Estrogens as neuroprotectants against ischemic stroke.
Estrogens have proven vasoprotective properties against atherosclerosis that depend on the direct effect on vascular smooth muscle and endothelium and on systemic actions that imply serum lipids, coagulation and fibrinolytic cascades, vasoactive proteins and antioxidant systems. They also have neuroprotective effects against cerebral ischemia that include antioxidant and anti-inflammatory effects, modulation of protein synthesis, inhibition of apoptosis and trophic effects and preservation of microvascular blood flow in the ischemic area. Estrogenic actions depend on activation of specific estrogen receptors that modulate gene expression and produce long-term effects on vascular endothelial and smooth muscle cells, neurons and glia, on interaction with plasma membrane sites that produce rapid non-genomic actions and also on receptor-independent mechanisms. This paper reviews what it is known about the mechanisms underlying the vaso- and neuroprotective effects of estrogens. Experimental and clinical evidences of such protective effects are also discussed. Therapeutical implications for stroke prevention and treatment derived from the available evidence are considered.
Alonso de Leciñana
María
M
Servicio de Neurología, Hospital Universitario Ramón y Cajal, Spain. mariaalonsoleci@telefonica.net
Egido
Jose Antonio
JA
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015201:Meta-Analysis as Topic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism
D004967:Estrogens; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen