Identification and analysis of genes induced in peripheral nerve after axotomy using cDNA microarrays

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It is generally known that injured peripheral axons regenerate successfully as oppose to central axons. However, complete functional recovery is rarely achieved. To solve this problem, we identified 500 genes induced in peripheral nerve after axotomy using cDNA microarrays in a previous study. The purpose of this project was to analyze the precise function of these genes. The main findings were as follows. 1. Sciatic nerve injury models were created on the p21 knock out mice and it was found that p21, which is a potent Rho kinase inhibitor, regulates radial growth of regenerating axons, thereby promoting functional recovery. Hyperphosphorylation of the neurofilament heavy chain subunits was considered to be the main reason for the impaired radial growth in the p21 knock out mice. 2. The clinically tested Rho-associated kinase inhibitor fasudil hydrochloride was applied to rat peroneal nerve injury models. After injury, significantly accelerated functional recovery was achieved in the fasudil treated animals as compared with control animals. 3. The mRNA expression changes of Slit-Robo signal molecules, known as axonal guidance cues, were examined using in situ hybridization. After transection of a rat facial nerve, up-regulation of slitl expression and down-regulation of slit2 expression were found in the facial nucleus. In contrast, both expressions were up-regulated in the distal Schwann cells.