Akademik Veri Yönetim Sistemi
SENDROM, cilt.17, sa.5, ss.107-113, 2005 (Scopus)
Stroke and cardiac arrest, which are major causes of death and disability, affect millions of individuals around the world and are responsible for the leading health care costs of all diseases. The ischemia-induced neuronal death is an energy dependent process and is the result of activation of cascades of detrimental biochemical and histological events that include perturbion of calcium homeostasis leading to increased excitotoxicity, malfunction of endoplasmic reticulum and mitochondria, elevation of oxidative stress causing DNA damage, alteration in proapoptotic gene expression, and activation of the effector caspases and endonucleases leading to the final degradation of the genome. Ischemic preconditioning of the brain describes the neuroprotection induced by a short, conditioning ischemic episode to a subsequent severe ischemic episode. The tolerance of the brain to an ischemic injury depends not only on the duration and severity of insufficient blood flow but also on various pre- and post-ischemic factors that are able to influence the post ischemic outcome. Recent experimental studies focus on the preischemic factors, that can increase the ischemic tolerance, among which the suppression of metabolic rate, the increase of brain tissue energy reserves and the inhibition of membrane permeability of cations are of particular importance. During the induction phase, aspartate and adenosine receptors, and oxygen free radicals and conservation of energy metabolism are required. Protein kinases, transcription factors, and immediate early genes appear to transduce the signal into a tolerant response. The brain succumbs to ischemic injury as a result of loss of metabolic stores, excessive intracellular calcium accumulation, oxidative stress, and potentiation of the inflammatory response. Neurons can also die via necrotic or apoptotic mechanisms, depending on the nature and severity of the insult. While it has been widely held that ischemia is notable for cessation of protein synthesis, brain regions with marginal reduction in blood supply are especially capable of expressing a variety of genes, the functions of many of which are only beginning to be understood. Gene expression is also upregulated upon reperfusion and reoxygenation. Brain extracellular levels of glutamate, aspartate, GABA and glycine increase rapidly following the onset of ischemia, remain at an elevated level during the ischemia, and then decline following reperfusion. In the early stages neuronal responses to ischem ia are dependent on the modulation of ion channels. Reactive oxygen species generated during ische-mia-reperfusion contribute to the injury. Oxygen free-radicals serve as important signalling molecules that trigger inflammation and apoptosis. The use of appropriate animal models is essential to predict the value and effect of therapeutic approaches in human subjects. Animal models should be used to determine dosage and duration of therapy, which will vary with the pharmacokinetic properties of different agents. Finally, physiological monitoring for the metabolic condition such as cerebral blood flow, blood pressure and gazes, body temperature, glycemia, etc., should be performed to eliminate confounding variables and to observe adverse systemic effects. Therefore, it is very important to know the experimental process, survey of animals, neurologic scoring, histological methods which highly affect the explanation of the results. In this review, we discuss mechanisms of ischemic brain damage and reperfusion related to metabolic condition and histology.