Glioblastoma multiforme (GBM) is the most commonly occurring brain cancer, and is characterized by its poor patient outcomes. The present study examined the mRNA expression levels of the transient receptor potential melastatin (TRPM) family in various types of cancer using the ONCOMINE database, along with their corresponding expression profiles in an array of cancer cell lines based on the Cancer Cell Line Encyclopedia (CCLE) datasets. Kaplan-Meier plotter survival analysis via the Chinese Glioma Genome Atlas (CGGA) database was also used to evaluate the prognostic value of transient receptor potential melastatin 8 (TRPM8). For the activity test on the TRPM8 channel, patch-clamp recordings and Ca 2+ measurements by fluorescence imaging of Fluo-4am were performed. Short hairpin RNA (shRNA) targeting TRPM8 was designed, synthesized and then transfected into the U251 cells via Lipofectamine 2000. The expression of extracellular singnal-regulated kinase (ERK), cyclin D1 and Bcl-2 were detected by performing western blotting and immunofluorescence. The apoptosis, proliferation and invasion of glioma cells were detected by using flow cytometry, and CCK-8 and Transwell invasion assays. In the present study, TRPM8 was distinctively upregulated in GBM cell lines. TRPM8 is functional and has the characteristic of outward rectification, which was verified via electrophysiology and Ca 2+ fluorescence imaging in U251 cells. The western blot and immunofluorescence results revealed that the expression of ERK, cyclin D1 and Bcl-2 were decreased in the shRNA interference group. The CCK-8 assay demonstrated that the proliferation ability of U251 cells in the U251/TRPM8 group was higher than that in the U251 group and U251/Con group (P<0.05). The result of the Transwell invasion assay indicated that the invasion of human glioblastoma U251 cells was positively correlated with the expression level of TRPM8. Collectively, the results of the present study indicated that Ca 2+-permeable TRPM8 nonselective cation channels contribute to survival, proliferation, apoptosis, and local tumor invasion of glioblastoma. Therefore, TRPM8 is a promising biomarker for aggressiveness of GBM, and a potential target in future anti-glioblastoma therapies.

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Aims Hyperbaric oxygen preconditioning (HBOP) attenuates brain edema, microglia activation, and inflammation after intracerebral hemorrhage (ICH). In this present study, we investigated the role of HBOP in ICH‐induced microglia polarization and the potential involved signal pathway. Methods Male Sprague‐Dawley rats were divided into three groups: SHAM, ICH, and ICH + HBOP group. Before surgery, rats in SHAM and HBOP groups received HBO for 5 days. Rats in SHAM group received needle injection, while rats in ICH and ICH + HBOP groups received 100 μL autologous blood injection into the right basal ganglia. Rats were euthanized at 24 hours after ICH, and the brains were removed for immunohistochemistry and Western blotting. Neurological deficits and brain water content were determined. Results Intracerebral hemorrhage induced brain edema, which was significantly lower in the HBOP group. The levels of MMP9 were also less in the HBOP group. HBO pretreatment resulted in less neuronal death and neurological deficits after ICH. Their immunoactivity and protein levels of M1 markers were downregulated, but the M2 markers were unchanged by HBOP. In addition, ICH‐induced pro‐inflammatory cytokine (TNF‐α and IL‐1β) levels and the phosphorylation of JNK and STAT1 were also lower in the HBOP rats. Conclusions HBO pretreatment attenuated ICH‐induced brain injuries and MMP9 upregulation, which may through the inhibiting of M1 polarization of microglia and inflammatory signal pathways after ICH.

Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV–V have high rates of disability and mortality. The objective of this study was to accurately prognosticate the outcomes of patients with poor-grade aSAH by developing a new scoring model.Methods: A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression analysis were used to devise a scoring model (total score, 0–9 points). The scores were estimated on the basis of β coefficients. A cohort of 68 patients from another institute was used to validate the model.Results: Multivariate logistic regression analysis revealed that modified Fisher grade &gt;2 [odds ratio [OR], 2.972; P = 0.034], age ≥65 years (OR, 3.534; P = 0.006), conservative treatment (OR, 5.078; P = 0.019), WFNS grade V (OR, 2.638; P = 0.029), delayed cerebral ischemia (OR, 3.170; P = 0.016), shunt-dependent hydrocephalus (OR, 3.202; P = 0.032), and cerebral herniation (OR, 7.337; P &lt; 0.001) were significant predictors for poor prognosis [modified Rankin Scale [mRS] ≥3]. A scoring system was constructed by the integration of these factors and divided the poor-grade aSAH patients into three categories: low risk (0–1 points), intermediate risk (2–3 points), and high risk (4–9 points), with predicted risks of poor prognosis of 11, 52, and 87%, respectively (P &lt; 0.001). The area under the curve in the derivation cohort was 0.844 (95% CI, 0.778–0.909). The AUC in the validation cohort was 0.831 (95% CI, 0.732–0.929).Conclusions: The new scoring model can improve prognostication and help decision-making for subsequent complementary treatment in patients with aSAH.

Glioblastoma is one of the central nervous system most aggressive and lethal cancers with poor overall survival rate. Systemic treatment of glioblastoma remains the most challenging aspect due to the low permeability of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), limiting therapeutics extravasation mainly in the core tumor as well as in its surrounding invading areas. It is now possible to overcome these barriers by using low-intensity focused ultrasound (LIFU) together with intravenously administered oscillating microbubbles (MBs). LIFU is a non-invasive technique using converging ultrasound waves which can alter the permeability of BBB/BTB to drug delivery in a specific brain/tumor region. This emerging technique has proven to be both safe and repeatable without causing injury to the brain parenchyma including neurons and other structures. Furthermore, LIFU is also approved by the FDA to treat essential tremors and Parkinson’s disease. It is currently under clinical trial in patients suffering from glioblastoma as a drug delivery strategy and liquid biopsy for glioblastoma biomarkers. The use of LIFU+MBs is a step-up in the world of drug delivery, where onco-therapeutics of different molecular sizes and weights can be delivered directly into the brain/tumor parenchyma. Initially, several potent drugs targeting glioblastoma were limited to cross the BBB/BTB; however, using LIFU+MBs, diverse therapeutics showed significantly higher uptake, improved tumor control, and overall survival among different species. Here, we highlight the therapeutic approach of LIFU+MBs mediated drug-delivery in the treatment of glioblastoma.