Abstract WMP42: Neuro and Gliogenesis in a Nonhuman Primate Model of Ischemic Stroke with Impaired Dexterous Movements

Abstract

Ischemic stroke is the leading cause of upper extremity motor impairments. Well-characterized experimental stroke models for upper extremity motor impairment remain underdeveloped. Cortical representation of dexterous movements in nonhuman primates (NHP) is functionally and topographically similar to that in humans. We recently reported the characterization of an NHP model of focal ischemia reperfusion with a defined syndrome, impaired arm function and finger dexterity. In this study, we investigated the cellular changes in the neural stem cell compartment and glial cell populations in this NHP model. NHPs were subjected to transient cerebral ischemia by temporarily occluding the M3 segment of the left side middle cerebral artery (MCA). Motor and cognitive functions following the stroke were evaluated using the object retrieval task with barrier-detour. Postmortem analysis included magnetic resonance imaging (MRI) and immunohistopathology to map the infarct and characterize the neurogenic and gliogenic changes. The MCA occlusion produced significant loss of fine motor function characterized by impaired dexterity. Immunocytochemical analysis revealed significant increase of Sox2+ neural stem cells in the subventricular zone, and of GFAP+ astrocytes (P<0.0001) and Iba-1+ microglia (P<0.0001) in the infarct region. In addition, there was a 42% increase in doublecortin positive cells (P<0.0001) compared to non-ischemic hemisphere. This study describes the cellular composition of the endogenous changes in the neural stem cell compartment and in the stroke region. These data may help reveal the cellular identity mediating neural plasticity and the cellular mechanisms mediating behavioral deficits and post-stroke recovery.