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Abstract #28020 Published in IGR 13-1
Recruitment of monocytes are needed for neuroprotection and repair
Schwartz MRestorative Neurology and Neuroscience 2010; 28: 610
For decades, the central nervous system (CNS) was viewed as an autonomous unit, nourished by the blood, and shielded from pathogens and toxins present in the circulation. In addition, since it is equipped with its own innate immune cell population, the microglia, which was believed to be capable of fully providing the brain's needs for defense and protection, any further infiltration of bloodmacrophageswas viewed as a sign of pathology that should be mitigated. Based on a decade of experimental evidence showing that the peripheral immune cells (both CD4+ T cells that recognize brain antigens, and bloodmonocytes) are needed for brain plasticity in health and disease, and through an understanding of howandwhere this immune support occurs, our group has proposed that the central nervous system (CNS) is critically dependent on these peripheral immune cells for neuronal survival and repair, for neurogenesis and oligodendrogenesis from resident neural stem cells, for coping with a stressful environment, and for fighting off acute and chronic neurodegenerative conditions. Insufficient immunity or its malfunction can impact cognitive performance, resilience to stress, emergence of developmental neuropsychological disorders (e.g., Schizophrenia), and the onset and progression of neurodegenerativediseases such asAlzheimer's disease, glaucoma, agerelated dementia, and ALS. Boosting of peripheral immunity under pathological conditions including acute CNS trauma, Alzheimer's disease, depression, and glaucoma was found to be an effectivemeans of enhancing recruitment ofmonocytes that locally displayed a distinctive role than activated resident microglia. These monocytes locally displayed an antiinflammatory phenotype (also known as M2 or 'alternativelyactivated macrophages'). Such macrophages in turn terminated the microglia response and contributed to a scar resolution. In Alzheimer's disease, vaccination with weak antigens resulted in recruitment of monocytes that modified the local milieu in terms of cytokine profile and growth factor composition. Taken together, our results suggest that blood monocytes are key players of neuroprotection and neurorepair; their effect reflects timing, context and location. The limited recruitment will be discussed.
M. Schwartz. Weizmann Institute of Science, Rehovot, Israel.
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
