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Lithium Improves Regeneration after Sciatic Nerve Traumatic Injury in Rat
26 November 2008 (online)
Lithium (Li) is widely used in the treatment of bipolar mood disorder, and a growing body of evidence considers the neuroprotective effects of Li. Li treatment showed neuroprotection in transient focal cerebral ischemia and improved cerebral blood flow and neurological outcome in previous studies.
Different underlying mechanisms have been proposed for neuroprotective effects of Li, including inactivation of N-methyl-D-aspartate receptors, activation of the phosphatidylinositol 3-kinase-Akt cell survival pathway, enhanced expression of cytoprotective Bcl-2, and inhibition of glycogen synthase kinase-3. The studies cited have addressed neural ischemic injuries, and a lack of information on traumatic injuries is felt. In this pilot study, we assessed the effect of Li by using a crush injury method in rats.
To this purpose, 10 Sprague-Dawley male rats weighing 250 to 350 g were randomly divided into two groups: control group (received distilled water) and Li-treated group (40 mg/kg). One hour before the operation, the proper solution, distilled water or Li, was injected intraperitoneally. All animals were anesthetized with intraperitoneal injection of ketamine (50 mg/kg) and xylazine (5 mg/kg). An incision was made on the dorsum of the thigh and dissecting through the muscles, the sciatic nerve was exposed, and then 15 mm proximal to its trifurcation at the knee level, a Yasargil aneurysm clip (excreting 1.24 N force) was placed and left in situ for 1 minute. Then the incision was closed appropriately and the animals were allowed to recover. Four weeks later, each animal's behavioral score was assessed based on gait, grasp, paw position, and pinch sensitivity. The score for each index was based on a scale of 0 (no function) to 3.0 (normal function) except for pinch sensitivity ranging from 0 to 2. Then the sciatic nerve was fixed in situ for 30 minutes using 4% formaldehyde in phosphate buffer (pH adjusted to 7.4) and then it was removed from 2 mm proximal to the site of crush to 2 mm distal to the site of trifurcation. Tissue samples were fixed in formaldehyde (4%), embedded in paraffin, and longitudinal sections were stained with hematoxylin and eosin.
Light microscopic studies showed Wallerian degeneration in both groups, although Li-treated group demonstrated noticeable reduction in vascularization and more evidences of regeneration. However, no statistically significant differences in neurological function were detected between the two groups by using the Mann-Whitney U test.
Limb-penetrating traumas are commonly associated with nerve injuries. Our findings provide new evidence for the neuroprotective role of Li in peripheral nerve traumatic injuries. More studies to evaluate dose and time responses and to clarify the underlying mechanisms of Li-related neuroprotection are needed.
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Ahmad Reza Dehpour, Ph.D.
School of Medicine, Tehran University of Medical Sciences
PO Box 13145-784, Tehran, Iran