TY - JOUR
T1 - Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats
AU - Yu, Yu Wen
AU - Hsieh, Tsung-hsun
AU - Chen, Kai-Yun
AU - Wu, John Chung Che
AU - Hoffer, Barry J.
AU - Greig, Nigel H
AU - Li, Yazhou
AU - Lai, Jing Huei
AU - Chang, Cheng-Fu
AU - Lin, Jia-Wei
AU - Chen, Yu Hsin
AU - Yang, Liang-Yo
AU - Chiang, Yung-Hsiao
PY - 2016/5/9
Y1 - 2016/5/9
N2 - Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.
AB - Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-84996899109&origin=resultslist&sort=plf-f&src=s&st1=Glucose-Dependent+Insulinotropic+Polypeptide+Ameliorates&st2=&sid=09b859af2c12cc35ed4856137b03ea7a&sot=b&sdt=b&sl=71&s=TITLE-ABS-KEY%28Glucose-Dependent+Insulinotropic+Polypeptide+Ameliorates%29&relpos=1&citeCnt=4&searchTerm=
UR - https://www.scopus.com/results/citedbyresults.uri?sort=plf-f&cite=2-s2.0-84996899109&src=s&imp=t&sid=3824137025cc72ad07291819c8c5cfc4&sot=cite&sdt=a&sl=0&origin=recordpage&editSaveSearch=&txGid=d4f2e652473a33b6138635f21231154f
U2 - 10.1089/neu.2015.4229
DO - 10.1089/neu.2015.4229
M3 - Article
C2 - 26972789
SN - 0897-7151
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
ER -
