Gene transfer technique may be applicable to the treatment of serious types of stroke. Recently the concept of neurovascular protection is proposed as an important strategy for brain infarction. We have examined usefulness of gene transfer approach for neurovascular protection in brain ischemia. Using a focal brain ischemia model of spontaneously hypertensive rats, post-ischemic gene transfer of soluble Flt-1 markedly inhibited the ischemia-induced disruption of blood brain barrier permeability and attenuated ischemic damages. Gene transfer of dominant negative MCP-1 or interleukin-10 significantly inhibited infiltration of inflammatory cells and reduced infarct size. Using gene-deletion technique, we have found inflammatory interleukins mediated by infiltrated macrophages and γδT cells played pivotal roles in the evolution of brain infarction. Gene transfer of midkine, a novel growth factor, reduced apoptotic cell death and infarct volume with enhancement of neuronal precursor cell migration. Gene transfer technique appears to have a potential for neurovascular protection, and these molecular approaches may lead to the development of novel therapeutics for brain infarction.