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Abstract
Cell death may be accomplished by at least two distinct mechanisms: necrosis and apoptosis.Apoptosis is programmed cell death,while necrosis is in general a form of cell death that rapidly occurs in response to severe insults such as anoxia and cell trauma.
Although necrosis and apoptosis are morphologically distinct, it is becoming more evident that necrosis and apoptosis are likely part of a conti¬nuum of cell death and similar mechanisms may be operative in both processes.Considering various mechanisms of pro¬grammed cell death, either during neural development or neurodegeneration, finding the most suitable and effective protective strategy needs evaluation of risk-to-benefit ratio.Defining molecular mechanisms is, therefore, the necessary step preceding the adaptation of new protective and then, possibly, therapeutic strategies.
Apoptosis is a common phenomenon induced either by specific insults mediated through so-called “death receptors” (external pathway) or by non-specific insults leading to re¬duction of mitochondrial potential (internal pathway). At the molecular level, apoptosis is regulated by the activation of the caspase cascade. The mitochondrial pathway is different from that of the death receptor (Fas) pathway, yet they are connected.
A widely accepted hypothesis suggests that neuronal cell death is mainly a consequence of competition for limited target-derived neurotrophic factors. Neurotrophins acting to promote neuronal sur¬vival through different mechanisms. Thus shortages of neurotrophic factors promotes apoptosis.
Various pharmacological compounds have been evaluated for their possible potential neuroprotective value through out interfering with various mechanisms of cell death.
Discovering the precise mechanisms of action of such compounds carries out great promise for better understanding of the disease process and discovering possible crucial steps in the pathogenesis of such diseases that could be targeted for neuroprotection.
Promising results were found in studies & research work on cell culture and animal models, yet applying that to human clinical trials didn’t show the same success.However various clinical trials are still going on aiming to avoid possible mistakes in previous trilas.
Possible neuroprotective mechanisms of various pharmacological compounds were mentioned in this review including; Neuroprotection against neuronal apoptosis, glutamate action modulation,ion channels modulation, inflamatory process modulation,antioxidants,estrogen,opiods,cannabenoids,erythr-opoietin and others.
In addition to that non pharmacological neuroprotection was also reviewed including; hypothermia,preconditioning and hibernation.