Plexin-B2, an axon guidance protein in the central nervous system (CNS), plays an important role in wound healing and neural repair following spinal cord injury (SCI), according to research conducted at the Icahn School of Medicine at Mount Sinai and published today in Nature Neuroscience. The study's findings could aid the development of therapies that target axon guidance pathways for more effective treatment of SCI patients.
Tissue repair after SCI requires the mobilization of immune and glial cells to form a protective barrier that seals the wound, facilitates debris clearing and contains inflammation. Building this barrier involves a process called corralling wherein microglia (immune cells in the CNS) and macrophages (immune cells that originate from blood) form a barrier around the lesion that separates healthy and necrotic tissue. In this study, researchers found that this corralling begins early in the healing process and requires Plexin-B2, a protein that facilitates the movement of immune cells by steering them away from colliding cells.
Researchers found that the deletion of Plexin-B2 in microglia and macrophages impaired corralling, which led to tissue damage, inflammatory spillover, and hindered the regeneration of axons (slender part of a nerve cell where impulses are conducted).
"The role of microglia and macrophages in the spatial organization of glial cells around the injury site via an axon guidance receptor is quite unexpected" said lead investigator Hongyan Jenny Zou, MD, PhD, Professor of Neurosurgery and Neuroscience at the Icahn School of Medicine at Mount Sinai.
Tissue repair in the CNS relies on a coordinated response from diverse cell types in overlapping phases. This complexity makes it difficult to distinguish specific roles of glial cell populations. Previously, astrocytes (supporting glial cells) were presumed to be the main driver for corralling. However, this study identified the critical contribution of injury-activated microglia/macrophages, as well as the role of Plexin-B2 in corralling. Understanding the signaling pathways and interactions of glial cells with each other and the injury environment is fundamental to improving neural repair after a traumatic brain or spinal cord injury.
This research was supported by grants from the National Institutes of Neurological Disorders and Stroke, the Craig H. Neilsen Foundation, the New York State Spinal Cord Injury Research Board, and the National Institute on Aging and the National Institute on Drug Abuse.
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The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care--from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty by U.S. News & World Report.
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