Inosine enhances recovery of grasp following cortical injury to the primary motor cortex of the rhesus monkey

Article type: Research Article

Authors: Moore, Tara L.^{a; b; *} | Pessina, Monica A.^a | Finklestein, Seth P.^d | Killiany, Ronald J.^a | Bowley, Bethany^a | Benowitz, Larry^e | Rosene, Douglas L.^{a; c}

Affiliations: [a] Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA | [b] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [c] Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA | [d] Stemetix, Inc, Needham, MA, USA | [e] Department of Neurosurgery and F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Corresponding author: Tara L. Moore, Tel.: +617 638 4054; Fax: +617 6384922; E-mail: [email protected].

Abstract: Background: Inosine, a naturally occurring purine nucleoside, has been shown to stimulate axonal growth in cell culture and promote corticospinal tract axons to sprout collateral branches after stroke, spinal cord injury and TBI in rodent models. Objective: To explore the effects of inosine on the recovery of motor function following cortical injury in the rhesus monkey. Methods: After being trained on a test of fine motor function of the hand, monkeys received a lesion limited to the area of the hand representation in primary motor cortex. Beginning 24 hours after this injury and continuing daily thereafter, monkeys received orally administered inosine (500 mg) or placebo. Retesting of motor function began on the 14th day after injury and continued for 12 weeks. Results: During the first 14 days after surgery, there was evidence of significant recovery within the inosine-treated group on measures of fine motor function of the hand, measures of hand strength and digit flexion. While there was no effect of treatment on the time to retrieve a reward, the treated monkeys returned to asymptotic levels of grasp performance significantly faster than the untreated monkeys. Additionally, the treated monkeys evidenced a greater degree of recovery in terms of maturity of grasp pattern. Conclusion: These findings demonstrate that inosine can enhance recovery of function following cortical injury in monkeys.

Keywords: Inosine, cortical injury, rhesus monkey, recovery, motor function

DOI: 10.3233/RNN-160661

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 5, pp. 827-848, 2016