Research: Cell gateway to the brain

Epub: Schmitt et al. Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the forebrain and midbrain. J Neuroinflammation. 2012 Aug 7;9(1):187.

BACKGROUND: The cerebrospinal fluid (CSF) has been considered as a preferential pathway of circulation for immune cells during neuroimmune surveillance. In order to evaluate the involvement of CSF-filled spaces in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we performed a time course analysis of immune cell association with the CSF-containing ventricles, velae, and cisterns in two active models of this disease.


METHODS: Guinea-pig spinal cord homogenate-induced EAE in rat and myelin oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte distribution and phenotypes were investigated by immunohistochemistry in serial sections of brain areas of interest, as well as in CSF withdrawn from rat. Immune cells associated with the choroid plexuses were quantified.

RESULTS: Freund's adjuvant-induced peripheral inflammation in the absence of brain antigen led to a subtle but definite increase in the number of myeloid cells in the extraventricular CSF spaces. In both rats and mice, EAE was characterized by a sustained and initial infiltration of lymphocytes and monocytes within forebrain/midbrain fluid-filled compartments such as the velum interpositum and ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated periventricular and pericisternal parenchymal areas, along perivascular spaces or following a downward CSF-to-tissue gradient. Cells, quantified in CSF sampled from rats, included lymphocytes and neutrophils. The distinctive pattern of cell distribution suggests that both the choroid plexus and the vessels lying in the velae and cisterns are gates for early leukocyte entry in the central nervous system. B-cell infiltration observed in the mouse model was restricted to CSF-filled extraventricular compartments.

CONCLUSION: These results identified distinctive velae and cisterns of the forebrain and midbrain as preferential sites of immune cell homing following peripheral and early central inflammation and pointed to a role of CSF in directing brain invasion by immune cells during EAE.

                                                  Noseworthy et al 2000

The mechanisms for inflammatory blood cells choosing where to cross into the brain or spinal cord parenchyma in MS are unclear. Drugs such as natalizumab, which affect the connection between the active cells and the inflamed lining of the CNS vessels, have an excellent effect in MS relapses. But why some people have more symptoms due to spinal cord disease while others suffer with optic nerve inflammation is not known.

The pattern of inflammation is not the same in EAE and the majority of MSers. It is suprising to see that the brain is a gateway to cells in EAE, as it usually affects the spinal cord the most.

Some people ask whether their vision or their balance will be affected next. Some people wonder why it is only one side of the body that is "bad". Is this important to you?