Alpha-lipoic acid provides neuroprotection from ischemia-reperfusion injury of peripheral nerve

被引:71
作者
Mitsui, Y
Schmelzer, JD
Zollman, PJ
Mitsui, M
Tritschler, HJ
Low, PA
机构
[1] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA
[2] Asta Medica, Frankfurt, Germany
关键词
ischemia-reperfusion injury; peripheral nerve; oxidative stress; alpha-lipoic acid; neuroprotection; sensory conduction velocity; ischemic fiber degeneration;
D O I
10.1016/S0022-510X(99)00017-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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). Conclusion: These results suggest that alpha-lipoic acid is efficacious for moderate ischemia-reperfusion, especially on distal sensory nerves. (C) 1999 Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:11 / 16
页数:6
相关论文
共 25 条
[1]   Carbonyl histochemistry in rat reperfusion nerve injury [J].
Anderson, GM ;
Nukada, H ;
McMorran, PD .
BRAIN RESEARCH, 1997, 772 (1-2) :156-160
[2]   The pharmacology of the antioxidant lipoic acid [J].
Biewenga, GP ;
Haenen, GRMM ;
Bast, A .
GENERAL PHARMACOLOGY, 1997, 29 (03) :315-331
[3]   Effects of α-lipoic acid on neurovascular function in diabetic rats:: interaction with essential fatty acids [J].
Cameron, NE ;
Cotter, MA ;
Horrobin, DH ;
Tritschler, HJ .
DIABETOLOGIA, 1998, 41 (04) :390-399
[4]   THE FREE-RADICAL SCAVENGER, ALPHA-LIPOIC ACID, PROTECTS AGAINST CEREBRAL ISCHEMIA-REPERFUSION INJURY IN GERBILS [J].
CAO, XH ;
PHILLIS, JW .
FREE RADICAL RESEARCH, 1995, 23 (04) :365-370
[5]   REGULATION OF RAT NERVE BLOOD-FLOW - ROLE OF EPINEURIAL ALPHA-RECEPTORS [J].
KIHARA, M ;
LOW, PA .
JOURNAL OF PHYSIOLOGY-LONDON, 1990, 422 :145-152
[7]   INCREASED ENDONEURIAL FLUID PRESSURE IN EXPERIMENTAL LEAD NEUROPATHY [J].
LOW, PA ;
DYCK, PJ .
NATURE, 1977, 269 (5627) :427-428
[8]   The roles of oxidative stress and antioxidant treatment in experimental diabetic neuropathy [J].
Low, PA ;
Nickander, KK ;
Tritschler, HJ .
DIABETES, 1997, 46 :S38-S42
[9]   EFFECTS OF CHANGES OF BLOOD-PRESSURE, RESPIRATORY-ACIDOSIS AND HYPOXIA ON BLOOD-FLOW IN THE SCIATIC-NERVE OF THE RAT [J].
LOW, PA ;
TUCK, RR .
JOURNAL OF PHYSIOLOGY-LONDON, 1984, 347 (FEB) :513-524
[10]  
MCCORD JM, 1985, NEW ENGL J MED, V312, P159