The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system.
BACKGROUND
The Rho family of small GTPases is responsible for various processes involving actin cytoskeleton in eukaryotic cells, including neurite outgrowth. Several substances found at the peripheral nerve injury site were shown to activate one member of this family, Rho. The activation of Rho leads to neurite outgrowth inhibition and the development of posttraumatic neuropathic pain. The authors used the clinically tested Rho-associated kinase inhibitor fasudil hydrochloride to enhance the functional recovery of the peripheral nerve in the rat.


METHODS
In the peroneal nerve interpositional graft model, the authors administered fasudil (experimental groups) or saline (control groups) (1) intraperitoneally and (2) directly into the graft by microinjection (n = 6 animals per experimental condition). Neural recovery was assessed during postoperative follow-up lasting 80 days by peroneal functional index, electrophysiologic, and histomorphometric analyses.


RESULTS
The peroneal functional index returned to values not significantly different from preoperative values on days 55 (fasudil injected into the graft) and 60 (fasudil injected intraperitoneally) in the experimental groups. In the control groups, this took 70 (saline injected intraperitoneally) and 75 days (saline injected into the graft). These results are supported by electrophysiologic and histomorphologic assessments.


CONCLUSIONS
The authors determined that fasudil hydrochloride was capable of accelerating the functional regeneration after peripheral nerve axotomy, which is consistent with the results of reports about Rho cascade disruption in the central nervous system. Because fasudil hydrochloride is a clinically tested drug, it could be used to enhance neural regeneration in human patients as well.
Madura
Tomas
T
Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. tomas.madura@manchester.ac.uk
Kubo
Tateki
T
Tanag
Marvin
M
Matsuda
Ken
K
Tomita
Koichi
K
Yano
Kenji
K
Hosokawa
Ko
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019771:Axotomy; D004195:Disease Models, Animal; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D017933:Peripheral Nervous System / Q000187:drug effects; D010543:Peroneal Nerve / Q000187:drug effects* / Q000293:injuries; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020196:Trauma, Nervous System / Q000188:drug therapy / Q000601:surgery; D014459:Ulnar Nerve / Q000637:transplantation; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors
D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020741:rho GTP-Binding Proteins; C049347:fasudil