Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after Spinal Cord Injury

Spinal cord injuries often lead to scar formation, hindering tissue repair. This study reveals that excess cholesterol, specifically from myelin, accumulates in spinal cord lesions of young adult mice and is not efficiently cleared. Unlike the central nervous system, the peripheral nervous system efficiently removes excess cholesterol through reverse cholesterol transport (RCT). When RCT is prevented in peripheral nerves, it leads to macrophage accumulation and fibrosis. In neonatal mice, spinal cord lesions typically heal without scar formation because they lack myelin-derived lipids. However, introducing myelin into these lesions disrupts healing, causing cholesterol accumulation, macrophage activation, and fibrosis.

• 1
  Cholesterol crystals accumulate in spinal cord lesions of young adult mice as early as 7 days post-injury, persisting for at least 6 weeks.
• 2
  Excess cholesterol accumulation in spinal cord lesions is associated with the activation of the NLRP3 inflammasome, which promotes inflammation.
• 3
  Myelin phagocytosis suppresses macrophage apoptosis by increasing CD5L expression, which contributes to the persistence of macrophages in the lesion site.