Grant: Project Grant

Inflammation after injuries of the brain or spinal cord is generally viewed as negative as it potentially adds to tissue damage. We have however shown that inflammation seems to also play an important role in rewiring the nervous system after injuries and thus contributing to recovery, especially when it is combined with rehabilitative training. Thus, inflammation is a double edged sword that has to be applied carefully when used as a treatment. In this proposal we will explore whether and how the beneficial aspects of inflammation can be harnessed without causing detrimental effects. For this we will first investigate at what time points after injury is beneficial for training induced recovery in rats and how reducing inflammation can potentially affect recovery. Furthermore we will explore a promising cellular messaging pathway (i.e., histamine release) that translates inflammation to rewiring of the nervous system. We will start the experiments using cells and then a rat model of spinal cord injury to test whether inhibiting this pathway (for example by giving antihistamine drugs) reduces recovery and the effects of training and activating the pathway promotes recovery. Lastly, we will investigate a second mechanism how histamine can affect motor recovery as it potentially directly influences neuronal function.