Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke

Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also predicts that areas of dense ischemia cannot be salvaged and that reperfusion of such areas is risky, because massive edema or even hemorrhage may develop following reperfusion. On this basis, it is argued that selection of stroke cases for thrombolysis or surgical revascularization must be based not only on computed tomographic (CT) scanning to exclude hemorrhagic stroke, but also on cerebral blood flow (CBF) tomography to exclude lacunar infarcts, early reperfusion, and dense ischemia. The methods available for routing CBF tomography in acute stroke cases are discussed, and it is concluded that single photon emission computed tomography (SPECT) using [99mTc]hexamethyl propyleneamine oxide (HM-PAO) or [99mTc]ethyl cysteinate dimer (ECD) should be explored for this use. In concluding, the glutamate receptor antagonist is mentioned. This compound is therapeutically active in some animal stroke models. In humans, it is probably used only in the acute phase, and in those in whom some degree of collateral flow is preserved. Therefore, even with this therapeutic approach, CBF tomography may be of value for patient selection.