Stroke Longitudinal Volumetric Measures Correlate with the Behavioral Score in Non-Human Primates

Stroke is the second leading cause of death worldwide. Brain imaging data from experimental rodent stroke models suggest that size and location of the ischemic lesion relate to behavioral outcome. However, such a relationship between these two variables has not been established in Non-Human Primate (NHP) models. Thus, we aimed to evaluate whether size, location, and severity of stroke following controlled Middle Cerebral Artery Occlusion (MCAO) in NHP model correlated to neurological outcome. Forty cynomolgus macaques underwent MCAO, after four mortalities, thirty-six subjects were followed up during the longitudinal study. Structural T2 scans were obtained by magnetic resonance imaging (MRI) prior to, 48 h, and 30 days post-MCAO. Neurological function was assessed with the Non-human Primate Stroke Scale (NHPSS). T2 whole lesion volume was calculated per subject. At chronic stages, remaining brain volume was computed, and the affected hemisphere parceled into 50 regions of interest (ROIs). Whole and parceled volumetric measures were analyzed in relation to the NHPSS score. The longitudinal lesion volume evaluation showed a positive correlation with the NHPSS score, whereas the remaining brain volume negatively correlated with the NHPSS. Following ROI parcellation, NHPSS outcome correlated with frontal, temporal, occipital, and middle white matter, as well as the internal capsule, and the superior temporal and middle temporal gyri, and the caudate nucleus. These results represent an important step in stroke translational research by demonstrating close similarities between the NHP stroke model and the clinical characteristics following a human stroke and illustrating significant areas that could represent targets for novel neuroprotective strategies.