Neurology Central

Immune-brain relationships: new paradigms in searching for treatments for neurodegenerative disease?

For decades, it was believed that due to its unique structure, the brain functions best as an autonomous tissue behind barriers, equipped with mechanisms of homeostasis and repair. Since immune cells are the body’s champions of repair, it was assumed that the brain-resident innate immune cells, the microglia, mediate this function. The microglia enter the CNS during early development [1], and their maturation occurs step-wise, in synchrony with the needs of the developing brain [2]. Yet, most of the body’s other tissues, while containing resident immune cells, require additional systemic immune support for their repair. In contrast, it was believed that the brain escapes from such help, relying solely on its resident immune population. This dogma prevailed for decades. Below, I briefly summarize milestones that paved the way to changes in this commonly accepted view.

Almost all brain pathologies are associated with local inflammation [3], the etiology of which has only recently started to be deciphered. Nevertheless, based on the long-held dogma that the brain is an immune privileged site, attempts were made to use anti-inflammatory drugs to treat brain pathologies in which local inflammation was observed, almost regardless of the primary disease etiology; this approach mostly failed, resulting in much confusion within the research community [4].

Studies initiated by my team over almost two decades have demonstrated that the CNS and the immune system engage in bi-directional communication, and that the brain is dependent on systemic immunity, and not only on the local innate immune-resident cells. The dependence of the brain on systemic immune support was shown with respect to formation of new neurons, cognitive ability [5-7], coping with stress [8], and recently, in social behavior [9].

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