Rat forebrain perfusion in vivo by 1 artery like the isolated kidney model: a robust recovery model permitting ischemia without anesthesia to compare multiple brain injury states.

BACKGROUND Rat brain perfusion models are critical to basic research, but they can be imprecise and/or not durable for extended outcome studies. OBJECTIVE To demonstrate a rat brain perfusion model that provides a simplified reliable brain perfusion circuit, reduces variables during experiment and recovery, and therefore permits more precise, reliable, and context-independent research data. METHODS Rat forebrain perfusion was reduced surgically to that by 1 internal carotid artery without injury to the animal. The next day, the fully awake rat was studied for brain ischemia painlessly yet in the absence of anesthesia or other interventions that might bias or alter the biochemistry of the event. This model was rigorously validated with isotope cerebral blood studies during ischemia and with histology studies at 72 hours after ischemia. The first application of this model was to compare ischemia injuries for global total, global penumbra, and global shock ischemia in a single experimental context. RESULTS This model is accurate, reliable, and remarkably durable. This model permits the severest brain ischemia by vessel occlusion ever demonstrated in a recovery model. It also confirms that, with conditions otherwise identical, penumbra ischemia is less injurious than total ischemia and that total ischemia is less injurious than shock ischemia. CONCLUSION Although meticulous in construction, this model creates ischemia more simply and more reliably than the Pulsinelli 4-vessel ischemia model that inspired it, with the inherent advantages of an isolated organ system, in which a known tissue volume is perfused at a predetermined volume and rate. This model permits robust long-term recovery.