Effect of an Anion Transport Inhibitor, L-644,711, on Brain Injury and Edema After Temporary Middle Cerebral Artery Occlusion in Rats

The affect of L-644,711, an anion transport inhibitor, on ischemic brain injury and edema was investigated. Spontaneously hypertensive rats were given one of the following doses of intrathecal L-644,711 during 180 min of middle cerebral artery occlusion and 120 min of reperfusion: control, vehicle only; dose I, 100 microg/kg: dose II, 200 microg/kg; dose III, 250 mug/kg; or dose IV, 320 microg/kg. Immediately after the 5-h period of ischemia and reperfusion, the brains were analyzed for brain injury with 2,3,5-triphenyltetrazolium chloride, and for edema by microgravimetry (specific gravity). There were no between-group differences in specific gravity (brain water content). Brain injury (% of the hemisphere ipsilateral to middle cerebral artery occlusion) was less (p <0.05) in rats that received the 250 (35 +/- 5%, mean +/- SD) or 320 microg/kg (36 +/- 6%) doses of L-644,711 vs. the control group (47 +/- 5%). L-644,711 has been hypothesized to affect brain injury by improving the neuronal acid-base state, inhibiting astroglial swelling, decreasing neutrophil aggregation, or reducing glutamate release. The microgravimetric data do not support astroglial swelling as a primary mechanism of decreased brain injury.