Previous studies have shown beneficial effects of mesenchymal stem cell (MSC) transplantation in central nervous system (CNS) injuries, including traumatic brain injury (TBI). Potential repair mechanisms involve transdifferentiation to replace damaged neural cells and production of growth factors by MSCs. However, few studies have simultaneously focused on the effects of MSCs on immune cells and inflammation-associated cytokines in CNS injury, especially in an experimental TBI model. In this study, we investigated the anti-inflammatory and immunomodulatory properties of MSCs in TBI-induced neuroinflammation by systemic transplantation of MSCs into a rat TBI model. MSCs were transplanted intravenously into rats 2 h after TBI. Modified neurologic severity score (mNSS) tests were performed to measure behavioral outcomes. The effect of MSC treatment on neuroinflammation was analyzed by immunohistochemical analysis of astrocytes, microglia/macrophages, neutrophils and T lymphocytes and by measuring cytokine levels [interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, interferon-γ, RANTES, macrophage chemotactic protein-1, macrophage inflammatory protein 2 and transforming growth factor-β1] in brain homogenates. The immunosuppression-related factors TNF-α stimulated gene/protein 6 (TSG-6) and nuclear factor-κB (NF-κB) were examined by reverse transcription-polymerase chain reaction and Western blotting. Intravenous MSC transplantation after TBI was associated with a lower density of microglia/macrophages and peripheral infiltrating leukocytes at the injury site, reduced levels of proinflammatory cytokines and increased anti-inflammatory cytokines, possibly mediated by enhanced expression of TSG-6, which may suppress activation of the NF-κB signaling pathway. The results of this study suggest that MSCs have the ability to modulate inflammation-associated immune cells and cytokines in TBI-induced cerebral inflammatory responses. This study thus offers a new insight into the mechanisms responsible for the immunomodulatory effect of MSC transplantation, with implications for functional neurological recovery after TBI.

Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through the release of a variety of bioactive molecules, thereby protecting the central nervous system. Previously, we reported that MSCs have the ability to modulate inflammatory responses in a traumatic brain injury model and that the potential mechanisms may be partially attributed to upregulated TNF-α stimulated gene/protein 6 (TSG-6) expression. However, whether TSG-6 exerts an anti-inflammatory effect by affecting microglia is not fully understood. In this study, we investigated the anti-inflammatory effects of MSCs and TSG-6 in an in vitro lipopolysaccharide (LPS)-induced BV2 microglial activation model. We found that MSCs and TSG-6 significantly inhibited the expression of pro-inflammatory mediators in activated microglia. However, MSC effects on microglia were attenuated when TSG-6 expression was silenced. In addition, we found that the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways in LPS-stimulated BV2 microglial cells was significantly inhibited by TSG-6. Furthermore, we found that the presence of CD44 in BV2 microglial cells was essential for MSC- and TSG-6-mediated inhibition of pro-inflammatory gene expression and of NF-κB and MAPK activation in BV2 microglial cells. The results of this study suggest that MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia. Our study indicates that novel mechanisms are responsible for the immunomodulatory effect of MSCs on microglia and that MSCs, as well as TSG-6, might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with microglial activation.

Type 2 trigeminal neuralgia (TN) is an intractable neuropathic pain syndrome compared with type 1 TN because of the difficulty of diagnosis as well as the unsatisfactory prognosis. Neurovascular compression (NVC) is considered the major pathology of TN. Routine magnetic resonance imaging (MRI) sequences are inadequate for revealing the effect of NVC which is related to the surgical decision and outcome. The decreasing of fractional anisotropy (FA), one of the MRI diffusion tensor imaging (DTI) metrics, is correlated with the demyelination of trigeminal nerve (TGN) that reveal the severity of NVC. A retrospective review of patients treated with micro-vascular decompression (MVD) surgery was undertaken. All the patients were diagnosed as type 2 TN. FA of TGN of both sides were measured. The FA declining proportion = ((the mean FA value of healthy lateral)-(the mean FA value of the symptomatic lateral))/(the mean FA value of healthy lateral). Declining proportion of FA value, discovery of surgery and outcome of MVD were recorded and analyzed. Logistic regression analysis and linear regression analysis were employed to analyze the risk factors of declining proportion of FA value and MVD outcome. Nineteen patients were assessed in our study. The average declining proportion of FA value for all patients was 0.25 ± 0.12. The average declining proportion of FA value of “success” and “failure” group was 0.32 ± 0.09 to 0.14 ± 0.10 (P = 0.002 < 0.05). The declining proportion of FA value of artery (including the artery plus vein situation) was 0.34 ± 0.06 in contrast to 0.15 ± 0.08 of vein (P = 0.000 < 0.05). MVD outcome was correlated with declining proportion of FA value (AUC = 0.900). Furthermore, declining proportion of FA value was higher in arterial compression situation. FA value quantitatively showed the alteration of TGN caused by NVC. It provided direct evidence about the effect of NVC which facilitated the diagnosis and surgical decision of type 2 TN. Besides, significant reduction of FA value may predict an optimistic outcome of MVD.

Background: Glioma is one of the most common malignant tumors of the central nervous system. Immune infiltration of tumor microenvironment was associated with overall survival in low grade glioma (LGG). However, effects of Tyrosine phosphatase receptor type N (PTPRN) on the progress of LGG and its correlation with tumor infiltration are unclear. Methods: Here, datasets of LGG were from The Cancer Genome Atlas (TCGA) and normal samples were from GTEx dataset. Gepia website and Human Protein Atlas (HPA) Database were used to analyze the mRNA and protein expression of PTPRN. We evaluated the influence of PTPRN on survival of LGG patients. MethSurv was used to explore the expression and prognostic patterns of single CpG methylation of PTPRN gene in LGG. The correlations between the clinical information and PTPRN expression were analyzed using logistic regression and Multivariate Cox regression. We also explored the correlation between PTPRN expression and cancer immune infiltration by TIMER. Gene set enrichment analysis (GSEA) was formed using TCGA RNA-seq datasets. Results: PTPRN mRNA and protein expression decreased in LGG compared to normal brain tissue in TCGA and HPA database. Kaplan-Meier analysis showed that the high expression level of PTPRN correlated with a good overall survival (OS) of patients with LGG. The Multivariate Cox analysis demonstrated that PTPRN expression and other clinical-pathological factors (age, WHO grade, IDH status, and primary therapy outcome) significantly correlated with OS of LGG patients. The DNA methylation pattern of PTPRN with significant prognostic value were confirmed, including cg00672332, cg06971096, cg01382864, cg03970036, cg10140638, cg16166796, cg03545227, and cg25569248. Interestingly, PTPRN expression level significantly negatively correlated with infiltrating level of B cell, CD4+ T cells, Macrophages, Neutrophils, and DCs in LGG. Finally, GSEA showed that signaling pathways, mainly associated with tumor microenvironment and immune cells, were significantly enriched in PTPRN high expression. Conclusion: PTPRN is a potential biomarker and correlates with tumor immune infiltration in LGG.

Background: Evidence regarding the relationship between preoperative platelet and 30-day postoperative mortality of intracranial tumor patients undergoing craniotomy is still limited. Therefore, the present research was conducted to explore the link of the platelet and 30-day postoperative mortality. Methods: Electronic medical records of 18,642 adult patients undergoing craniotomy for brain tumors from 2012 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program, were subject to secondary retrospective analysis. A binary logistic regression model evaluated the independent association between preoperative platelet and 30-day postoperative mortality. A generalized additive model and smooth curve fitting was conducted to explore the exact shape of the curve between them. Additionally, We also conducted sensitivity analyses to test the robustness of the results, and performed subgroup analyses. Results: Eighteen thousand sixty-three patients were included in this study analysis. Of these, 47.49% were male. The mean preoperative platelet value was (244.12 ± 76.77) × 10⁹/L. The 30-day postoperative mortality of included participants was 2.5% (452/18,063). After adjusting covariates, the results showed that preoperative platelet was positively associated with 30-day postoperative mortality (OR = 0.999, 95%CI: 0.997, 1.000). There was also a nonlinear relationship between preoperative platelet and 30-day postoperative mortality, and the inflection point of the platelet was 236. The effect sizes (OR) on the right and left sides of the inflection point were 1.002 (1.000, 1.004) and 0.993 (0.990, 0.995), respectively. And sensitive analysis demonstrated the robustness of the results. Subgroup analysis showed a stronger association between preoperative platelet and 30-day postoperative mortality in non-emergency surgery patients when preoperative platelet value is less than 235 × 10⁹/L. Conclusions: This research demonstrates a positive and non-linear relationship between preoperative platelet and 30-day postoperative mortality in U.S. adult brain tumor patients undergoing craniotomy. Preoperative platelet is strongly related to 30-day postoperative mortality when the platelet is less than 235 × 10⁹/L. Proper preoperative management of platelet and maintenance of platelet near inflection point (235) could reduce risk of 30-day postoperative mortality in these cases.

Central nervous system (CNS) tuberculoma is a rare disease with severe neurological deficits. This retrospective research is to review the data of patients diagnosed as CNS tuberculoma. Surgeries were performed in all patients. The clinical features especially the neurological image and the anatomical characters of the tuberculomas were concerned. Totally 11 patients diagnosed as CNS tuberculoma were admitted in Guangzhou First People’s Hospital (7cases) and Changzheng Hospital (4 cases) during 2006–2015. The data including preoperative condition, neurological imaging, and surgical findings was collected and analyzed. The lesions of nine patients (9/11) were totally or subtotally excised and two (2/11) were partially excised. Neurological functions of all patients were improved after surgery without secondary infection. Lesions of nine (9/11) patients preoperatively progressed as a result of paradoxical reaction. Of the 9 patients demonstrated paradoxical progression, all lesions were partially or totally located at the cisterns or the subarachnoid space. Preoperative ATTs lasted 2 to 12 months and tuberculomas were not eliminated. The arachnoid was found thickened and tightly adhered to the lesions during surgeries. Of the 2 cases that paradoxical reaction were excluded, both patients (case 6, intramedullary tuberculoma; case 11, intradural extramedullary tuberculoma) were admitted at onset of the disease. ATTs were preoperatively given for 1 week as neurological deficits aggravated. The tuberculous lesions of CNS or other system showed no obvious change and paradoxical reaction could not be established in both cases. Exudates of tuberculosis is usually accumulated in the cisterns and frequently results in the paradoxical formation of tuberculoma. Intracisternal tuberculoma is closely related to paradoxical reaction and refractory to anti-tuberculosis therapy. Micro-surgical excision is safe and effective. Early surgical intervention may be considered in the diagnosis of intracisternal tuberculoma especially when paradoxical reaction participates in the development of tuberculoma.