Theory How Cells enter the Brain

Ogura H, Arima Y, Kamimura D, Murakami M. The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier. Biomed J. 2013;36:269-73.
The inflammation amplifier, a nuclear factor-kappa B (NF-kB)feedback loop in non-immune cells including fibroblasts and endothelial cells, describes how NF-kB-mediated transcriptions are enhanced to induce the inflammation in the presence of signal Tranducer and Activator of Transcription 3 (STAT3) activation. It was originally discovered in rheumatoid arthritis and multiple sclerosis mouse models and has since been shown to be associated with various human diseases and disorders including autoimmune diseases, metabolic syndromes, neurodegenerative diseases, and other inflammatory diseases. The amplifier begins with IL-17, which acts as the main signal to express NF-kB-mediated transcriptions, and IL-6, an NF-kB target, which functions as a fuel for the inflammation amplifier. Indeed, other NF-kB targets including various chemokines also act as effector molecules that cause local accumulation of various immune cells and subsequent inflammation. Through extensive studies in the multiple sclerosis model experimental autoimmune encephalomyelitis, we recently demonstrated that regional neural activation induces excess activation of the inflammation amplifier at specific blood vessels in the fifth lumbar cord, creating a gateway for immune cells to enter the central nervous system (CNS). We thus propose the gateway theory to describe how regional neural activation enables immune cells to enter the CNS from the blood and argue that this theory might provide novel therapeutic targets for inflammatory diseases and disorders.

There was a view posted recently that there has been 50 years of EAE theories, so here's another.

It suggests that neural activation, like the effects of gravity on the legs, cause neural activity and a local inflammatory amplifying loop that then cause the opening of the blood brain barrier that acts like a gate to allow cells into the brain.

Do cells really start entering at L5 and flood into the rest of the brain and spinal cord ?(click here)

  

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