Hyperhomocysteinemia (hHCy) is a recognized comorbid risk factor of human brain stroke. We overview here the recent data on the homocysteine (Hcy) metabolism and on the genetic and metabolic causes of hHCy‐related neuropathologies. In context of our results which detected an increased oxidative stress in hyperhomocysteinemic rats, we discuss here the role of free radicals in this disorder. Brain ischemia‐reperfusion causes delayed neuronal death. Ischemic tolerance evoked by preconditioning (IPC) represents a phenomenon of central nervous system (CNS) adaptation to any subsequent ischemia. The paper describes changes in the mitogen‐activated protein kinases (MAPKs) protein pathways, and apoptotic markers were used to follow the degeneration process. Our studies provide evidence for the interplay and tight integration between extracellular signal‐regulated kinase (ERK) and p38 MAPKs signaling mechanisms in response to the hHCy and also in association with brain ischemia/IPC challenge. Recognition of the effects of risk factors in the ischemic tolerance would lead to improved therapeutics, especially the brain tissue.
Part of the book: Ischemic Stroke