Cerebral phospholipid content and Na+,K+-ATPase activity during ischemia and postischemic reperfusion in the mongolian gerbil.

Using bilateral carotid artery occlusion in adult gerbils we examined the effects of ischemia and ischemia/reperfusion on cerebral phospholipid content and Na+,K+-ATPase (EC 3.6.1.3) activity. In contrast to the large changes in phospholipid content and membrane-bound enzyme activity that have been observed in liver and heart tissues, we observed relatively small changes in the cerebral content of total phospholipid, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE) following ischemic intervals of up to 240 min. Following 15 min of ischemia the cerebral content of sphingomyelin (SM) was decreased to less than 50% of control values but returned to near-normal levels with longer ischemic periods. Significant decreases in the cerebral content of phosphatidylinositol (PI) and phosphatidic acid (PA) were observed following shorter intervals of ischemia (15-45 min). Na+,K+-ATPase activity of cerebral homogenates prepared from the brains of gerbils subjected to 30-240 min of ischemia was decreased but significantly different from control activity only after 30 min of ischemia (-29%, p less than or equal to 0.05). With the exception of PS, reperfusion for 60 min following 60 min of ischemia resulted in marked increases in cerebral phospholipid content with PC, SM, PI, and PA levels exceeding and PE levels equal to preischemic values. Longer periods of reperfusion (180 min) resulted in decreases in cerebral phospholipid content toward (PC, SM, PI, and PA) or below (PE) preischemic levels. In contrast, the cerebral content of PS significantly decreased during reperfusion (-51% at 60 min, p less than or equal to 0.05) and remained below preischemic values even after 180 min of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

A gerbil model of cerebral ischemia suitable for drug evaluation.

Cerebral ischemia was produced in the Mongolian gerbil by bilateral occlusion of the carotid arteries. Although the cerebral ischemia so produced was not total, a mortality rate of 100% was obtained if the occlusion was maintained for 60 min in gerbils weighing 45--55 gm. Few deaths were observed after 50 min of bilateral carotid arterial occlusion. Test drugs were administered, after the removal of the arterial clips, to groups of gerbils to determine the mortality rate associated with each drug. Isoproterenol 50 mg/kg, amphetamine 5.0 mg/kg, and methylprednisolone 35 mg/kg improved survival after cerebral ischemia. Atropine 1 mg/kg, thiosemicarbazide 4 mg/kg, aminooxyacetic acid 100 mg/kg, theophylline 100 mg/kg, and phenytoin 50 mg/kg were associated with a reduced survival after cerebral ischemia. The known tendency of the gerbil to exhibit spontaneous seizures and the frequency and severity of the observed post-ischemic seizures suggest that the lethality of prolonged cerebral ischemia may be, in part, related to seizures triggered by the cerebral ischemia.