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Project

Motor cortex stimulation combined with immune modulation to achieve brain repair in vivo. (R-5262)

Cortical injuries resulting from traumatic brain injury (TBI) belong to the leading causes of disability and social burden amongst the young population and can cause severe post-damage disabilities, such as persistent impairments in motor functioning. Experiments conducted in stroke patients who suffered from hemiparesis showed that electrical stimulation of the motor cortex by flat epidural electrode pads caused increased motor recovery of the paretic arm. Also in animal experiments using rodent and nonhuman primate models of cortical damage, stimulation of the motor cortex led to functional recovery of the affected limb and tissue recovery in both cases, which was related to neuroplasticity processes. However, the underlying mechanisms explaining the clinical success of motor cortex stimulation (MCS) in functional regeneration are still to be revealed. In vitro studies, where neural stem cells (NSCs) were exposed to an electrical field, showed that those cells exhibited migration along the current gradient towards the cathode, a process called electrotaxis. In the current project, we hypothesize that electrotaxis is the main underlying mechanism, which explains the therapeutic effect of MCS. First, we will apply several electrical fields with different stimulation parameters to neural progenitor cells in vitro, to screen for the most efficient stimulation conditions inducing cell migration towards the cathode. Also the effect of those parameters concerning cell proliferation and -survival will be assessed. Findings from this experimental line will be translated to a future in vivo study where MCS combined with additional treatments will be applied in an animal model of TBI. Regeneration caused by a combined therapeutic approach will be assessed by behavioral tests measuring fine motor behavior in rodents, by measuring cortical functioning in the living animal and by characterizing the cell population at the lesion site post mortem. To verify that MCS is able to induce electrotaxis in vivo, endogenous NSCs are labeled and their potential migration path towards the cortical electrode can be visualized. Findings obtained in the current PhD project will help to evaluate the regenerative potential of MCS combined with more conservative therapies to restore motor functions. Furthermore, identification of the underlying mechanism of MCS will help to fine-tune this therapeutic approach for future purposes.
Date:1 Apr 2014 →  31 Mar 2016
Keywords:STEM CELLS, TRAUMATIC BRAIN INJURY
Disciplines:Morphological sciences