Hanna Deselms1, Nicola Maggio2, Vardit Rubovitch1, Joab Chapman3, Shaul Schreiber4, David Tweedie5, Dong Seok Kim5, Nigel H Greig5, Chaim G Pick6. 1. Department of Anatomy and Anthropology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 2. Department of Neurology, The J. Sagol Neuroscience Center, The Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel; Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel; Department of Neurology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Department of Neurology, The J. Sagol Neuroscience Center, The Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel; Department of Neurology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Department of Psychiatry, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5. Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. 6. Department of Anatomy and Anthropology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: pickc@post.tau.ac.il.
Abstract
BACKGROUND: The need for effective pharmaceuticals within animal models of traumatic brain injury (TBI) continues to be paramount, as TBI remains the major cause of brain damage for children and young adults. While preventative measures may act to reduce the incidence of initial blunt trauma, well-tolerated drugs are needed to target the neurologically damaging internal cascade of molecular mechanisms that follow. Such processes, known collectively as the secondary injury phase, include inflammation, excitotoxicity, and apoptosis among other changes still subject to research. In this article positive treatment findings to mitigate this secondary injury in rodent TBI models will be overviewed, and include recent studies on Exendin-4, N-Acetyl-l-cycteine, Salubrinal and Thrombin. CONCLUSIONS: These studies provide representative examples of methodologies that can be combined with widely available in vivo rodent models to evaluate therapeutic approaches of translational relevance, as well as drug targets and biochemical cascades that may slow or accelerate the degenerative processes induced by TBI. They employ well-characterized tests such as the novel object recognition task for assessing cognitive deficits. The application of such methodologies provides both decision points and a gateway for implementation of further translational studies to establish the feasibility of clinical efficacy of potential therapeutic interventions.
BACKGROUND: The need for effective pharmaceuticals within animal models of traumatic brain injury (TBI) continues to be paramount, as TBI remains the major cause of brain damage for children and young adults. While preventative measures may act to reduce the incidence of initial blunt trauma, well-tolerated drugs are needed to target the neurologically damaging internal cascade of molecular mechanisms that follow. Such processes, known collectively as the secondary injury phase, include inflammation, excitotoxicity, and apoptosis among other changes still subject to research. In this article positive treatment findings to mitigate this secondary injury in rodent TBI models will be overviewed, and include recent studies on Exendin-4, N-Acetyl-l-cycteine, Salubrinal and Thrombin. CONCLUSIONS: These studies provide representative examples of methodologies that can be combined with widely available in vivo rodent models to evaluate therapeutic approaches of translational relevance, as well as drug targets and biochemical cascades that may slow or accelerate the degenerative processes induced by TBI. They employ well-characterized tests such as the novel object recognition task for assessing cognitive deficits. The application of such methodologies provides both decision points and a gateway for implementation of further translational studies to establish the feasibility of clinical efficacy of potential therapeutic interventions.
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