Free Radical Injury in the Brain

Nitric oxide (NO), a free radical, has been shown to alter neuronal survival. Glutamate release during neuronal injury leads to both calcium influx into neurons and the production of NO. NO is toxic to the neuronal population under certain conditions, such as during glutamate release and during anoxia. As free radical, NO can react with superoxide to produce peroxynitrite, an agent that leads to cell lipid peroxidation. This process may account for the selective vulnerability of neurons in the hippocampus and cortex.

Experimental models have illustrated that ischemic generation of the free radical NO can be a "trigger" for the subsequent induction of neuronal injury in cortical neurons, hippocampal neurons, and mesencephalic neurons. Inhibition of NO production in cell culture systems during anoxia has been shown to be neuro-protective. During a global cerebral insult, production of NO is increased and nitric oxide synthase (NOS), the enzyme responsible for NO generation, is induced in hippocampal astrocytes. Blockade of NO formation by some NOS inhibitors can reduce infarction following middle cerebral artery occlusion and prevent cerebral endothelial cell disease such as atherosclerosis. In addition, inhibition of neuronal NO formation in transgenic animals can reduce infarction following middle cerebral artery occlusion. The cellular pathways generated by NO that result in neuronal injury are varied but include neuronal endonucleases, intra-cellular acidification, and cysteine proteases. As a result of its close link to the molecular pathways that lead to neuronal injury, NO functions not only as a potential therapeutic target but also as a valuable investigational agent. New clinical treatments, especially for organic brain disease, are now focusing on NO and the subsequent downstream pathways of neurodegeneration.

However, not all studies demonstrate a detrimental role for NO. Some experimental models have argued for the protective effects of NO-induced vasodilatation. Increased production of NO, in some circumstances, has been shown to decrease rather than increase cerebral stroke size in animals. Although these results have been attributed to improved cerebral perfusion to the ischemic penumbra, others have illustrated that improved cerebral perfusion alone to the ischemic zone is insufficient to sustain neuronal survival. It is unclear why certain environmental conditions may predispose NO to function as a neuroprotectant rather than a toxin. Several factors appear to contribute to these divergent observations and involve such parameters as the experimental model, external environmental conditions, duration of the insult, and age of the neuronal system.

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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