Neuroimaging and histopathological evaluation of delayed neurological damage produced by artificial occlusion of the middle cerebral artery in Cynomolgus monkeys: establishment of a monkey model for delayed cerebral ischemia.

ABSTRACT

A monkey model (Cynomolgus) was established to evaluate the delayed neurological damage evident at areas distant from ischemic cerebral foci. In addition to proton magnetic resonance spectroscopy (MRS) monitoring in life, histological examinations of specimens of the brain was conducted on lesions produced 6h and 1, 2, 4 and 8 weeks after unilateral (left) permanent middle cerebral artery occlusion (pMCO) on five monkeys. In addition to the typical images evident at primary ischemic foci around the middle cerebral artery, MRS revealed and enhanced, clearer region, due to edema extending into the reticular and compact area of the left substantia nigra one week after pMCO, inducing right hemiparesis caused by focal cerebral ischemia. Similar histological lesions were also induced in the left thalamus 4 weeks after pMCO. Thereafter, a variety of histological findings including astrocytic activation, reduced number of nerve cells and gliosis were found in the above described areas far apart from the original ischemic cerebral foci. Our monkey model should be suitable for studies elucidating the pathological process in cerebral ischemia as well as for investigating therapeutic strategies involving ischemic stroke in humans.