Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Abstract

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis

“…This compensatory behavior, indicative of altered motor function and spatial perception, is a well-documented response to stroke-induced impairments. 18 Recent research indicates that compensatory use of the unaffected limb post-MCAO activates the contralateral motor cortex, facilitating neural reorganization and functional recovery, as observed in enhanced motor cortex activity and functional connectivity. 30 Cognitively, there was a noticeable decline in working memory, as evidenced in the delayed-response task at 1-month post-MCAO (Figure 4B).…”

“…16 Chronic white matter injury manifests as increased MD and decreased FA have been consistently observed in stroke patients 17 and NHP stroke model. 18 T h i s c o n t e n t i s Proteomics has become an indispensable tool in stroke research, identifying biomarkers and therapeutic targets while illuminating proteomic alterations across different stroke phases. 19 Extensive studies in rodent and NHP models have uncovered over 7000 differentially expressed proteins in ischemic core and penumbra regions, implicated in critical processes like cell death, survival, and recovery.…”

Determination of the Unilaterally Damaged Region May Depend on the Asymmetry of Carotid Blood Flow Velocity in Hemiparkinsonian Monkey: A Pilot Study

“…Further studies are warranted to elucidate the changes in cerebral blood fow before and after infusion of MPTP. Additionally, the investigation of hemiparkinsonian behavioral signs using a hand dexterity task for hand function or a gait-sensing walkway system for locomotion should be considered for comparison of MPTP-induced damage to basal ganglia subregions [32,33].…”

“…All MRI examinations were conducted using a Philips 3T Achieva scanner (Philips Medical System, Best, Netherlands) with a 32-channel head coil. Monkeys were comfortably restricted in a supine position in a custom-made bed holder during MRI scans [ 17 , 32 , 33 ]. Inhaled CO 2 , O 2 saturation, pulse, respiration rate, and body temperature were continuously monitored.…”

“…Care. Te interventional radiology method employed in this study was performed as reported in our previous studies [17,[30][31][32][33]. All monkeys were anesthetized with ketamine (5 mg/kg, I. M, Yuhan, Seoul, South Korea) and maintained with isofurane (2%, Hana Pharmacy, Hwaseong, South Korea).…”