سید عبدالرحیم رضایی

The retrograde neuronal death in the dorsal root ganglia (DRG) can be the main factor in poor regeneration of injured peripheral nerves occurring by increased activity of oxidant agents. The present study investigated the effect of thiamine treatment, as an antioxidant, on neuronal death after sciatic nerve transection.

Twenty-five male Wistar rats were allocated in 5 experimental groups (n = 5). Group 1 was considered as intact. The sciatic nerve was transected in groups 2 to 5. Then rats were treated daily with physiological saline (control group), thiamine (50 and 100 mg/kg; i.p.) and thiamine (1.7 mg/kg locally). After four weeks, animals were sacrificed and L5DRG was removed for histological assessment.

Morphological analysis showed some no cell areas in L5DRG sections, which may be related to apoptotic cells in axotomized animals. L5DRG volume measurement showed no significant difference between intact and local thiamine treated group, while its volume was significantly reduced in other experimental groups (p < 0.001). This parameter was also significantly reduced in control group compared with local thiamine treated group (p < 0.001). Although the difference of L5DRG cell number in local thiamine treated group was not significant, its reduction was significant in control and intraperitoneal groups compared with intact group (p < 0.01). The L5DRG cell count in local thiamine treated group was significantly higher than that in control group (p < 0.01).

These findings may indicate that thiamine if is administered in sufficient doses can be classified as neuroprotective agent.

Regeneration of nerve fibers in transected nerve injuries requires formation of growth cone and axonal sprouting, proliferation of Schwan cells, myelin synthesis and etc. Pharmacological interventions are recommended to improve and promote these processes. In the present study the effects of thiamine, dexamethasone and N-acetyl cysteine administrations on axonal sprouting are examined.

After transection of right sciatic nerve of 24 male Wistar rats, the two ends of cut nerve were sutured into a piece of silicone tube. The rats were then divided into four groups (n = 6); receiving N-acetyl cysteine (150 mg/kg), dexamethasone (0.2 mg/kg), thiamine (50 mg/kg) and normal saline (control) once daily by intraperitoneal injection. At the end of treatment period (16 weeks) animals were sacrificed and the axonal sprouts removed and histologically examined.

There was no significant difference in the number of nerve fibers, axonal diameter and myelin sheath thickness among experimental groups. However, axonal diameter was almost increased in thiamine treated group (p=0.06). Moreover, a significant decrease (p < 0.05) in nerve cross sectional area was observed in dexamethasone group. The axonal diameter and myelin sheath thickness were also significantly decreased (p < 0.05) in dexamethasone group, compare to thiamine group.

Our data indicate that sciatic nerve regeneration in rats is inhibited by dexamethasone, might be ameliorated by thiamine, and is not changed by N-acetyl cysteine.

Wallerian degeneration is aninnate immune response which occurs after nerve injury. In this study, the effects of dexamethasone (Dex) and thiamine (Thi), as anti-inflammatory drugs, were compared on the Wallerian degeneration.

The right sciatic nerve of 45 male rats was transected and the rats were divided into five groups (n=9). Animals in groups 2 to 5 daily received (i.p) low and high doses of Dex and Thiup until sampling days, respectively. Group 1 was considered as control. At 5th, 7th and 10th days after axotomy, 3 rats from each group were killed and the distal stump of sciatic nerve was served for histological assessment.

In the histological examinations of all groups, edema, degraded myelin sheets and some infiltrated mononuclear cells were observed. But administration of high doses of Dex and Thi (groups 4 and 5) alleviated all the above mentioned histological changes. In comparison with control group, the groups received high doses of Dex and Thi showed significant increase in the number of myelinated nerve fibers (p<0.05). Measuring of the cross surface area of the sciatic nerve showed no significant differences. Finally, administration of high dose of Dex was associated with several side effects.

Although these findings indicated the beneficial effects of both Dex and Thi but due to the severe adverse effects of Dex, it is recommended to prescribe Dex for acute and short term cases of nerve injuries, whereas in the case of chronic and long terminflammatory conditions Thi administration may be preferred.