Neuroprotective effects of nitrone radical scavenger S-PBN on reperfusion nerve injury in rats.
The nitrone-based free radical scavengers have potent neuroprotective activities in models of stroke in which oxidative stress plays a key role in its development. We examined the effects of S-PBN (sodium 4-[(tert-butylimino) methyl]benzene-3-sulfonate N-oxide), a spin trap nitrone, on reperfusion injury in rat peripheral nerves. Immediately after the onset of 4-h ischaemia in rat right hindlimb, S-PBN was administered via mini-osmotic pumps, containing 2 ml of S-PBN (1.2 M), inserted subcutaneously. S-PBN, in addition, was given by a single injection (50 mg/kg BW, i.p.). Mean plasma concentrations of S-PBN were significantly greater in S-PBN-treated rats than in controls after 24, 48 and 72 h of reperfusion. Pump and dosing solution analysis indicated that the rats received between 82 and 99% of the target S-PBN concentration. Morphology in sciatic, tibial and peroneal nerves was assessed after 4 h of ischaemia followed by 72 h and 7 days of reperfusion. After 72 h of reperfusion, saline-treated control rats showed endoneurial oedema at the thigh level and diffuse axonal degeneration of myelinated nerve fibres distally. S-PBN-treated nerves were normal or revealed less severe abnormalities in myelinated fibres after 72 h and 7 days of reperfusion, when compared with those in saline-treated control nerves. Morphometrically, the frequency of abnormal myelinated fibres at calf levels was significantly less in S-PBN-treated nerves than in controls. In conclusion, post-ischaemic administration of S-PBN exhibits substantial neuroprotective properties in ischemia/reperfusion nerve injury.
Gray
Chris
C
Department of Pharmacology and Toxicology, University of Otago Medical School, Dunedin 9015, New Zealand.
Nukada
Hitoshi
H
Jackson
David M
DM
McMorran
P Denise
PD
Wu
A
A
Ma
F
F
D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006614:Hindlimb; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C015388:nitrones