There is considerable evidence suggesting that under normal circumstances there is a coupling between the metabolic demands of the central nervous system and the cerebral blood flow (CBF) supplying substrates necessary to meet these demands. There is also evidence that this normal relationship between CBF and metabolic activity is altered in a variety of pathological situations such as stroke and hypoglycemia. Pathological situations such as hypertension and ischemia can also result in impairment of blood-brain barrier (BBB) function. Previous studies of concussive head injury have demonstrated that many aspects of cerebrovascular reactivity such as pressure and chemical autoregulation are altered after trauma. Concussive head injury has also been demonstrated to cause changes in BBB permeability. We postulate that abnormal alterations in the relationship between CBF and metabolic activity as well as changes in BBB permeability may be major contributing factors to pathophysiological changes seen after head trauma. We propose to study regional CBF (radioactive microsphere technique), local cerebral utilization of glucose (2-deoxyglucose technique) and regional, quantitative BBB function (aminoisobutyric acid technique) simultaneously within the same tissue samples in normal and head injured animals. In addition, we propose to carry out neurochemical assays of high energy phosphate and lactate levels in a separate series of identically treated animals. Following regional analyses of the feline brain using these techniques, brain areas shown to be preferentially affected by brain injury will be subjected to morphological analysis. Thus, the proposed studies will provide important information concerning regional changes in the relationship between CBF and metabolism and BBB permeability after concussive brain injury. Moreover, this protocol will allow us to relate these changes to trauma-induced ultrastructural pathologies as well as to derangements in energy production system.
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