PARTIAL OR GLOBAL RAT-BRAIN ISCHEMIA - THE SCOT MODEL

A model for inducing partial (PBI) or global brain ischemia (GBI) in awake or anesthetized rats was obtained by ligating one subclavian and both carotid arteries (for PBI) or both subclavian-carotid arteries (for GBI). Rats were intubated and ventilated mechanically then subjected to a midline ventral incision from larynx to xiphoid process. The thorax was entered to expose the aortic arch and either one or both subclavians were ligated to eliminate each vertebral artery supply to brain. After chest closure the common carotid arteries were exposed and immediately ligated or else catheter snares were installed to induce ischemia at a later date. PBI was induced in 3 groups of rats for 7, 30 and 60 days while GBI was given for 5, 10, 30 and 75 minutes in 4 other groups. EEG became flat within 15 seconds after GBI and cortical cerebral blood flow (CBF) was reduced to "zero." EEG was unaffected after PBI but cortical CBF was reduced from a mean 118 ml/100 g tissue/min to 77 ml after 7 days. Morphological damage of CA1 hippocampal neurons after GBI or PBI was found reproducible and time dependent on ischemic duration. Acute cell damage rose from 5-95% in CA1 as GBI duration increased from 5-75 minutes. Similarly, chronic cell damage of CA1 increased as ischemic duration continued from 7-60 days in rats subjected to PBI. The advantages of the present model provide the option of inducing partial or global brain ischemia and of introducing postischemic reperfusion in awake or anesthetized preparations without the use of drugs, blood pressure manipulation or direct contact with brain tissue. Additionally, this model is simple and quick to prepare with EEG/CBF arrested within seconds after GBI, an event that promotes very consistent brain cell damage in a time-related fashion. The model should be useful in the study of acute or chronic cerebrovascular ischemia where neurochemical, morphological or physiological changes are anticipated.