Restorative therapies

Experimental studies of the recent past have shown that neurological recovery can be stimulated by neuronal plasticity-promoting therapies post-stroke in rodents. Using video-based behavioral tests, histochemical and molecular biological techniques, this group examines, how neuronal plasticity after stroke can be promoted by growth factors (e.g., erythropoietin), cell-based therapeutics (e.g., neural stem and precursor cells, stem cell-derived exosomes) and pharmacological compounds (i.e., drugs). An important focus of our works is the characterization of axonal connectivity by means of anterograde and retrograde tract tracing methods (Figure 1). Research results of the group already led to the translation of a pharmacological compound, the GABAA-α5 antagonist S44819, into a large worldwide clinical phase II multicenter study, RESTORE Brain, which is currently performed in Europe, North and South America, Asia and Australia in stroke patients.

Our research projects at a glance:

Effects of growth factors, cell-based therapeutics and pharmacological compounds on neurological recovery, neuronal plasticity and brain remodeling after focal cerebral ischemia
Analysis of axonal connectivity by anterograde and retrograde tract tracers
Analysis of dendritic arborizations and synaptic densities using Golgi-Cox stainings
Effects of age, vascular risk factors (e.g., dyslipidemia) and dietary influences (lipid-rich nutrition, malnutrition) on neurological recovery and neuronal plasticity
Effects of disturbed blood-brain barrier integrity (following deactivation of ATP-binding cassette transporters) on neurological recovery and neuronal plasticity

Publications

Bacigaluppi M, Pluchino S, Peruzzotti-Jametti L, Kilic E, Kilic U, Salani G, Brambilla E, West MJ, Comi G, Martino G, Hermann DM. Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms. Brain. 2009; 132:2239-51.

Hermann DM, Chopp M. Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol. 2012; 11:369-80.

Reitmeir R, Kilic E, Kilic U, Bacigaluppi M, ElAli A, Salani G, Pluchino S, Gassmann M, Hermann DM. Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. Brain. 2011; 134:84-99.

Reitmeir R, Kilic E, Reinboth BS, Guo Z, ElAli A, Zechariah A, Kilic U, Hermann DM. Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain. Acta Neuropathol. 2012; 123:273-84.

Wang YC, Sanchez-Mendoza EH, Doeppner TR, Hermann DM. Post-acute delivery of memantine promotes post-ischemic neurological recovery, peri-infarct tissue remodeling, and contralesional brain plasticity. J Cereb Blood Flow Metab. 2016; May 11.