Therapeutic neuroprotective effects of XQ-1H in a rat model of permanent focal cerebral ischemia.

Cerebral ischemia is one of the leading causes for death and severe disabilities in the world. XQ-1H exerts neuroprotective effects under various neurotoxic conditions in vitro. In vivo, it reduces brain damage after transient focal cerebral ischemia. The present study evaluated the dose effectiveness and therapeutic time window of neuroprotection of XQ-1H by behavioral and histological measures in rats subjected to permanent middle cerebral artery occlusion (pMCAO). Neurological deficits, TTC stain, brain water content, necrosis neuron counts, and Evans-Blue extravasation were used to quantify brain damage and blood-brain barrier dysfunction. Our results demonstrated that postischemic treatment with XQ-1H at a dose of 31.2 mg/kg produced a significant reduction in neurological scores when treatment was initiated within 2 h of pMCAO. A similar improvement was also observed in infarct volume, brain water content, Evans-Blue extravasation, and neuronal necrosis when treatment was initiated within 1 h of pMCAO. Treatment with XQ-1H at the dose of 15.6 mg/kg within 1 h also produced significant improvement in ischemia deficit. In conclusion, the therapeutic time window of XQ-1H extends for up to 1 h after pMCAO, and treatment with XQ-1H exhibits potent neuroprotection that may be of value for the design of stroke therapies.