The phospholipase A2 inhibitor, quinacrine, reduces infarct size in rats 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 A2 (PLA2) inhibitor, quinacrine (5 mg/kg) or saline (of equal volume), was administered upon reperfusion to rats that underwent 2 h of middle cerebral artery occlusion (MCAO) via the intraluminal filament method. Rats were graded for neurological deficits based on a scale of 0-4, where 0 indicates no visible neurological deficits and 4 indicates most severe neurological deficits. After 2 h of focal ischemia, both groups of rats showed similar degrees of stroke, receiving median scores of 4. However, after 24 h of reperfusion the quinacrine treated rats (n = 18) showed significantly lower deficit scores compared to the saline controls (n = 15). Median scores were 1 and 3 and mean ranks were 12.28 and 23.14, respectively (P < 0.01, Mann-Whitney U-test). Moreover, this effect of quinacrine persisted for up to 7 days when the quinacrine treated rats continued to receive a median score of 1, whereas 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 test was conducted, the rats were sacrificed and their brains embedded in paraffin for histopathological analysis. Quinacrine treated rats showed significantly reduced infarct areas in the caudoputamen compared to saline treated rats (P < 0.05, Student's t-test). When both cortical and striatal damage were summed, quinacrine treated animals also exhibited a significantly lower degree of damage compared to saline controls (P < 0.05). This study supports the notion that PLA2 plays an important role in the development of neuronal injury following transient focal ischemia.
Estevez
A Y
AY
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Phillis
J W
JW
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000209:etiology* / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine