Â鶹´«Ã½Ó³»­

Â鶹´«Ã½Ó³»­

Explore the latest content from across our publications
Join The Â鶹´«Ã½Ó³»­

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Regional Variation in Sulfonylurea Receptor-1 Regulated Channel Expression after Repetitive Mild Traumatic Brain Injury in Mice: An Exploratory Study
Neuro Trauma, Critical Care, and Sports Neurology
P11 - Poster Session 11 (8:00 AM-9:00 AM)
5-010

To investigate brain region-specific expression of Sulfonylurea Receptor-1 (SUR-1) and its regulated channels (TRPM4, KIR6.2) after repetitive-mild traumatic brain injury (rmTBI).

SUR-1 upregulation is emerging as a key mediator of cerebral edema and neuronal death in many central nervous system pathologies. Targeted inhibition of  SUR1-TRPM4 has shown promising results in clinical trials of stroke and TBI. This pathway remains unexplored in rmTBI, where despite its therapeutic potential in a spectrum of at-risk patients including child-athletes, football players, and soldiers, the role of brain edema and/or other consequences of SUR-1 activation remains controversial.

Anesthetized 63-day old C57/BL6 mice (n=12) underwent a repeated weight-drop model of rmTBI (53g from 42 inches for 2 days, followed by a larger impact of 80g from 60 inches on day-3). Shams (n=3/time-point) underwent anesthesia only.  Mice were sacrificed 6h (n=3/group) and 24h (n=3/group) after final injury. The left hippocampus, thalamus, cortex, and cerebellum were isolated for quantitative-rtPCR of Abcc8 (Sur-1), Kcnj11, and Trpm4 using Gapdh as reference.

No expression differences were noted at 6h. 24h Abcc8(Sur-1) expression increased 1.79-fold (p=0.006) in injured cortex vs sham, but decreased (0.35 fold-change, p=0.015) in thalamus.  There was a trend for increased cortical Trpm4 expression (1.93 fold, NS) 24h following injury. 24h thalamic Kcnj11 expression was decreased (0.68 fold-change, p=0.006) but cortical Kcnj11 was not different (0.59 fold-change, NS) vs sham. 
This exploratory study represents a novel report of Abcc8(Sur1) upregulation 24h following rmTBI, identifying a potential treatable target. Surprisingly, SUR-1 and its regulated ion-channels undergo robust region-specific expression changes in rmTBI. Increased cortical Abcc8(Sur-1) may represent increased SUR1-TRPM4 expression/facilitate co-localization of the depolarizing non-specific monovalent cation channel. Decreased thalamic Abcc8(Sur-1) expression was accompanied by decreased Kcnj11 (Kir6.2). Regional Sur1 differences with potentially variable electrochemical consequences may have important pathophysiological and therapeutic implications for rmTBI. 
Authors/Disclosures
Benjamin Zusman, MD (MGB Neurology)
PRESENTER 		Mr. Zusman has received research support from University of Pittsburgh .
Patrick M. Kochanek, MD, MCCM (University of Pittsburgh) Patrick M. Kochanek, MD, MCCM has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Washington. Patrick M. Kochanek, MD, MCCM has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Johns Hopkins Health System. Patrick M. Kochanek, MD, MCCM has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for de Boisblanc Law Firm. The institution of Patrick M. Kochanek, MD, MCCM has received research support from Chuck Noll Foundation. The institution of Patrick M. Kochanek, MD, MCCM has received research support from NIH. Patrick M. Kochanek, MD, MCCM has received publishing royalties from a publication relating to health care.
No disclosure on file
No disclosure on file
Ruchira M. Jha, MD (Barrow Neurological Institute) Dr. Jha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. An immediate family member of Dr. Jha has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Legal fees. The institution of Dr. Jha has received research support from NIH/NINDS, Chuck Noll Foundation, University of Pittsburgh, Barrow Neurological Foundation.