Thresholds of focal cerebral ischemia in awake monkeys

Abstract

An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

The CBF Threshold and Dynamics for Focal Cerebral Infarction in Spontaneously Hypertensive Rats

“…a Adapted from Morawetz et al (1978), Astrup et al (1981), Jones et al (1981), Bell et al (1985), andSymon (1985).…”

“…b Adapted from Symon et al (1974), Morawetz et al (1978), Jones et al (1981), Marcoux et al (1982), and Bell et al (1985). maintammg neuronal function, then the minimal blood flow that satisfies the energy needs of isch emic but viable brain tissue will critically depend on neuronal density.…”

“…The CBP threshold for histologic damage in focal cerebral ischemia is believed to lie between 10 and 17 ml 100 g -1 min -1, the exact level depending on the duration of the ischemic period (Morawetz et al, 1978;Astrup et al, 1981;Jones et al, 1981;Heiss, 1983;Heiss and Rosner, 1983;Symon, 1985). These threshold values are based on experiments performed predominantly in cats and primates but are usually viewed as applicable to other species.…”

Congenital destructive hemispheric lesions and epilepsy: clinical features and relevance of associated hippocampal atrophy

“…Moreover, most of the patients in this series with cystic lesions also have signs of gliosis around the lesion and at distance, which means that these insults have ocurred in a period when gliosis repair was already well developed. In addition, the nature and magnitude of an insult as well as its capacity to create a communication with the CSF system can be more relevant than the time of its occurence in determining the formation of a cystic or an atrophic lesion [29][30][31][32][33] .…”

Neuroprotective Treatment Strategies for Delayed Cerebral Ischemia after Subarachnoid Hemorrhage – Review of Literature and Future Prospects

“…Later in the course of the disease, the patients are threatened by delayed ischemic events which arise several days after aneurysm rupture. Concerning these delayed perfusion deficits; however, there is the unique opportunity to start therapeutic measures in advance, before cerebral blood flow (CBF) declines below ischemic thresholds [4]. Various forms of treatment have been tested and used to enhance CBF and protect the brain from ischemic deficits.…”