Secondary damage caused by CD11b+ microglia following diffuse axonal injury in rats

Diffuse axonal injury (DAI) is one of the most common and important pathologic features of human traumatic brain injury, accounting for high mortality and the development of persistent posttraumatic neurologic sequelae. Secondary damage resulting, e.g., from mass compressive effects through edema or inflammation can exacerbate morphologic changes in injured axons.

In this study, DAI was induced in Sprague-Dawley rats by subjecting the animals to a midline closed-skull strike. Experimental rats and control animals subjected to sham operation were killed at 0 hour, 1 hour, 3 hour, 6 hour, 12 hour, 24 hour, 72 hour, 5 days, or 7 days later. Brains were harvested and paraffin-embedded sections of brain tissue (5 µm thick) were processed for hematoxylin and eosin staining, Bielschowsky silver staining, cresyl violet staining of Nissl bodies, Weil staining of myelin sheaths, or TUNEL assay to verify neuronal changes. Immunocytochemistry was used to examine the expression of [beta]-amyloid precursor protein, CD11b, and interleukin (IL)-6.

CD11b/IL-6 expression was higher at 6 hour and peaked at 12 hour after injury. Pathologic changes in neurons were greater at 24 and 48 hour after injury. The results indicate that DAI can induce activation of microglia to express IL-6 in the early stages after injury.

This suggests that microglia play an important role in secondary pathologic changes in brain tissue that are mediated, at least in part, by IL-6.