Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6.

BACKGROUND: Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear. METHODS: Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model. RESULTS: In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection. CONCLUSION: In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. Video Abstract.

Clinical use of a neuronavigation system in hemangioblastoma resection of posterior cranial fossa.

The aim of this study was to retrospectively evaluate the effectiveness of the Stryker Leibinger neuronavigation system in surgical resection of hemangioblastomas of the posterior fossa. The study included 16 cases of solid hemangioblastoma of posterior cranial fossa treated since we began using Stryker Leibinger neuronavigation system-assisted microneurosurgery in 2003. These cases were compared on the basis of time, blood loss, and complications to 19 similar cases of solid hemangioblastoma that underwent conventional microneurosurgical resection prior to 2003. All patients in the experimental (neuronavigation-assisted) group underwent surgical resection without complications while the control groups' resections all involved blood loss related to the longer operation time. Neuronavigation also resulted in a clear field of surgical vision and clear lesion boundaries, making it easier to remove lesions and reduce accidental injury of adjacent normal structures. The application of navigation technology is very valuable for solid hemangioblastoma operations not only by shortening operative time, thereby significantly reducing operative blood loss, but also by making surgical excision easier, reducing damage to adjacent normal structures, and decreasing surgical complications and mortality.

Efficacy of subdural saline injection during surgery for acute epidural haematomas.

PRIMARY OBJECTIVE: The purpose of this study was to investigate the efficacy of subdural space saline injection surgery in the management of large acute epidural haematomas (EDHs). METHODS AND PROCEDURES: Over a period of 6 years, the authors employed the technique of subdural space saline injection to facilitate elevation of dura after evacuation of supratentorial epidural haematomas. MAIN OUTCOMES AND RESULTS. Eighty patients with supratentorial epidural haematomas underwent the procedure. Infusion of saline in the subdural space not only helps elevation of the dura, facilitate haemostasis and application of suspension stitches during operation, it also avoids ICP fluctuations during the operations. Post-operative CT scans showed rapid disappearance of saline and reposition of cerebral structure. No patient required re-operation for residual haematoma. CONCLUSIONS: Subdural saline injection is an effective operative technique in the management of large epidural haematoma.