[Study on arousal effect of Orexin-A in rat in coma due to ischemic brain injury].

OBJECTIVE

To reproduce an ischemic brain injury coma model and explore the arousal effect of Orexin-A.

METHODS

An ischemic brain injury coma model was reproduced in rats by partial four-vessel occlusion (4-VO with a needle of 0.60 mm in diameter in the lumen to create stenosis of the internal carotid arteries). One hundred and twenty minutes after the onset of coma, Orexin-A or its antagonist (SB-334867) was given intraventricularly, and the time of coma and changes in electroencephalogram (ECG) were observed, and the unit discharge of neurons in the prefrontal cortex was recorded.

RESULTS

Partial occlusion of four internal carotid arteries, reducing the lumens to 0.60 mm, could prolong the time of coma to 6-8 hours with the rats still alive. The duration of coma showed a significant difference compared with that in rats who underwent 0.45 mm or 0.70 mm stenosis of the internal carotid arteries (F=344.43, P<0.01). Intraventricular Orexin-A in a dose of 4 nmol/10 microl could obviously decrease the duration of coma with a decrease in alpha wave and increase in unit discharge rate of neurons in coma rats (P<0.05 or P<0.01), but no significant change was observed when the dose was 2 nmol/10 microl.

CONCLUSION

(1)Creating stenosis of all four internal carotid arteries is suitable to reproduce ischemic brain injury with coma in rats. (2)Intracerebroventricular injection of Orexin-A (4 nmol) has a potent arousal effect on ischemic brain injury coma in rats.