Ischemic preconditioning: a novel target for neuroprotective therapy.
Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons such as posttranslational modification of proteins or expression of new proteins via a signal transduction system to the nucleus. Secondly, a stress response and synthesis of stress proteins (heat shock proteins) may be activated. These mechanisms are mediated by chaperones. The objective of ischemic preconditioning research is to identify the underlying endogenous protective cellular receptors and signaling cascades, with the long-term goal of allowing therapeutic augmentation of the endogenous protective mechanisms in cerebral ischemia and possibly development of new neuroprotective strategies for ischemic stroke treatment.
Blanco
Miguel
M
Department of Neurology, Division of Vascular Neurology, Laboratory of Neurovascular Research, Hospital Clínico Universitario, University of Santiago de Compostela, Spain.
Lizasoain
Ignacio
I
Sobrino
Tomás
T
Vivancos
José
J
Castillo
José
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015221:Potassium Channels / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D017962:alpha-Linolenic Acid / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D015221:Potassium Channels; D017470:Receptors, Glutamate; D017962:alpha-Linolenic Acid; D000255:Adenosine Triphosphate; D003981:Diazoxide