The Interaction of Intramuscular Ketorolac (Toradol) and Concussion in a Rat Model
The purpose of this study was to examine the interaction of a single dose of Toradol and head impact in an in vivo rat model for sport-related concussion using a validated rat concussion model. Thirty-five Sprague–Dawley rats were placed into one of four groups: (1) Control, (2) Impact Only, (3) Toradol Only, (4) Impact and Toradol. Animals in the impact groups were subjected to a single head impact. Animals in the Toradol group received a single intramuscular injection of Toradol prior to impact. We examined magnetic resonance imaging, serum S100-B and cognitive function using a Morris Water Maze. In the control group, latency decreased significantly from day 0 (74.9 s) to 24 h (57.4 s) after anesthesia. There was no statistically significant difference between time zero and 24 h after impact in the Impact only or Impact and Toradol group. Our findings indicate that there were no differences between cognitive ability, MRI findings or S100B in rats that were administered a single dose of Toradol and subjected to a single impact and rats that were subjected to a single impact only. In both impact groups there were transient changes in cognitive ability as measured by the Morris Water Maze.
KeywordsHead impact Mild traumatic brain injury Sport related concussion
We thank Amanda Luba and Dr. Yimin Shen for their assistance with data collection. This study was funded internally. There are no financial conflicts of interest for any authors. This study was conducted at the Wayne State University Sports Injury Biomechanics Laboratory located at 818 W. Hancock, Detroit, MI.
- 3.Bouvier, D., T. Duret, M. Abbot, T. Stiernon, B. Pereira, A. Coste, J. Chazal, and V. Sapin. Utility of S100B serum level for the determination of concussion in male rugby players. Sports Med. 2016. doi: 10.1007/s40279-016-0579-9.
- 5.Buckley, E. M., B. F. Miller, J. M. Golinski, H. Sadeghian, L. M. McAllister, M. Vangel, C. Ayata, W. P. Meehan, 3rd, M. A. Franceschini, and M. J. Whalen. Decreased microvascular cerebral blood flow assessed by diffuse correlation spectroscopy after repetitive concussions in mice. J. Cereb. Blood Flow Metab. 35:1995–2000, 2015.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Connolly, E. S., Jr., C. J. Winfree, A. Rampersad, R. Sharma, W. J. Mack, J. Mocco, R. A. Solomon, G. Todd, D. O. Quest, Y. Stern, and E. J. Heyer. Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid endarterectomy. Neurosurgery 49:1076–1082; discussion 1082–1083, 2001.Google Scholar
- 9.Daneshvar, D. H., C. J. Nowinski, A. C. McKee, and R. C. Cantu. The epidemiology of sport-related concussion. Clin. Sports Med. 30:1–17, vii, 2011.Google Scholar
- 15.Huang, L., J. S. Coats, A. Mohd-Yusof, Y. Yin, S. Assaad, M. J. Muellner, J. E. Kamper, R. E. Hartman, M. Dulcich, V. M. Donovan, U. Oyoyo, and A. Obenaus. Tissue vulnerability is increased following repetitive mild traumatic brain injury in the rat. Brain Res. 1499:109–120, 2013.CrossRefPubMedGoogle Scholar
- 21.Matava, M., D. C. Brater, N. Gritter, R. Heyer, D. Rollins, T. Schlegel, R. Toto, and A. Yates. Recommendations of the national football league physician society task force on the use of toradol((r)) ketorolac in the national football league. Sports Health 4:377–383, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Pellman, E. J., J. W. Powell, D. C. Viano, I. R. Casson, A. M. Tucker, H. Feuer, M. Lovell, J. F. Waeckerle, and D. W. Robertson. Concussion in professional football: epidemiological features of game injuries and review of the literature—part 3. Neurosurgery 54:81–94; discussion 94–96, 2004.Google Scholar
- 29.Schulte, S., N. N. Rasmussen, J. W. McBeth, P. Q. Richards, E. Yochem, D. J. Petron, and F. G. Strathmann. Utilization of the clinical laboratory for the implementation of concussion biomarkers in collegiate football and the necessity of personalized and predictive athlete specific reference intervals. EPMA J. 7:1, 2015.CrossRefPubMedGoogle Scholar
- 30.Shaikh, H., M. Lechpammer, F. E. Jensen, S. K. Warfield, A. H. Hansen, B. Kosaras, M. Shevell, and P. Wintermark. Increased brain perfusion persists over the first month of life in term asphyxiated newborns treated with hypothermia: does it reflect activated angiogenesis? Transl. Stroke Res. 6:224–233, 2015.CrossRefPubMedGoogle Scholar
- 31.Shultz, S. R., F. Bao, V. Omana, C. Chiu, A. Brown, and D. P. Cain. Repeated mild lateral fluid percussion brain injury in the rat causes cumulative long-term behavioral impairments, neuroinflammation, and cortical loss in an animal model of repeated concussion. J. Neurotrauma 29:281–294, 2012.CrossRefPubMedGoogle Scholar
- 35.Viano, D. C., A. Hamberger, H. Bolouri, and A. Saljo. Concussion in professional football: animal model of brain injury—part 15. Neurosurgery 64:1162–1173; discussion 1173, 2009.Google Scholar