Rho-kinase inhibition enhances axonal regeneration after peripheral nerve injury

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J Peripher Nerv Syst. 2006 Sep;11(3):217-24.

Rho-kinase inhibition enhances axonal regeneration after peripheral

nerve injury.

Hiraga A, Kuwabara S, Doya H, Kanai K, Fujitani M, Taniguchi J, Arai

K, Mori M, Hattori T, Yamashita T.

Department of Neurobiology; Department of Neurology, Chiba University

Graduate School of Medicine; and Department of Neurology, National

Hospital Organization Chiba-East National Hospital, Chiba, Japan.

In injured adult neurons, the process of axonal regrowth and

reestablishment of the neuronal function have to be activated. We

assessed in this study whether RhoA, a key regulator of neurite

elongation, is activated after injury to the peripheral nervous

system.

RhoA is activated in motoneurons but not in Schwann cells after mouse

sciatic nerve injury. To examine whether the activation of RhoA and

its effector, Rho-kinase, retards axon regeneration of injured

motoneurons, we employed a Rho-kinase inhibitor, fasudil. Amplitudes

of distally evoked compound muscle action potentials are increased

significantly faster after axonal injury in mice treated with fasudil

compared with controls.

Histological analysis shows that fasudil treatment increases the

number of regenerating axons with large diameter, suggesting that

axon maturation is facilitated by Rho-kinase inhibition. In addition,

fasudil does not suppress the myelination of regenerating axons.

These findings suggest that RhoA/Rho-kinase may be a practical

molecular target to enhance axonal regeneration in human peripheral

neuropathies.