Interrelation between inflammation, thrombosis, and neuroprotection in cerebral ischemia

Abstract

Stroke by mechanism of thrombotic cerebral ischemia is one of the leading causes of death and/or disability worldwide. Current research is under consensus that there are sex-based differences in both the prevalence and presentation of stroke and thrombosis. Here we discuss the interrelation between thrombosis and inflammation and call attention to points in the cerebral ischemic cascade where estrogen may be involved in neuroprotection. Cerebral ischemia triggers a series of events including inflammation, which is deeply interrelated with thrombosis; inflammation not only produces local thrombosis, but thrombosis can also amplify inflammation especially through the synergism of leukocyte and platelet activity. Research involving experimental animal models of cerebral ischemia has shown that sex hormones, especially estrogen, offer a degree of neuroprotection. Mechanisms of this neuroprotection may be linked to certain anti-inflammatory properties of estrogen, as well as estrogen's regulation of thrombosis through the lowering of coagulation factors, among others. It is also understood that sex hormones alter the function and morphology of platelets and fibrin networks, and changes in platelet and fibrin network morphology offer one of the earliest confirmations of inflammation. Sex hormone levels, inflammatory processes, and thrombotic mechanisms are profoundly interconnected in predicting the outcome of cerebral ischemia.