Therapeutic time window for treatment of focal cerebral ischemia reperfusion injury with XQ-1h in rats

Pervious experimental studies have shown that XQ-1h has beneficial neuroprotective effect in the cerebral ischemia reperfusion injury. However, the therapeutic time window for treatment of focal cerebral ischemia reperfusion injury with XQ-1h is not clear. Under chloral hydrate anesthesia, transient focal cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Saline as vehicle or XQ-1h at the doses of 31.2, 15.6 and 7.8 mg/kg i.v. was administered at 0.5, 1, 2, 3 h after induction of ischemia. Subsequently, 24 h after MCAO brain edema, infarct volume, neurological deficits and cerebral blood flow were evaluated. Administrations of XQ-1h at the doses of 31.2 mg/kg at 0.5, 1, and 2 h after reperfusion of MCAO significantly reduced infarct rate (%) by 75.6% (5.2 ± 1.7), 66.2% (7.2 ± 1.9), and 47.9% (11.1 ± 1.2), respectively. XQ-1h (31.2 mg/kg) treatment, 0.5, 1, and 2 h after reperfusion produced significant improvement in neurological score compared to vehicle-treated group (P < 0.01). Administrations of XQ-1h at the doses of 31.2 mg/kg and 15.6 mg/kg at 0.5, 1, and 2 h after reperfusion of MCAO significantly increased cerebral blood flow (mv) by 16.9 ± 1.9, 11.7 ± 1.3, 9.5 ± 1.0, respectively (P < 0.01). In conclusion the therapeutic time window of XQ-1h for cerebral ischemia reperfusion injury is within 2 h. Interestingly, we also discovered that the therapeutic time window of XQ-1h is deeply related with the activity of scavenging oxidative stress products. Further studies need to be conducted more drug combination therapy programs in order to assess the potential clinical application of XQ-1h.