A Reproducible New Model of Focal Ischemic Injury in the Marmoset Monkey: MRI and Behavioural Follow-Up.

Abstract

Ischemic stroke mostly affects the primary motor cortex and descending motor fibres, with consequent motor impairment. Pre-clinical models of stroke with reproducible and long-lasting sensorimotor deficits in higher-order animals are lacking. We describe a new method to induce focal brain damage targeting the motor cortex to study damage to the descending motor tracts in the non-human primate. Stereotaxic injection of malonate into the primary motor cortex produced a focal lesion in middle-aged marmosets (Callithrix jacchus). Assessment of sensorimotor function using a neurological scale and testing of forelimb dexterity and strength lasted a minimum of 12weeks. Lesion evolution was followed by magnetic resonance imaging (MRI) at 24h, 1 week, 4 and 12 weeks post-injury and before sacrifice for immunohistochemistry. Our model produced consistent lesions of the motor cortex, subcortical white matter and caudate nucleus. All animals displayed partial spontaneous recovery with long lasting motor deficits of force (54% loss) and dexterity (≈ 70% loss). Clearly visible T2 hypointensity in the white matter was observed with MRI and corresponded to areas of chronic gliosis in the internal capsule and lenticular fasciculus. We describe a straightforward procedure to reproducibly injure the motor cortex in the marmoset monkey, causing long-lasting motor deficits. The MRI signature reflects Wallerian degeneration and remote injury of corticospinal and corticopontine tracts, as well as subcortical motor loops. Our model may be suitable for the testing of therapies for post-stroke recovery, particularly in the chronic phase.