Microvascular disturbances and edema formation after repetitive ischemia of gerbil brain

Abstract

Three transient episodes of 5 min ischemia spaced at 1-h intervals were produced in Mongolian gerbils by bilateral carotid artery occlusion with an implanted vascular occlusion device. The interval of 1 h was chosen to allow for the development of post-ischemic hypoperfusion between the ischemic episodes. Three minutes and 1 h after each ischemic episode, and 6 and 24 h after the third occlusion, Evan's blue (EB) was injected intravenously to trace circulating blood, and the number of perfused capillaries was determined in various brain regions by fluorescence microscopy. Brain edema was evaluated by measuring specific gravity in tissue samples taken from adjacent areas. Repetitive ischemia caused progressively increasing brain edema and a progressive reduction of the number of perfused capillaries. Immediately after each ischemic episode, transient recruitment of capillaries occurred, thus excluding no-reflow as a main pathogenetic factor of microcirculatory disturbances. The pattern of microcirculation 6 and 24 h after the last occlusion revealed a redistribution of circulating blood, characterized by a reduction in the number of EB-filled capillaries associated with a noticeable dilatation of the larger vascular channels. Our studies suggest a close interrelationship between post-ischemic microcirculatory hypoperfusion and the development of brain edema, the degree and extent of which progresses with the repetition of ischemic episodes when they are carried out during the periods of hypoperfusion.

Role of angiogenesis in patients with cerebral ischemic stroke.

“…Even a short period (5 minutes) of experimental ischemia causes disturbances in capillary blood flow, ie, hypoperfusion in one region and hyperperfusion in another. 12 The repeated occurrence of ischemia causes a progressive increase in edema of endothelial cells and brain tissue, infiltration of white blood cells into nerve tissue, and damage to neurons. Fewer perfused capillaries remain even though total blood flow and total vascular volume return to control levels.…”

Characterization of Hypothermia-induced Cellular Stress Response in Mouse Tissues

“…5A). Although the brain initiates the stress response following as little as 5 min of ischemia (20,21), it is not likely that this is the explanation for the high levels of HSF1 DNA binding even in the cage control as we removed the brains in less than 45 s following sacrifice. Interestingly, this HSE binding activity is due to both HSF1…”

Deficient induction of human hsp70 heat shock gene transcription in Y79 retinoblastoma cells despite activation of heat shock factor 1.

“…Expression of hsp70 in neuronal cells is induced by ischemia, kainic acid-induced epilepsy, and trauma (15,17,18); yet the classical stimulus of heat shock does not uniformly elicit a response from neuronal cells either in vivo (19) or in vitro (12,13). Of particular interest have been studies on primary cultures of cortical neurons and cerebellar granule cells in which hsp70 expression is notably deficient upon heat shock (12,13).…”