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Stroke is the third most common cause of death in most industrialized countries with an estimated global mortality of 4.7 million per year. Each year, about 700 000 people suffer new or recurrent stroke. It is the major cause of serious, long-term disability, with more than 1 100 000 American adults reporting functional limitations resulting from stroke. Also, recent evidence suggests that the presence of small strokes or of local chronic ischemia may be much more common in aging populations than previously thought.
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Stroke is more common in men than women, although at older ages, the incidence is higher in women than in men. Unlike traumatic brain injury (TBI), there is one treatment that is somewhat successful in a subpopulation of stroke victims. The thrombolytic, tissue plasminogen activator (tPA) has been proved to be effective in treating stroke when given within 3 hours after onset of neurologic symptoms. Although stroke and traumatic brain primarily affects different age groups, both result in a significant number of individuals with long-term deficits.
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PATHOPHYSIOLOGY OF FOCAL ISCHEMIA
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Normal cerebral blood flow (CBF) in men is typically in the range of 45–50 mL/min/100 g between a mean arterial pressure (MAP) of 60 and 130 mm Hg. When CBF falls below 20–30 mL/min/100 g, marked disturbances in brain metabolism begin to occur, such as water and electrolyte shifts and regional areas of the cerebral cortex experience failed perfusion. At blood flow rates below 10 mL/min/100 g, sudden depolarization of the neurons occurs with rapid loss of intracellular potassium to the extracellular space.
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Ischemic and traumatic brain injury results from the interaction of complex pathophysiologic processes that are activated by ischemic or traumatic events. In both injury settings, areas of risk are present that may be salvaged by specific treatment strategies. Although each of these pathophysiologic mechanisms is a target for therapeutic interventions, the complex interaction of these pathomechanisms may make it difficult for targeted pharmacological agents to protect the brain long-term and improve behavioral outcome. Also tissue responses to different injury severities and types (ie, ischemic vs traumatic) may differ and, therefore, complicate treatment strategies not tailored to individual cases.
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Current knowledge regarding the pathophysiology of cerebral ischemia and brain trauma indicates that similar mechanisms contribute to loss of cellular integrity and tissue destruction. Mechanisms of cell damage include excitotoxicity, oxidative stress, free radical production, apoptosis, and inflammation. Genetic and gender factors have also been shown to be important mediators of pathomechanisms present in both injury settings. However, the fact that these injuries arise from different types of primary insults leads to diverse cellular vulnerability patterns as well as a spectrum of injury processes.
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Blunt head trauma produces shear forces that result in primary membrane damage to neuronal cell bodies, white matter structures, and vascular beds as well as secondary injury mechanisms. Severe cerebral ischemic insults lead ...