THE PHOSPHOLIPASE A(2) INHIBITOR, QUINACRINE, REDUCES INFARCT SIZE INRATS AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION

The present study was conducted to evaluate the role of phospholipases in neuronal injury after transient focal ischemia. The phospholipase A(2) (PLA(2)) inhibitor, quinacrine (5 mg/kg) or saline (of equal volu me), was administered upon reperfusion to rats that underwent 2 h of m iddle cerebral artery occlusion (MCAO) via the intraluminal filament m ethod. Rats were graded for neurological deficits based on a scale of 0-4, where 0 indicates no visible neurological deficits and 3 indicate s most severe neurological deficits. After 2 h of focal ischemia, both groups of rats showed similar degrees of stroke, receiving median sco res of 4. However, after 24 h of reperfusion the quinacrine treated ra ts (n = 18) showed significantly lower deficit scores compared to the saline controls (n = 15). Median scores were 1 and 3 and mean ranks we re 12.28 and 23.14, respectively (P < 0.01, Mann-Whitney U-test). More over, this effect of quinacrine persisted for up to 7 days when the qu inacrine treated rats continued to receive a median score of 1, wherea s the saline treated rats received a median score of 2. The mean ranks were significantly lower in the quinacrine group (14.68) compared to the saline controls (21.54) (P < 0.05). After the last neurological te st was conducted, the rats were sacrificed and their brains embedded i n paraffin for histopathological analysis. Quinacrine treated rats sho wed significantly reduced infarct areas in the caudoputamen compared t o saline treated rats (P < 0.05, Student's t-test). When both cortical and striatal damage were summed, quinacrine treated animals also exhi bited a significantly lower degree of damage compared to saline contro ls (P < 0.05). This study supports the notion that PLA, plays an impor tant role in the development of neuronal injury following transient fo cal ischemia. (C) 1997 Elsevier Science B.V.