Brain Advance Access published online on February 9, 2007
Brain, doi:10.1093/brain/awl393
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Inosine promotes recovery of skilled motor function in a model of focal brain injury
1Cambridge University Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK, 2Department of Pharmacology, Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, CA, USA, 3Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow and 4Neurosurgery Unit, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
Correspondence to:
James Fawcett, Cambridge Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Robinson Way, Cambridge, CB1 5RH, UK E-mail: jf108{at}cam.ac.uk
Recovery of function following traumatic brain injury (TBI) is partly through neuronal plasticity. However plasticity is limited in the adult CNS compared with young animals. In order to test whether treatments that enhance CNS plasticity might improve functional recovery after TBI, a new rat head injury model was developed, in which a computer-controlled impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex. Behavioural deficits were seen in several sensorimotor tasks, most of which recovered spontaneously by 21 days. However, skilled paw reaching behaviour, a task that requires corticospinal function, was only 
40% recovered by 28 days. In order to promote plasticity inosine was infused into the lateral ventricles for 28 days. This treatment produced an almost complete recovery of skilled paw reaching ability, associated with sprouting of the uninjured corticospinal axons across the midline into the territory of the lesioned pathway. In the cervical spinal cord the number of corticospinal axons originating from the uninjured cortex that innervated the contralateral cervical cord was five times that of controls, and in the red nucleus the number of contralaterally projecting axons was four times control values. Inosine treatment did not affect recovery in unskilled behavioural tasks, most of which recovered to normal levels by 28 days without treatment. Animals were placed in an enriched environment as an alternative method to promote plasticity. This resulted in more rapid recovery in several tasks including skilled paw function, but by 28 days normally housed animals had caught up to the same level of improvement.
Key Words: plasticity; head injury; corticospinal tract; spinal cord; behavioural assessment; axon sprouting
Abbreviations: CCI, controlled cortical impaction; TBI, traumatic brain injury
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Received October 22, 2006. Revised December 17, 2006. Second revision on December 21, 2006. Accepted December 22, 2006.
*These authors contributed equally to this work.
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