Peter Bergold, MD

Combination drug therapy for the treatment of traumatic brain injury (TBI)

At present, TBI cannot be treated with drugs. Recent research in my laboratory has focused on developing therapeutics to treat TBI. The pathophysiology of TBI is complex, we hypothesized that drug combinations may be more effective than monotherapy. We screened pairs Food and Drug Administration-approved drugs that had off-label efficacy against TBI. Drugs pairs were screened for synergistic improvement in a hierarchy of behavioral tasks (Abdel Baki, et al., 2009). The combination of minocycline and N-acetylcysteine synergistically improved both task acquisition and retention after TBI. (Abdel Baki, et al., 2010). Strikingly, neither minocycline nor N-acetylcysteine had any effect on task retention or memory. The drug combination, however, potently prevented memory deficits. One focus of the laboratory is to understand how these two drugs synergize to prevent memory deficits. We have also recently characterized a widespread demyelination in an animal model of TBI. The drug combination of minocycline and N-acetylcysteine restored myelin by inducing remyelination. Remyelination may be an important new target for drugs to treat TBi.

• Abdel Baki, S.G.Schwab, B., Haber, M., Fenton, A. A. and P.J. Bergold (2010) Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury, PLOSone. 5: e12490.
• Oselkin, M., Tian, D., and Bergold, P.J. (2010) Low-dose cardiotonic steroids increase sodium potassium ATPase activity that protects hippocampal slice cultures from experimental ischemia. Neuroscience Lett. 473:67-71.
• Yao Y, Bergold PJ, Penington NJ. (2010) Acute Ca(2+)-dependent desensitization of 5-HT(1A) receptors is mediated by activation of protein kinase A (PKA) in rat serotonergic neurons. Neuroscience 169:87-97.
• Benardete, E.A., Bergold, P.J. (2009) Genomic analysis of ischemic preconditioning in adult rat hippocampal slice cultures. Brain Res. 1292:107-22
• Abdel Baki, S.G., Kao, H.-Y., Kelemen, E., Fenton, A.A., Bergold. P.J., (2009) A hierarchy of neurobehavioral tasks discriminates between mild and moderate brain injury in rats Brain Res. 1280:98-106.
• Bergold, P.J., Pinkhasova, V., Syed, M., Kao, H.-Y., Zhao, N., Coplan, J.D., Diana Dow-Edwards, D., Fenton, A.A. (2009) Production of panic-like symptoms by lactate is associated with increased neural firing and oxidation of brain redox in the rat hippocampus. Neurosci. Lett. 453:219-24.