Proteasome inhibition promotes functional recovery after peripheral nerve reperfusion injury.
BACKGROUND
The proteasome degrades NF-kappaB blocking protein (I-kappaB) and activates NF-kappaB that plays as a key transcriptional factor to regulate inflammatory factors that are involved in the tissue reperfusion injury. This study was designed to assess whether the proteasome inhibitor can attenuate peripheral nerve ischemia/reperfusion (I/R) injury and consequently promote motor functional recovery after ischemic insult.


METHODS
Rat sciatic nerves were exposed to 2 hour of ischemia followed by various periods of reperfusion. Rats were administered either proteasome inhibitor (bortezomib) or phosphate-buffered saline 30 minutes before reperfusion start. Results were evaluated using a walking track test, and an isolated muscle contraction test, and by muscle weight, and histology.


RESULTS
Bortezomib treatment induced an earlier improvement in sciatic functional index and a more rapid restoration of contractile force and wet weight of extensor digitorum longus muscle. Bortezomib reduced early axonal degeneration and promoted regeneration.


CONCLUSIONS
This study indicates that bortezomib; a proteasome inhibitor, is effective at promoting the functional recovery of reperfused peripheral nerve. The proteasome inhibition may play a role as one of the clinical strategy in the peripheral nervous system I/R injury with further understanding its mechanism of action.
Park
Jong Woong
JW
Department of Orthopaedic Surgery, College of Medicine, Korea University, Seoul, Korea. ospark@korea.ac.kr
Kim
Kwang Mo
KM
Oh
Kwang Joon
KJ
Rhyu
Im Joo
IJ
Jang
Hyon Seok
HS
D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D005260:Female; D007275:Injections, Intravenous; D007537:Isometric Contraction / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology; D009408:Nerve Compression Syndromes / Q000473:pathology / Q000503:physiopathology; D011292:Premedication; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D012183:Retrograde Degeneration / Q000473:pathology / Q000503:physiopathology; D012584:Sciatic Nerve / Q000098:blood supply* / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects*
D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex