K. Ibraheem1, A. J. Sandweiss2, T. M. Largent-Milnes2, A. Azim1, N. Kulvatunyou1, L. Gries1, T. W. Vanderah2, P. Rhee3, T. O’Keeffe1, B. Joseph1 3Grady Memorial Hospital,Trauma And Surgical Critical Care/Department Of Surgery,Atlanta, GA, USA 1The University Of Arizona,Trauma,critical Care, Burn And Emergency Surgery/Department Of Surgery/School Of Medicine,Tucson, AZ, USA 2The University Of Arizona,Department Of Pharmacology,Tucson, AZ, USA
Introduction: Remote ischemic conditioning (RIC) has been shown to have protective effects in in a number of different clinical settings including coronary bypass surgery and kidney transplantations. There is recent evidence to suggest its beneficial role in preventing secondary brain insults in traumatic brain injury. The aim of our study was to examine the role of RIC in a mouse model of traumatic brain injury.
Methods: 100 male C57BL mice were subjected to a cortical controlled impact injury. Two hours after TBI, animals were allocated to RIC (n = 10) or Sham (n = 10). RIC was performed for 6 cycles of ischemia and reperfusion by clamping the femoral artery. Circulating levels of S100-B, neuron specific enolase (NSE) and Glial fibrillary acidic protein (GFAP) were serially measured as markers of damage to neurons and astrocytes at 2-, 6-, 24-, 48- and 120-hours post-intervention (RIC or Sham). Similarly, another 24 animals were subjected to a cortical controlled impact injury. Two hours after TBI, animals were allocated to RIC (n = 12) or Sham (n = 12) then assessed at 2-, 24-, 48-, 72- and 96-hours post-intervention (RIC or Sham) for cognitive performance using novel object recognition. The motor coordination was assessed by rotarod test at 24-, 48-, 72-, 96- and 120-hours post-intervention (RIC or Sham).
Results: There was no significant difference in systemic neuronal markers between RIC and Sham animals at 2-, 6-, and 24- hours. Serum GFAP trended down while serum NSE and S100-B trended up in both RIC and Sham animals. RIC animals had significantly higher recognition index than Sham at 24-, 48 and 72-hours post-intervention (Figure). Latency to fall was higher in RIC animals compared to Sham animals at all time points and statistically significant at 120-hours post-intervention. The RIC group demonstrated significantly improved cognitive function and motor coordination compared to the Sham group.
Conclusion: The application of remote ischemic conditioning 2 hours post-injury results in quicker recovery of cognitive functions and improved balance and motor coordination in a mouse model of traumatic brain injury despite no significant changes in systemic biomarkers of brain injury.
