Thrombin inhibition attenuates neurodegeneration and cerebral edema formation following transient forebrain ischemia

The disturbance of microcirculation following cerebral ischemia leads to an enlargement of cerebral infarct volume. Endogenous thrombin may play a rol e in this disturbance of microcirculation following cerebral ischemia. Ther efore, the inhibition of thrombin may improve neurodegeneration and the acc umulation of cerebral edema following cerebral ischemia in gerbils. The eff ects of thrombin inhibitor (argatroban) on cerebral ischemia were investiga ted in comparison with thromboxane A2 synthase inhibitor (ozagrel) and cycl ooxygenase inhibitor (aspirin) following bilateral common carotid artery oc clusion and reperfusion (CCA:O/R) in male Mongolian gerbils. This study con sisted of three experiments: ( 1) morbidity and survival ratio (n =40 for e ach), (2) histopathology (n = 12 for each), and (3) mean arterial brood pre ssure, local cerebral blood flow (CBF), and cerebral specific gravity (n=8 for each). Argatroban treatment improved survival ratio and stroke index, a nd decreased ischemically injured cell numbers in cortex and hippocampus an d cerebral edema in cortex compared with aspirin and saline, in concert wit h the fast recovery of local CBF without reactive hyperemia following bilat eral CCA:O/R. Ozagrel treatment also improved those factors compared with s aline, in concert with the fast recovery of local CBF with reactive hyperem ia. Aspirin treatment improved survival ratio and stroke index, and decreas ed ischemically injured cell numbers in cortex. Thrombin inhibition with ar gatroban decreases neurodegeneration and cerebral edema following bilateral CCA:O/R in gerbils. (C) 2001 Elsevier Science B.V. All rights reserved.