Abstract 191: Optical Inhibition of Striatum Neuron Promotes Recovery After Ischemic Stroke

Introduction: Neurons of peri-infarct region in the cortex have effects on neurogenesis and remodeling after ischemic stroke. However the role of penumbral striatum neuron in neurogenesis and remodeling after ischemic stroke is unknown. In this study, we use optogenetic tools to specifically regulate the activity of striatum neuron and investigate its roles in neurogenesis and remodeling after ischemic stroke. Methods: Lentivirus carrying NpHR and YFP fusion protein under CaMKII promoter was injected into striatum of experimental mice. 7 days after injection, ferrule with fiber or optrode was implanted at the same position and MCAO surgery was performed 14 days after the injection. 4 days after MCAO, mice were stimulated with constant 594 nm laser for two 15-min sessions each day for 4 days. Electrophysiology test was used to confirm the validity of NpHR in vivo. Neurobehavioral tests were carried out at 3, 7 and 35 days after MCAO. Results: When stimulated with 594nm laser, the firing rate of striatum neuron was reduced in NpHR transduced mouse after MCAO. Immunohistochemistry showed that the number of BrdU and DCX double positive cells was significantly increased in the SVZ area. Nestin positive cells were increased both in SVZ and peri-infarct area. Western blotting showed that Netrin-1 expression was significantly up-regulated. BrdU and NeuN double positive cells was increased and brain atrophy volume was reduced in laser-stimulated mice compared with control mice (p<0.05). Neurobehavioral test showed that inhibition of striatum neuron promotes motor function after MCAO compared to the control (p<0.05). Conclusion: Laser induced activation of NpHR reduces the firing rate of penumbral striatum neuron using optogenetics tools. Inhibition of striatum neuron promotes proliferation and migration of neural progenietor cells and neurobehavioral function recovery. This effect is related to Netrin-1 secretion.