Reassessment of a new model of complete cerebral ischemia in rats. Method of induction of clinical death, pathophysiology and cerebrovascular pathology.
The present study was undertaken to ascertain the role of the microcirculation in the phenomenon of hypoperfusion following complete cerebral ischemia. The experiments were performed on rats under superficial ether anesthesia. Cerebral ischemia was induced by cardiac arrest for 3.5 or 10 min, with survival periods that lasted from 3 min to 7 days. A special metal hook-like device was inserted into the chest cavity at the third intercostal spaces for occluding the cardiac vessel bundle. The effect of this procedure was total cessation of systemic circulation, i.e., clinical death. In 52% of animals with 10-min clinical death, resuscitation (external heart massage and artificial ventilation) restored heart activity. When brain circulation was restored, respiratory activity, pain reaction, corneal reflex, bioelectric activity of the cortex, and normal activities of the rats returned. Scanning electron microscopy was applied to study the effect of ischemia on the vessel wall and endothelial cells (EC). Ischemia produced a remarkable increase in the numbers of microvilli and pit-like invaginations on the luminal EC surface. The luminal wall surface of many of the microvessels (MV) formed ridges. Frequently, microthrombi of varying sizes were observed. The most prominent changes were noted from 3 min to 6 h of recirculation, and they correlated with hypoperfusion after ischemia. Seven days later, these changes completely disappeared. The data presented here indicate that progressive hypoperfusion after ischemia occurs with significant alterations in the MV walls. These studies collectively suggest that the focal responses in select MVs may be associated with receptor molecule up-regulation of some, but not all, affected ECs. Our data provide further characterization of a new and unique chronic model of brain ischemia that can be applied to relevant clinical studies.
Pluta
R
R
NYS Institute for Basic Research in Developmental Disabilities, Department of Pathological Neurobiology, Staten Island 10314.
Lossinsky
A S
AS
Mossakowski
M J
MJ
Faso
L
L
Wisniewski
H M
HM
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003643:Death; D004195:Disease Models, Animal; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006323:Heart Arrest / Q000503:physiopathology; D006487:Hemostasis / Q000502:physiology; D008297:Male; D008833:Microcirculation; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011919:Rats, Inbred Strains