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

Abstract

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 2h of middle cerebral artery occlusion (MCAO), followed by 24h 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, 3h after induction of ischemia. Subsequently, 24h after MCAO brain edema, infarct volume, neurological deficits and cerebral blood flow were evaluated. Administrations of XQ-1h at the doses of 31.2mg/kg at 0.5, 1, and 2h 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 (31.2mg/kg) treatment, 0.5, 1, and 2h after reperfusion produced significant improvement in neurological score compared to vehicle-treated group (P<0.01). Administrations of XQ-1h at the doses of 31.2mg/kg and 15.6 mg/kg at 0.5, 1, and 2h 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 2h. 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.

• Authors: Jing Sun, Yunman Li, Weirong Fang, Lishun Mao
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 666 Issue 1-3 Pg. 105-10 (Sep 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21645512 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Ginkgolides
• Lactones
• XQ-1H compound
• Malondialdehyde
• Superoxide Dismutase
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Brain Edema (complications, drug therapy)
• Cerebrovascular Circulation (drug effects)
• Drug Administration Schedule
• Ginkgolides (administration & dosage, therapeutic use)
• Infarction, Middle Cerebral Artery (physiopathology)
• Lactones (administration & dosage, therapeutic use)
• Male
• Malondialdehyde (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (complications, drug therapy, metabolism, physiopathology)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Superoxide Dismutase (metabolism)