Alpha-lipoic acid provides neuroprotection from ischemia-reperfusion injury of peripheral nerve
Introduction
Ischemic injury to peripheral nerve is aggravated by reperfusion, resulting in lipid peroxidation and fiber degeneration [1], [2]. In other tissues, including brain, the major mechanism of reperfusion injury is considered to be due to reduced oxygen species [3]. α-Lipoic acid (LA) is a powerful lipophilic antioxidant in vitro and in vivo [4]. It is reported to be efficacious in the experimental ischemia-reperfusion injury in brain [5], [6], [7], heart [8], [9] and in experimental diabetic neuropathy [10], [11], where oxidative stress is present. We therefore evaluated if LA will ameliorate ischemia-reperfusion (IR) injury of peripheral nerve subjected to different durations of ischemia followed by reperfusion. We used our established model of IR injury [12].
Section snippets
Animals
We used 44 male Sprague–Dawley rats weighing 300±5 g.
Surgery
The surgical procedure for producing IR injury has been previously detailed. In essence we ligated each of the supplying arteries to the sciatic-tibial nerve of the right hind-limb for predetermined periods of ischemia (either 3 or 5 h), followed by reperfusion, resulting from the release of the ligatures.
The rat was anesthetized with intraperitoneal pentobarbital (60 mg/kg). Additional doses of pentobarbital were used if anesthesia lightened
Behavioral score
The behavioral score for 3-CONT and 3-LA were 5.8±0.8 and 7.8±1.0, respectively (Fig. 1A). The behavioral score for 5-CONT and 5-LA were 2.5±0.8 and 3.8±0.7, respectively (Fig. 1B). Behavioral score was consistently normal (11.0) for contralateral side. The improvement with LA did not reach statistical significance.
Electrophysiology
In the present study, the results of the amplitude of nerve compound action potential was expressed as a percentage of the left side. For SCV, we used absolute values of m/s. The
Discussion
The main findings of the present study are that LA provided some neuroprotection of peripheral nerve from ischemia-reperfusion injury (IR injury) in nerves subjected to 3 h of ischemia, but failed to do so in those subjected to 5 h of ischemia. Treatment with LA significantly improved distal sensory conduction in the group subjected to 3 h of ischemia. In contrast, LA treatment did not improve CMAP in the 3-h ischemia group (3-LA). In the pathological studies, IFD grade at mid tibial nerve
Acknowledgments
Supported in part by grants from NINDS (NS22352) and Mayo funds.
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