Central Nervous System Injury–Induced Repulsive Guidance Molecule Expression in the Adult Human Brain

Background

The repulsive guidance molecule (RGM) is involved in formation of the central nervous system during development by moderating the repulsion of growing axons. However, the role of RGM in adult central nervous system lesions remains to be clarified.

Objective

To identify and determine RGM expression in adult brains with focal cerebral ischemia or traumatic brain injury and in neuropathologically unaffected control brains.

Patients

Twenty-one brains of patients with focal cerebral ischemia, 25 brains after traumatic brain injury, and 4 control brains.

Main Outcome Measure

Expression of RGM as assessed by immunohistochemical analysis.

Results

In normal brains, RGM expression was detected on the perikarya of some neurons, choroid plexus, smooth muscle and endothelial cells, oligodendrocytes, and myelinated white matter fibers. After focal cerebral ischemia and traumatic brain injury, RGM-immunopositive cells accumulated in lesional and perilesional areas. In hemorrhagic lesions, a massive accumulation of RGM-immunopositive cells was observed. During the first week after insult, RGM expression remained confined to neurons, smooth muscle and endothelial cells, and leukocytes infiltrating the lesion. Thereafter, with maturation of the lesion, we observed RGM expression by components of the developing scar tissue, such as fibroblastoid cells, reactive astrocytes, and a pronounced extracellular RGM deposition resembling neo-laminae.

Conclusions

This is the first study of RGM in the human central nervous system. Following central nervous system injury, RGM, a novel, potent axonal growth inhibitor, is present in axonal growth impediments: the mature myelin, choroid plexus, and components of the developing scar.