Differential patterns of local gene regulation in crush lesions of the rat optic and sciatic nerve: relevance to posttraumatic regeneration

Abstract

Axon regrowth after nerve injury can occur in the peripheral but fails in the central nervous system. Cellular reactions at the lesion site affect axonal regrowth. We compared gene regulation in optic nerve (ON) and sciatic nerve (SN) crush lesions in adult rats by cDNA array analysis, quantitative RT-PCR and immunohistochemistry, focusing on the primary lesion site rather than the proximal or distal nerve stump. Four days after injury, identical gene regulation in ON and SN lesions was found for 19/1185 genes (15 up, 4 down). In contrast, tissue-specific regulations were identified for 48 genes in ON and 50 genes in SN crush lesions. Among these, in the ON many genes were downregulated (23 up, 25 down) whereas upregulation predominated in SN lesions (43 up, 7 down), especially for signaling, metabolism, and translation/transcription-related genes. In ON lesions aquaporin 4 downregulation corresponded to a transient loss of astrocytes. Tissue-type plasminogen activator was upregulated in the lesion and distal stump of SN while the urokinase-type plasminogen activator was upregulated only in the ON lesion indicating differences in local proteolysis between the systems. Typical neuronal genes were regulated at the crush site comprising neurotransmitter genes in ON and actin cytoskeleton-related genes in the SN. The differential orchestration of local gene regulation has implications for axonal regeneration in central nervous system lesions.