Trehalose enhances macrophage autophagy to promote myelin debris clearance after spinal cord injury.

Background: Myelin-laden foamy macrophages accumulate extensively in the lesion epicenter, exhibiting characteristics of autophagolysosomal dysfunction, which leads to prolonged inflammatory responses after spinal cord injury (SCI). Trehalose, known for its neuroprotective properties as an autophagy inducer, has yet to be fully explored for its potential to mitigate foamy macrophage formation and exert therapeutic effects in the context of SCI.

Results: We observed that trehalose significantly enhances macrophage phagocytosis and clearance of myelin in a dose-dependent manner in vitro.

Fingolimod (FTY720) Hinders Interferon-γ-Mediated Fibrotic Scar Formation and Facilitates Neurological Recovery After Spinal Cord Injury.

Following spinal cord injury (SCI), fibrotic scar inhibits axon regeneration and impairs neurological function recovery. It has been reported that T cell-derived interferon (IFN)-γ plays a pivotal role in promoting fibrotic scarring in neurodegenerative disease. However, the role of IFN-γ in fibrotic scar formation after SCI has not been declared.

Corrigendum: TAZ induces migration of microglia and promotes neurological recovery after spinal cord injury.

[This corrects the article DOI: 10.3389/fphar.2022.

TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury.

Following spinal cord injury (SCI), microglia gradually migrate to the edge of the lesion, interweaving around the border of the lesion to form the microglial scar, which performs inflammatory limiting and neuroprotective functions. Recent reports showed that Yes-associated protein (YAP) was expressed in astrocytes and promoted the formation of astrocytic scars, while YAP was not expressed in microglia after SCI. YAP and its paralogue transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, which have a similar functional role as both are negatively regulated by the Hippo signalling pathway.

D-4F, an apolipoprotein A-I mimetic, promotes the clearance of myelin debris and the reduction of foamy macrophages after spinal cord injury.

After spinal cord injury (SCI), a large number of blood-derived macrophages infiltrate the lesion site and phagocytose myelin debris to become foamy macrophages, which leads to chronic inflammation. The drug D-4F, an apolipoprotein A-I peptidomimetic made of D-amino acids, has been reported to promote the lipid metabolism of foamy macrophages in atherosclerosis. However, the role and mechanism of D-4F in SCI are still unclear.

SU16f inhibits fibrotic scar formation and facilitates axon regeneration and locomotor function recovery after spinal cord injury by blocking the PDGFRβ pathway.

Background: Excessively deposited fibrotic scar after spinal cord injury (SCI) inhibits axon regeneration. It has been reported that platelet-derived growth factor receptor beta (PDGFRβ), as a marker of fibrotic scar-forming fibroblasts, can only be activated by platelet-derived growth factor (PDGF) B or PDGFD. However, whether the activation of the PDGFRβ pathway can mediate fibrotic scar formation after SCI remains unclear.

Myelin Debris Impairs Tight Junctions and Promotes the Migration of Microvascular Endothelial Cells in the Injured Spinal Cord.

Clearance of myelin debris caused by acute demyelination is an essential process for functional restoration following spinal cord injury (SCI). Microvascular endothelial cells, acting as "amateur" phagocytes, have been confirmed to engulf and degrade myelin debris, promoting the inflammatory response, robust angiogenesis, and persistent fibrosis. However, the effect of myelin debris engulfment on the function of endothelial tight junctions (TJs) remains unclear.

M1 macrophages impair tight junctions between endothelial cells after spinal cord injury.

After spinal cord injury (SCI), endogenous angiogenesis occurs in the injury core, unexpectedly accompanied by continuous leakage of the blood-spinal cord barrier (BSCB), which may be caused by destruction of the tight junctions (TJs) between vascular endothelial cells-an important structure of the BSCB. Blood-derived macrophages infiltrate into the spinal cord, aggregate to the injury core and then polarize toward M1/M2 phenotypes after SCI. However, the effect of macrophages with different polarizations on the TJs between vascular endothelial cells remains unclear.

Fibrotic Scar After Spinal Cord Injury: Crosstalk With Other Cells, Cellular Origin, Function, and Mechanism.

The failure of axonal regeneration after spinal cord injury (SCI) results in permanent loss of sensorimotor function. The persistent presence of scar tissue, mainly fibrotic scar and astrocytic scar, is a critical cause of axonal regeneration failure and is widely accepted as a treatment target for SCI. Astrocytic scar has been widely investigated, while fibrotic scar has received less attention.