The Activation Of P38MAPK In Hypoglossal Necleus And The Effect Of NGF On Regeneration Following Hypoglossal Nerve Crush In Rat

Objective: This study was aimed to explore the activation of phospho-p38 MAP kinase (p-p38MAPK) and to evaluate the possible role of nerve growth factor (NGF) on neuronal protection and regeneration of injured nerve in a model of hypoglossal nerve injury in rats.Methods: Sixty healthy adult SD rats were used in this study. They were divided randomly into three groups (n=20 each). Surgeries were performed in two groups of the animals to crush on the left hypoglossal nerve. One group of the rats subjected to hypoglossal nerve injury were injected with NGF (mg/kg, i.p.; NGF treatment group). The other group of animals with nerve injury (NS control group) and the group with intact nerve (NC control group) were injected with same volume of normal saline in the same administration way. The rats were allowed to survive for 1,3,5,7and 14 days after operation respectively and perfused transcardially with properfixatives. Frozen sections were processed for immunohistochemstry (IHC) to decide the p-p38MAPK expression level in the motoneurons of hypoglossal nucleus. Nissl's staining was used to evaluate cellular morphological and architectural changes in the hypoglossal nucleus. Electron microscopic study was exploited to invastigate the subcellular structural alternations of the hypoglossal nerve distal to the injury site.Results: The expression level of p-p38MAPK was low in NC group and elevated in all operated animals. This increase started 1 d after the injury, the earliest time point in this study; peaked at 3 d after surgery and remained until 14 d after the operation. However, p-p38MAPK immunoreactivity in the hypoglossal motoneurons in NGF group was lower than NS control group at 5, 7, 14 d (P<0.05) after injury. The number of motoneurons in hypoglossal nucleus of injuryed side was significantly smaller than that in normal side. The survival rate of motoneurons in hypoglossal nucleus of injured side in NGF group was higher than that in NS group (P<0.05) . Ultrastructural study revealed more regenerating myelinated axons which distributed homogenously in the distal site of the lesioned hypoglossal nerve from the NGF group than NS group at 7d, 14 d. The laminal structure of myelin was clearly seen in NGF group at 14d. There were numerous proliferating Schwann cells, each with a large nucleus in NGF group. Myelinated axons lacked normal organelles and became thinly ensheathed from NS group.Conclusion: In the model of hypoglossal nerve crush in rats: 1. p-p38MAPK was slightly expression in normal hypoglossal nucleus but intensively expression after injury. 2. NGF can down-regulate p-p38MAPK expression in the motoneurons of hypoglossal nucleus after hypoglossal nerve was crushed. 3. NGF may play a protective role on neurons in rats with hypoglossal nerve injury. 4.NGF can promote the injured hypoglossal nerve regeneration and restoration .