Alpha-lipoic acid provides neuroprotection from ischemia-reperfusion injury of peripheral nerve.
BACKGROUND
Reperfusion aggravates nerve ischemic fiber degeneration, likely by the generation of reduced oxygen species. We therefore evaluated if racemic alpha-lipoic acid (LA), a potent antioxidant, will protect peripheral nerve from reperfusion injury, using our established model of ischemia-reperfusion injury.


METHODS
We used male SD rats, 300+/-5 g. Ischemia was produced by the ligature of each of the supplying arteries to the sciatic-tibial nerve of the right hind-limb for predetermined periods of time (either 3 or 5 h), followed by the release of the ligatures, resulting in reperfusion. LA was given intraperitoneally daily for 3 days for both pre- and post-surgery. Animals received either LA, 100 mg/kg/day, or the same volume of saline intraperitoneally. Clinical behavioral score and electrophysiology of motor and sensory nerves were obtained at 1 week after ischemia-reperfusion. After electrophysiological examination, the sciatic-tibial nerve was fixed in situ and embedded in epon. We evaluated for ischemic fiber degeneration (IFD) and edema, as we described previously.


RESULTS
Distal sensory conduction (amplitude of sensory action potential and sensory conduction velocity (SCV) of digital nerve) was significantly improved in the 3-h ischemia group, treated with LA (P<0.05). LA also improved IFD of the mid tibial nerve (P=0.0522). LA failed to show favorable effects if the duration of ischemia was longer (5-h ischemia).


CONCLUSIONS
These results suggest that alpha-lipoic acid is efficacious for moderate ischemia-reperfusion, especially on distal sensory nerves.
Mitsui
Y
Y
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Schmelzer
J D
JD
Zollman
P J
PJ
Mitsui
M
M
Tritschler
H J
HJ
Low
P A
PA
D000200:Action Potentials; D000818:Animals; D005684:Gait; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain; D011187:Posture; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012584:Sciatic Nerve / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D013979:Tibial Nerve / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology
D018696:Neuroprotective Agents; D008063:Thioctic Acid