TY - JOUR
T1 - Novel pharmaceutical treatments for minimal traumatic brain injury and evaluation of animal models and methodologies supporting their development
AU - Deselms, Hanna
AU - Maggio, Nicola
AU - Rubovitch, Vardit
AU - Chapman, Joab
AU - Schreiber, Shaul
AU - Tweedie, David
AU - Kim, Dong Seok
AU - Greig, Nigel H.
AU - Pick, Chaim G.
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/10/15
Y1 - 2016/10/15
N2 - 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.
AB - 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.
KW - Animal models of TBI
KW - Exendin-4
KW - N-Acetyl-L-cycteine
KW - Salubrinal
KW - Thrombin
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=84959057070&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2016.02.002
DO - 10.1016/j.jneumeth.2016.02.002
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AN - SCOPUS:84959057070
SN - 0165-0270
VL - 272
SP - 69
EP - 76
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
ER -