Mechanisms of lesion and exercise induced regeneration after brain stem stroke

• Applicant: Professor Dr. Jens Minnerup
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215825344

Ischemic strokes occur in different locations within the brain, such as the cerebrum, the cerebellum, and the brain stem. Brain stem strokes feature a high symptom severity and account for about 15% of all ischemic strokes. So far, no animal models for brain stem strokes were available and therefore pathophysiological mechanisms and new treatments for this disease could not be experimentally investigated. The previous funding was used to characterize a newly developed photothrombotic brain stem stroke model in rats. Mechanisms of injury, the secondary neuronal damage, and behavioral deficits were investigated. The present proposal aims to determine brain remodeling processes after brain stem ischemia. There processes are well defined for supratentorial stroke including both, lesion-induced and exercise-induced neuronal plasticity. The ability to increase neuronal plasticity by exercise points out that regenerative processes can be modified and therefore represent a potential therapeutic target. Relevant mechanisms of regeneration such as neurogenesis and axonal sprouting depend on the location of the infarct. After supratentorial stroke the increased neurogenesis is pronounced in the ipsilateral subventricular zone (SVZ), whereas axonal sprouting of the contralateral pyramid tract can be therapeutically enhanced. We therefore hypothesized that mechanisms known from infarcts of the cerebrum cannot simply be adopted to brain stem strokes. Indeed, our preliminary data show that ischemia of the brain stem, in contrast to ischemia of the cerebrum, does not induce neurogenesis in known neurogenic niches, i.e. the SVZ or the hippocampus. However, a number of neuronal progenitor cells, likely of spinal origin, were identified in the peri-ischemic tissue within the brain stem. The finding of spinal cord derived neuronal progenitor cells migrating to a brain stem lesion was not described before.The proposed project aims to identify the underlying mechanisms of the lesion- and exercise-induced neuronal plasticity after brain stem stroke. Our results will be of scientific relevance but also of clinical importance since a better understanding of remodeling processes can improve the treatment of brain stem stroke.

• DFG Programme: Research Grants