Brain-Specific Migration and Protective Roles in Brain Damage of Microglia

Abstract

The ability to manipulate the expression of genes within the mammalian brain provide unique opportunities to study and to potentially treat neurological disorders. The introduction of certain genes specifically in brain has been done with viral vectors or cells carrying DNA. However, these methods require surgery. Recently, we found that primary isolated microglia specifically entered the brain from blood flow when the cells were injected intra-arterially.¹ Microglia, macrophage-like cells in the brain, are multi-functional cells; they play important roles in the development, differentiation and maintenance of neural cells via their phagocytic activity and production of enzymes, cytokines and trophic factors.² Since intra-arterially-injected microglia were labeled with fluorescent dye microparticles by their phagocytic activity, this system could apply to a brain-specific delivery for medicines, or other bioactive materials, such as proteins or genes.³ To apply this brain-specific bio-targeting system for treatment of neurological disorders, vehicle microglia should migrate to the region of insult and not augment the insult. Therefore, we investigated migration of systemically injected microglia into the ischemic brain.