Global brain ischemia: a reproducible monkey model.

Abstract

We developed a monkey model of 16 minutes global brain ischemia (GBI) resulting in reproducible, severe, permanent functional neurologic deficit with long term (7 days) postischemic (PI) survival made possible by standardized intensive care with 24 hour coverage by trained personnel. Quantitated neurologic deficit (ND) and brain histopathological examinations were developed. Fifteen minutes GBI resulted in rapid recovery within12--24 hours PI without residual neurologic sequelae. Twenty minutes GBI caused severe neurologic deficit and within 4 days PI, a delayed Cushing response eventually leading to cardiac arrest. Sixteen minutes GBI resulted in severe neurologic deficit (monkeys unable to sit, stand, walk, or feed themselves), but with long term survival. Brain histopathological analyses revealed a combination of cortical and brainstem lesions. Severest changes were observed in the occipital (calcarine) cortex with less severe damage in the frontal and temporal regions. Oculomotor nuclei and medial longitudinal fasciculus in the midbrain were regularly affected. With this model we can test the efficacy of promising therapies in terms of clinically relevant variables.