Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury.

Interleukin-6 (IL)-6 was originally discovered as a factor that contributes to the secondary pathological and inflammatory response in the central nervous system (CNS) following injury. However, accumulating evidence suggests that IL-6 is also involved in functional and structural recovery following CNS injury by promoting axonal sprou-ting. This suggests a potential dual role of IL-6 in CNS injury. However, the definitive function of IL-6 in neural injury and the corresponding underlying mechanisms are still topics of controversy. The present study was carried out to examine the potential function of IL-6 in resistance to neurite growth­inhibitory effects via regulation of the expression of growth associated protein-43 (GAP-43), myelin-associated neurite outgrowth inhibitor (Nogo-A) and its receptor (NgR). Rat dorsal root ganglion (DRG) neurons cultured in an inhibitory microenvironment mimicking injured CNS were used to investigate the effects of IL-6 on the outgrowth of neuronal processes. Additionally, IL-6 was subarachnoidally injected into rats to establish a spinal cord injury (SCI) model, and the neurobehavioral manifestations and neural morphology were subsequently evaluated to determine the effect of IL-6 on neural regeneration. Finally, the potential molecular mechanisms of IL-6-mediated rege-neration and functional recovery following CNS injury are discussed. The results of the present study demonstrated that the in vitro administration of IL-6 enhanced the neurite outgrowth of DRG neurons in a dose-dependent manner via resisting the inhibitory function of myelin proteins. All doses of the IL-6 subarachnoid injection improved the Basso, Beattie and Bresnahan scores following SCI, with a large number of axonal sproutings observed at the spinal lesion site, and several sprouting fibers being elongated and bypassing the lesion and entered the caudal spinal cord. Additionally, a significantly increased density area of diaminobenzidine-labeled neural fiber was observed in rats that received a subarachnoid injection of IL-6, and the rats exhibited increased expression of GAP-43 and decreased expression of Nogo-A. In conclusion, the results of the present study indicated that IL-6 interferes with the inhibitory functions of myelin proteins by upregulating the expression of GAP-43 and simultaneously downregulating the expression of Nogo-A and NgR to promote axonal sprouting and functional recovery following SCI.

Mda-9/syntenin promotes human brain glioma migration through focal adhesion kinase (FAK)-JNK and FAK-AKT signaling.

Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively. and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda- 9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.

Isolated cerebellopontine angle craniopharyngioma.

Primary cerebellopontine angle craniopharyngioma is rare; only 5 surgically treated patients have been reported. We report a 54-year-old female with craniopharyngioma occurring in isolation in the cerebellopontine angle and compare this patient with previously published reports. The origin of and surgical strategy for such tumors are discussed.

[Correlation analysis of increased blood glucose and insulin resistance after traumatic brain injury in rats].

OBJECTIVE: To study the pattern of the alterations of blood glucose, insulin and insulin sensitivity after traumatic brain injury in rats, and verify the occurrence of insulin resistance after the injury. METHODS: Based on Feeney's model of brain injury, the blood glucose and insulin concentration of the dogs measured 30 min before and at 6, 12, 24, 48, 72 and 120 h after injury. BG60-120, GIR60-120, and insulin sensitivity index (ISI) reflecting the insulin sensitivity were measured at 6, 24, 48, and 72 hours following severe traumatic brain injury using euglycemic-hyperinsulinemic clamp. RESULTS: Both the blood glucose and insulin concentration increased markedly in rats following moderate and severe brain injury. BG60-120 increased markedly, and GIR60-120 and ISI decreased significantly 6, 24, 48, and 72 h after severe brain trauma as compared with those of the sham operation group. Blood glucose concentration of rats following severe injury was positively correlated with insulin concentration and BG60-120 at the corresponding time points, but negatively with GIR60-120 and ISI. CONCLUSION: Both the blood glucose and insulin concentration increase markedly in rats following severe brain injury. Increased blood glucose even in the presence of high-level insulin is due to acute insulin resistance occurring after traumatic brain injury.

[Clinical research about brain oxygen metabolism and neuroelectrophysiology during mild hypothermia in patients with severe head injury].

OBJECTIVE: To observe the changes of brain oxygen metabolism and neuroelectrophysiology after severe brain injury, and the effects of hypothermia on severe brain injury. METHODS: 148 patients with severe brain injury (GCS 3 - 8, admitted within 10 hours from injury) were selected for this study. Patients were divided into 3 groups, Group GCS 7 - 8, Group GCS 5 - 6 and Group GCS 3 - 4. Every group were also randomly assigned to normothermia and hypothermia subgroup. Patients in the hypothermia group were cooled to 32 approximately 34 degrees C. SLSEP, BAEP, P(br)O(2) and rSaO(2) were recorded in each group at the same time. RESULTS: In the Group GCS 7 - 8, N20 in SLSEP, I/V in BAEP and rSaO(2) were improved significantly after mild hypothermia treatment, and P(br)O(2) was decreased by hypothermia; In the Group GCS 5 - 6, N20 in SLSEP, I/V in BAEP and rSaO(2) were improved by hypothermia, and P(br)O(2) was decreased in hypothermia subgroup; In the Group GCS 3 - 4, no significant difference was found. CONCLUSION: Mild hypothermia has a significant effect on patients of GCS 7 - 8 and a doubt effect on patients of GCS 5 - 6. It seem no effect on patients of GCS 3 - 4. Brain oxygen metabolism and neuroelectrophysiology are important to value the therapeutic effect on severe brain injury.