of PI3K/AKT signaling pathway and the inhibition of downstream target protein GSK-3β activity. Minocycline can play an important role in the protection of hippocampal neurons and the improvement of cognitive dysfunction.