Emerging Concepts in Myeloid Cell Biology after Spinal Cord Injury

Abstract

Summary: Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been adequately defined. In general, the dynamics and composition of myeloid cell recruitment to the injured spinal cord are consistent between mammalian species; only the onset, duration, and magnitude of the response vary. Emerging data, mostly from rat and mouse SCI models, indicate that resident and recruited myeloid cells are derived from multiple sources, including the yolk sac during development and the bone marrow and spleen in adulthood. After SCI, a complex array of chemokines and cytokines regulate myelopoiesis and intraspinal trafficking of myeloid cells. As these cells accumulate in the injured spinal cord, the collective actions of diverse cues in the lesion environment help to create an inflammatory response marked by tremendous phenotypic and functional heterogeneity. Indeed, it is difficult to attribute specific reparative or injurious functions to one or more myeloid cells because of convergence of cell function and difficulties in using specific molecular markers to distinguish between subsets of myeloid cell populations. Here we review each of these concepts and include a discussion of future challenges that will need to be overcome to develop newer and improved immune modulatory therapies for the injured brain or spinal cord.

IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury

“…This is due, in part, to the release of numerous mediators from microglia and macrophages that exert cytotoxic effects on CNS cells that can lead to demyelination and neuronal loss Hawthorne and Popovich 2011;Ren and Young 2013). Nevertheless, these cells also produce a variety of factors that promote cell survival and tissue healing, and under certain circumstances, may lead to protective effects in the injured CNS Popovich and Longbrake 2008).…”

Chemokines in CNS injury and repair

“…Chemokine gradients are argued to persist indefinitely or to reoccur periodically, in order to explain the observation of infiltrated for long periods, namely about 6 weeks for neutrophils and over 6 months for monocytes, in the lesioned spinal cord, despite their short lifespan of roughly 5 days and 2 months, respectively (Pillay et al 2010;Hawthorne and Popovich 2011). The rapid and transient induction of several chemokines, for example, CCL2, CCL21 and CXCL10, in neurons has recently been shown to precede the induction of these chemokines in astrocytes, although the latter are considered the major source of chemokines after CNS injury (de Haas et al 2007).…”

Impact of Prenatal Immune System Disturbances on Brain Development

“…In cases of MS or other demyelinating conditions, it has been shown that there exists a subset of microglia at the site of demyelination that can recruit oligodendrocyte precursor cells and phagocytose damaged neurons (Olah et al, 2011). In SCI, cells of the myeloid origin have been shown to play a role in intraspinal trafficking past the injury (Hawthorne and Popovich, 2011).…”