Rapamycin Accelerates Axon Regeneration Through Schwann Cell-mediated Autophagy Following Inferior Alveolar Nerve Transection in Rats.

Sensory disturbance in the orofacial region owing to trigeminal nerve injury is caused by dental treatment or accident. Commercially available therapeutics are ineffective for the treatment of sensory disturbance. Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. Thus, we investigated the therapeutic effects of rapamycin on the sensory disturbance in the mandibular region caused by inferior alveolar nerve (IAN) transection (IANX) in rats. The expression levels of the phosphorylated p70S6K, a downstream molecule of mTOR, in the proximal and distal stumps of the transected IAN were significantly reduced by rapamycin administration to the injured site. Conversely, the increments of both Beclin 1 and microtubule-associated protein-1 light chain 3-II protein levels in the proximal and distal stumps of the transected IAN was induced by rapamycin administration. Immunohistochemical analyses revealed that Beclin 1 was located in Schwann cells in the proximal stump of the IAN. Accumulation of myelin protein zero and myelin basic protein in the proximal and distal stumps of the IAN was significantly reduced by rapamycin administration. Rapamycin administration facilitated axon regeneration after IANX and increased the number of brain-derived neurotrophic factor positive neurons in the trigeminal ganglion. Thus, recovery from sensory disturbance in the lower lip caused by IANX was markedly facilitated by rapamycin. These findings suggest that rapamycin administration is a promising treatment for the sensory disturbance caused by IANX.

Comparative Study of the L5 Spinal Nerve Transection Model and Sciatic Nerve Axotomy Model as a Peripheral Nerve Injury Model in Rat / 체질인류학회지

The aim of this study was to propose new more reliable peripheral nerve transection model to overcome the defect of the traditional sciatic axotomy model by specifically transecting L5 spinal nerve just after emerging from the intervertebral foramen and confining analysis area to the L5 spinal segment. The adult male Sprague-Dawley rats, weighing 300~350 g at the time of surgery, were used for the experiments. Four different experimental groups were used. 1. Sciatic nerve transection (Sc-Tx) group: transect the sciatic nerve in the popliteal fossa where it divided into the common peroneal nerve and tibial nerve. 2. L5 spinal nerve transection (L5-Tx) group: L5 spinal nerve was specifically transected. 3. Suture (Su) group: L5 spinal nerve was transected and immediately sutured. 4. Control group: the same surgical procedure with L5 spinal nerve transection group was performed except for the excision of L5 spinal nerve. To distinguish L5 motoneurons from the other level ones, the animals were received the retrograde tracer, FluoroGold into the axotomized proximal nerve stump. Serial coronal frozen sections at 40 microm thick through the L4 to L6 spinal segment was performed and the resultant total number of sections was about 180. Approximate serial 50 sections (approximately 2 mm) could be considered as the L5 segment based on the number of the fluorescent signals (above 20). L5 spinal segment could be differentiated from L4 and L6 segment based on their morphological characteristics under Cresyl violet stain. In L5-Tx group, at 2 and 4 weeks post-transection, the number of L5 spinal motoneurons was reduced by 8%. Meanwhile, Sc-Tx and Su groups showed no statistically notable changes. In this study, the authors could propose more reliable peripheral nerve axotomy model than the conventional sciatic nerve axotomy model by specifically transecting L5 spinal nerve and confining the investigating area within the L5 spinal segment.

Comparative Study of the L5 Spinal Nerve Transection Model and Sciatic Nerve Axotomy Model as a Peripheral Nerve Injury Model in Rat / 체질인류학회지

The aim of this study was to propose new more reliable peripheral nerve transection model to overcome the defect of the traditional sciatic axotomy model by specifically transecting L5 spinal nerve just after emerging from the intervertebral foramen and confining analysis area to the L5 spinal segment. The adult male Sprague-Dawley rats, weighing 300~350 g at the time of surgery, were used for the experiments. Four different experimental groups were used. 1. Sciatic nerve transection (Sc-Tx) group: transect the sciatic nerve in the popliteal fossa where it divided into the common peroneal nerve and tibial nerve. 2. L5 spinal nerve transection (L5-Tx) group: L5 spinal nerve was specifically transected. 3. Suture (Su) group: L5 spinal nerve was transected and immediately sutured. 4. Control group: the same surgical procedure with L5 spinal nerve transection group was performed except for the excision of L5 spinal nerve. To distinguish L5 motoneurons from the other level ones, the animals were received the retrograde tracer, FluoroGold into the axotomized proximal nerve stump. Serial coronal frozen sections at 40 microm thick through the L4 to L6 spinal segment was performed and the resultant total number of sections was about 180. Approximate serial 50 sections (approximately 2 mm) could be considered as the L5 segment based on the number of the fluorescent signals (above 20). L5 spinal segment could be differentiated from L4 and L6 segment based on their morphological characteristics under Cresyl violet stain. In L5-Tx group, at 2 and 4 weeks post-transection, the number of L5 spinal motoneurons was reduced by 8%. Meanwhile, Sc-Tx and Su groups showed no statistically notable changes. In this study, the authors could propose more reliable peripheral nerve axotomy model than the conventional sciatic nerve axotomy model by specifically transecting L5 spinal nerve and confining the investigating area within the L5 spinal segment.