Gateway Reflexes Are Stimulated by Neural Activations and Promote the Pathogenesis of Multiple Sclerosis Models

Abstract The central nervous system (CNS) is tightly regulated by the blood–brain barrier. This regulation is compromised in patients with neuroinflammatory diseases such as multiple sclerosis (MS), which allows immune cells to infiltrate the CNS. We identified a gateway, dorsal vessels of the fifth lumbar (L5) cord, for this infiltration using MS mouse models. The gateway is regulated by local neural activation. Sensory neurons activated by gravity induce local norepinephrine production via sympathetic nerve activations, which increases the expression of chemokines to attract autoreactive CD4 + T cells at L5 dorsal vessels. Neural activation caused by other stimulations, such as electric pulses and pain sensation, also results in gateways. This chapter focuses on these gateway reflexes, which are critical for immune reactions in the CNS.