Date of Completion


Embargo Period



EAE, MS, Neuroinflammation, Spinal cord, Choroid plexus

Major Advisor

Dr.Joel S. Pachter

Associate Advisor

Dr. Robert E. Cone

Associate Advisor

Dr. James Watras

Associate Advisor

Dr Stephen Crocker

Field of Study

Biomedical Science


Doctor of Philosophy

Open Access

Open Access


Dysfunction of the blood brain barrier (BBB), the specialized complex of cells situated at the central nervous system (CNS) microvasculature has been associated with numerous neuroinflammatory disorders like multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). BBB known to restrict passage of soluble and cellular elements between the blood and CNS is breached. The mechanism by which auto-reactive T cells cross the normally “impermeable” BBB, invade the initially naive CNS, and cause neuroinflammation, remains unclear. Recent studies suggest an initial route by which these cells first gain entry from circulating blood through the choroid plexus (CP). The permeable fenestrated capillaries of CP allow these sentinal T cells into the cerebrospinal fluid (CSF) across the surrounding tight junction expressing choroidal epithelium also known as the blood-CSF-barrier (BCSFB). Once into the CSF, these cells travel to the subarachnoid space (SAS) that surrounds the CNS parenchyma. Here, T cells are known to encounter their cognate antigen and set off a cytokine storm that propagates inflammation. The effects are first observed within the SAS in the meningeal vessels followed by activation of parenchymal inflammation. However, several critical questions in this scenario remain. First, how do these T cells cross the epithelium of the CP to enter the CSF? Does this involve changes in the tight junctional integrity between adjacent epithelial cells to allow leukocyte diapedesis? Second, once they enter the CSF, do these cells select a segment within the SAS to ignite the inflammatory sequence? Given the ascending inflammation within spinal cord segments in developing EAE (caudal to rostral), regional blood vessels in meninges and parenchyma might display unique vulnerabilities depending upon the segment of the spinal column in which they reside. Third, what links the inflammatory signals in the SAS to neuroinflammation in the parenchyma? Results obtained from this work show evidence towards the hypothesis that the ascending course of EAE is due to initial penetration of sentinal T cells through a structurally compromised CP choroidal epithelium, followed by a spinal segment-dependent relay of inflammatory signals between meningeal and parenchymal vessels.