Stroke Neurodegenerative conditions

FIGURE 4—16. Calcium may also rush into cells too quickly if its ion channels are opened too much, as is postulated to occur as a result of certain toxins, by stroke, or by neurodegenerative conditions (see Fig. 4—17). 

A limited form of excitotoxicity may be useful as a pruning mechanism for normal maintenance of the dendritic tree (see Fig. 1—23), getting rid of cerebral dead wood like a good gardener however, excitotoxicity to an excess is hypothesized to cause various forms of neurodegeneration, ranging from slow, relentless neurodegenerative conditions such as schizophrenia and Alzheimer s disease to sudden, catastrophic neuronal death such as stroke (Fig. 10—26). 

Among the most important and challenging neurological disorders are neurodegenerative conditions (such as Parkinson s disease, Alzheimer s disease, and amyotrophic lateral sclerosis), stroke, brain tumors, epilepsy, migraine, and multiple sclerosis. 

Bcl-2 family proteins are attractive targets for drug development. Conceivably, inhibitors of the pro-apoptotic members would block apoptosis prior to cytochrome c release and caspase activation and may have therapeutic value for conditions that appear to involve excess apoptosis (e.g., neurodegenerative disorders and ischemia associated with stroke and heart attack). Activators of the pro-apoptotic members or inhibitors of the anti-apoptotic members would have value in treating disorders that appear to progress as a result of too little apoptosis (e.g., cancer and autoimmunity). 

This condition is referred to as ischemia-reperfusion injury. Several studies in animal models of ischemia-reperfusion injury have shown that the principal cause of cellular death is necrosis (11-13). However, other smdies have shown that cellular death consisted of a necrotic core surrounded by a peri-necrotic area that displayed properties consistent with apoptosis (11,14-18). Therefore, it is likely that cellular death resulting from ischemia-reperfusion injury can consist of a mixture of apoptosis and necrosis, depending on the extent and duration of the ischemia prior to reperfusion. Other disease conditions where evidence demonstrating both apoptosis and necrosis occur includes diabetic cardiomyopathy, sepsis, stroke, and the neurodegenerative disorders Alzheimer s disease and Parkinson s disease. The development of a noninvasive imaging technique capable of measuring apoptosis and necrosis independently could provide valuable information on the balance between apoptosis and necrosis, and if there is a temporal shift in the balance of these mechanisms of cellular death, in a wide variety of pathological conditions. 

---