title: Inosine improves functional recovery after experimental traumatic brain injury.
abstract: Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits. Inosine, a naturally occurring purine nucleoside, has been shown to promote axon collateral growth in the corticospinal tract (CST) following stroke and focal TBI. In the present study, we investigated the effects of inosine on motor and cognitive deficits, CST sprouting, and expression of synaptic proteins in an experimental model of closed head injury (CHI). Treatment with inosine (100 mg/kg i.p. at 1, 24 and 48 h following CHI) improved outcome after TBI, significantly decreasing the neurological severity score (NSS, p<0.04 vs. saline), an aggregate measure of performance on several tasks. It improved non-spatial cognitive performance (object recognition, p<0.016 vs. saline) but had little effect on sensorimotor coordination (rotarod) and spatial cognitive functions (Y-maze). Inosine did not affect CST sprouting in the lumbar spinal cord but did restore levels of the growth-associated protein GAP-43 in the hippocampus, though not in the cerebral cortex. Our results suggest that inosine may improve functional outcome after TBI.
authors: Department of Pharmacology, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel; Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel.
authors: Shlomit
authors: S
authors: Dachir
authors: Department of Pharmacology, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors: Dalia
authors: D
authors: Shabashov
authors: Department of Pharmacology, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors: Victoria
authors: V
authors: Trembovler
authors: Department of Pharmacology, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors: Alexander G
authors: AG
authors: Alexandrovich
authors: Department of Neurosurgery, Children׳s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors: Larry I
authors: LI
authors: Benowitz
authors: Department of Pharmacology, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. Electronic address: esty.shohami@mail.huji.ac.il.
authors: Esther
authors: E
authors: Shohami
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007288:Inosine / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D011712:Pyramidal Tracts / Q000473:pathology; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D020127:Recovery of Function; D045442:Rotarod Performance Test; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D016708:Synaptophysin; C569015:Syp protein, mouse; D007288:Inosine
keywords: Cortical spinal tract (CST); GAP-43; Novel object recognition test (NORT); Synaptophysin; Y-maze