Nonresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury

After a spinal cord injury (SCI), inflammatory macrophages infiltrate the spinal cord and remain at elevated densities around the lesion chronically. This study investigates whether persistent neuroinflammation functions as a sustained barrier that chronically impairs axon regeneration. The research uses a drug (PLX-5622) to deplete microglia and macrophages in mice with chronic SCI. It also uses gene therapy (PTEN-KO) to stimulate axon growth, observing how these interventions affect axon regeneration within the spinal cord lesion. The key finding is that sustained inflammation in the chronic SCI environment may act as a barrier to axon regeneration. The study also shows that the body actively maintains increased densities of macrophages in the injured spinal cord.

• 1
  Macrophages and microglia repopulate the chronically injured spinal cord after depletion, indicating a homeostatic mechanism maintaining their presence.
• 2
  Colony-stimulating factor-1 receptor (CSF1R) antagonism in chronic spinal cord injury augments the growth of specific axon types (5-HT+ and CGRP+) in the lesion.
• 3
  CSF1R antagonism does not augment a phosphatase and tensin homolog protein knock-out–induced functional recovery, suggesting that the observed axon growth is independent of PTEN-KO.