Non-neuronal responses to short-term occlusion of the middle cerebral artery

Stroke is the third cause of death and disability in the United States. The term "stroke," as used by epidemiologists, encompasses a group of three different neurologic disorders: ischemic strokes, intracerebral hemorrhage, and subarachnoid hemorrhage. The vast majority (75%) of strokes are of the ischemic type. An ischemic stroke is the clinical manifestation of the event initiated when a large intracranial artery becomes occluded by a thromboembolus.¹

In a prospective study that aimed to determine the causes of ischemic stroke among a cohort of nearly 2,000 patients, data from several hospitals that are integrated into the US National Stroke Data Bank revealed two significant facts. First, most ischemic strokes (about 41%) are the result of embolic/cryptogenic arterial occlusions, or events characterized by the sudden obstruction of blood flow through an otherwise normal intracranial artery. Second, the vessels most commonly involved by these occlusive events are the middle cerebral artery (MCA) or one of its main branches.²

It has been commonly accepted that the occlusion of an artery results in a parenchymal lesion called an infarction.³ In the case of an intracranial artery, we know from observations made on an experimental model of stroke that the moment the artery is occluded a corresponding neurologic deficit develops simultaneously with a regional decrease of the cerebral blood flow (CBF) and the appearance of an isoelectric EEG.⁴ We also know that, despite the prompt and marked loss of function, irreversible tissue injury will not be detectable until a few days later. Several issues, however, remain unresolved. First, how long must the artery remain occluded before an infarct (necrosis) appears in the ischemic brain? Second, what biological mechanisms that contribute to the eventual development of tissue necrosis are activated by arterial occlusion? Finally, are the brain lesions induced by arterial occlusions …