Pericytes Act as Key Players in Spinal Cord Injury

Abstract

Spinal cord injury results in locomotor impairment attributable to the formation of an inhibitory fibrous scar, which prevents axonal regeneration after trauma. The scarcity of knowledge about the molecular and cellular mechanisms involved in scar formation after spinal cord lesion impede the design of effective therapies. Recent studies, by using state-of-the-art technologies, including genetic tracking and blockage of pericytes in combination with optogenetics, reveal that pericyte blockage facilitates axonal regeneration and neuronal integration into the local neural circuitry. Strikingly, a pericyte subset is essential during scarring after spinal cord injury, and its arrest results in motor performance improvement. The arising knowledge from current research will contribute to novel approaches to develop therapies for spinal cord injury. We review novel advances in our understanding of pericyte biology in the spinal cord.

Figure 1

The role of pericytes in scarring in the injured spinal cord. Pericytes are present surrounding the spinal cord vasculature. The study by Dias et al now suggests a new function for pericytes after spinal cord injury. Blockage of a pericyte subset in the injured spinal cord microenvironment reduces fibrotic scar tissue formation, promotes axonal regeneration, and improves functional recovery. The authors used optogenetic stimulation to show that corticospinal tract axons were regenerated in animals with pericyte-derived scarring attenuation.

Figure 2

Pericytes contribute to the scar formation that inhibits neuronal regeneration. The reduction of pericytic activation attenuates fibrotic tissue formation, facilitating serotonergic and corticospinal axonal regeneration and improving sensorimotor functionality.

Figure 3

Multiple cell populations have been implicated as the origin of fibrous tissue–producing cells. Deposition of extracellular matrix proteins occurs, after injury, during a prolonged period. The fibrous tissue formation, characterized by excessive connective tissue, becomes detrimental, leading to the loss of tissue architecture and organ failure. Multiple cell populations have been implicated as the origin of fibrous tissue–producing cells, including pericytes, endothelial cells, epithelial cells, and resident fibroblasts.