The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain

Abstract

The cortical stab injury has been widely used for biochemical analysis of molecular changes following CNS injury. However, the cellular responses to this injury have not been accurately quantified. In order to provide a baseline for biochemical studies and future experiments on the manipulation of the CNS injury response we have undertaken a quantitative analysis of this injury. The proliferative and reactive responses of oligodendrocyte precursor cells, astrocytes and microglia were measured, using antibodies to NG2, glial fibrillary acidic protein (GFAP) and the cd11-b clone OX-42 to characterise these cell types at 2, 4, 7 and 14 days post-injury. Oligodendrocyte precursors and microglia proliferated rapidly during the first week, mostly within 0.3 mm of the lesion. Of the dividing cells over 60% were oligodendrocyte precursor cells with microglia making up the balance of the dividing cells. Minimal numbers of astrocytes divided in response to the lesion. Large cells with one or two short processes that were both NG2 and OX-42 positive were identified very close to the lesion at 2 and 4 days post-lesion but not thereafter. They are likely to be blood-derived cells that express NG2 or have ingested it. NG2 immunohistochemistry and platelet-derived growth factor α receptor (PDGFα-R) in situ hybridisation on neighbouring sections was performed. In the lesioned area only 12% of NG2 positive (+ive) cells were PDGFα-R +ive (a ratio of 1:8 for PDGFα-R +ive cells: NG2 +ive cells) compared with 33% in the unlesioned cortex and an almost 100% overlap in the spinal cord.