Therapeutic Strategies for Traumatic Brain Injury with Novelly Desinged Drugs( I )

In this project, the research collaboration between USA and Taiwanese principle investigators (PIs) is based on long term mutual interest in neuroprotection against traumatic brain injuries (TBI). Both USA PI (Dr. Nigel H. Greig, NIH) and Taiwanese PI (Dr. Jia-Yi Wang, TMU) are well-trained neuroscientists and work collaboratively right from data mining to experimental designing. The USA PI (Dr. Greig) has developed several therapeutic strategies and novel experimental drugs including anti-apoptotic p53 inactivators, anti-inflammatory agents targeting TNF-α synthesis inhibition, and GLP-1 receptor agonists, and will continue optimizing the translation of drugs from the bench to the bedside. The Taiwanese PI (Dr. Wang) has successfully established animal models of TBI with various degree of severity. She has also set up a well-equipped neurobehavior lab to monitor multiple neurological functions of small animals to evaluate the therapeutic effects of the novel designed drugs on TBI, including water maze (memory functions), rotarod (motor coordination), beam walking (motor coordination), tactile adhesiveremoval (somatosensory functions). The central hypothesis of this project is that intervening in common biochemical cascades leading to cell death that are shared between degenerative diseases and TBI will help to optimize the translation of drugs from the bench to the bedside. Designed compounds will be provided by Co-PI (Dr. Greig in USA) of this project. Since these compounds have been proved effective in preventing neuronal cell loss in models of degenerative diseases (stroke, Parkinson disease and Alzheimer disease) in culture and animals, we will examine the therapeutic effects and time windows of these compounds in TBI models with various degree of severity. Designed compounds will be provided by Dr. Greig (Co-PI in USA). Using the established animal models, the Taiwanese PI (Dr. Wang) will systematically examine the time course and severity of TBI and the therapeutic benefit of these compounds through evaluating neurological functions by multiple behavioral tests (rotarod, tactile adhesive removal, mNSS and beam walk) and measurement of contusion volume by cresyl violet staining of brain sections. In addition, Dr. Wang will also screen and identify a series of biosignature (miRNAs and/ or proteins) in plasma or CSF from these TBI animals at 4 different phases (acute, subacute, chronic, and prognostic) and correlate with the severity and progression of TBI to determine the best combinations or miRNA and proteins as biosignatures. The effects of these designed compounds on the potential biosignatures will also be examined to validate the biosignatues. Several of these experimental drugs have already moved to the clinic and, if effective in TBI, can be rapidly translated to clinical efficacy trials for TBI treatment. The approval of the joint project will allow us to strength newly born scientific collaboration between the two institutions (in NIH in USA and TMU in Taiwan) and participants will be directly involved in tasks assigned to the other country counterparts, with relevance in scientific formation in specific methodologies. This joint action will also be important in the preparation of future collaborations between the two institutions and larger multi-national research project.