Enhancement of Braind -Serine Mediates Recovery of Cognitive Function after Traumatic Brain Injury
| Autor: | Anat Biegon, Barbara S. Slusher, Alcino J. Silva, Dana Atrakchi-Baranes, Kineret Rosenblatt, Efrat L. Kesner, Esther Shohami, Yael Friedman Levi, Sigal Liraz-Zaltsman |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Traumatic brain injury Receptors N-Methyl-D-Aspartate Serine Mice 03 medical and health sciences Cognition 0302 clinical medicine Brain Injuries Traumatic Animals Medicine business.industry Isoxazoles Recovery of Function medicine.disease Mice Inbred C57BL Neuroprotective Agents 030104 developmental biology Neurology (clinical) Cognition Disorders business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurotrauma. 35:1667-1680 |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2017.5561 |
| Popis: | Cognitive deficits, especially memory loss, are common and devastating neuropsychiatric sequelae of traumatic brain injury (TBI). The deficits may persist for years and may be accompanied by increased risk of developing early- onset dementia. Past attempts to reverse the neuropathological effects of brain injury with glutamate-N-methyl-d-aspartate (NMDA) antagonists failed to show any benefits or worsened the outcome, suggesting that activation, rather than blockage, of the NMDA receptor (NMDAR) may be useful in the subacute period after TBI and stroke. Activation of the NMDAR requires occupation of the glycine-modulatory site by co-agonists to achieve its synaptic functions. Glycine and d-serine are endogenous ligands/co-agonists of synaptic NMDARs in many areas of the mature brain. The aim of the present study was to evaluate the effect of 6-chlorobenzo(d)isoxazol-3-ol (CBIO), an inhibitor of D-amino acid oxidase (DAAO), which degrades d-serine, on cognitive outcome in a mouse model of TBI. Because treating TBI animals with CBIO elevates the endogenous levels of d-serine, we compared this novel treatment with treatment by exogenous d-serine alone and combined with CBIO. The results show that a single treatment (24 h post-injury) with CBIO in the mouse model of closed head injury significantly improves cognitive and motor function, and decreases lesion volume and the inflammatory response. Moreover, the compound proved to be neuroprotective, as the hippocampal volume and the number of neurons in hippocampal regions increased. Treatment with CBIO boosted the NR1 and phospho- NR1 subunits of the NMDAR and affected the CREB, phospho-CREB, and brain-derived neurotropic factor (BDNF) pathways. These findings render CBIO a promising, novel treatment for cognitive impairment following TBI. |
| Databáze: | OpenAIRE |
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