Synaptic Characteristics In Peri-infarct Cortex And A Role Of Recombinant Osteopontin In Axonal Sprouting After Stroke

Ischemic stroke is a main cause of adult disability,significantly impacting Chinese people and national economic development.The aim of this study is to establish a murine focal photothrombotic stroke model,and to analyze synapses,blood vessel density and astrocytes in the peri-infarct cortex after stroke at different time points.We also test the expression levels of synaptophysin and tubulin in this area to determine the optimal time period for its ability of spontaneous neural repair after stroke.Previously,we have identified significantly increased osteopontin(OPN)message in the sprouting neurons.We now focus on mechanisms of the mouse recombinant OPN(r OPN)in promoting axonal sprouting and possible functional recovery after stroke.We observe notably higher numbers or density for synapses,blood vessels and astrocytes in the peri-infarct,all of which reach the highest level particularly in the primary sensory cortex 7 days after stroke.While the expression of synaptophysin is significantly upregulated,tubulin is statistically decreased at 7 days after stroke,showing that cortical neurons may have a spontaneous but limited effect to neural repair post-stroke.We then give r OPN protein into the infarct core at 7 days post-stroke for 24 hours and find that r OPN promotes the axonal sprouting,increases blood vessel density,and elevates number of astrocytes in the cortical tissue adjacent to the infarct.r OPN is also found to reduce infarct volume,indicating that r OPN could significantly improve functional recovery following ischemic stroke.Further,Western blot data demonstrate that r OPN is mainly regulated at least through integrin.To sum up,we have characterized the occurrence of spontaneous axonal sprouting in the mouse primary somatosensory cortex after stroke.Axonal sprouting appears accompanied with the regeneration of blood vessels and the proliferation of astrocytes,which in turn provides support for the establishment of new synapses.The upregulation of synaptophysin and formation of microtubules may enhance synaptic plasticity.Promoting axonal sprouting in the peri-infarct cortex with local r OPN administration may improve behaviors after stroke and provide us an alternative strategy to stroke therapeutics.