The value of SINO robot combined with Angio Render technology-assisted stereo-electroencephalography electrode implantation for the treatment of drug-resistant epilepsy.

BACKGROUND AND OBJECTIVE: Stereo-electroencephalography (SEEG) electrodes are implanted using a variety of stereotactic technologies to treat refractory epilepsy. The value of SINO-robot for SEEG electrode implantation is rarely reported. The aim of the current study was to assess the value of SINO-robot in conjunction with Angio Render technology, in SEEG electrode implantation. We also assess its efficacy by examining factors such as localization error, operation time, and complications. METHODS: Between June 2018 and October 2020, we retrospectively reviewed 58 patients who underwent SEEG implantation to resect or ablate their epileptogenic zone (EZ) while minimizing the risk of hemorrhage. SINO-robot combined with Angio Render technology-assisted SEEG electrode implantation was used to visualize each patient' blood vessel in a 3D plane. The 3D view functionality was used to increase the safety and accuracy of the implantation, and reducing the risk of hemorrhage by avoiding said blood vessel. RESULTS: In this study, 634 SEEG electrodes were implanted in 58 patients. The mean 10.92(range 5- 18) leads per patient. The mean entry point localization error (EPLE) was 0.94 ± 0.23 mm (range: 0.39- 1.63 mm), and the mean target point localization error (TPLE) was 1.49 ± 0.37 mm (range: 0.80-2.78 mm). The mean operating time per lead (MOTPL) was 6. 18 ± 1.80 min (range: 3.02- 14.61 min). And the mean depth of electrodes was 56.96± 3.62 mm (range:27.23-124.85 mm). At a follow-up of at least one year, totally 81.57% (47/58) of patients achieved an Engel class I of seizure freedom. There were 2 patients with asymptomatic brain hematomas following SEEG placement, and no late complications or mortality in this cohort. CONCLUSIONS: SINO-robot in conjunction with Angio Render technology assist, in SEEG electrode implantation is safe and accurate in mitigating the risk of intracranial hemorrhage in patients suffering from drug-resistant epilepsy.

Diffusion spectrum imaging based semi-automatic optic radiation tractography for vision preservation in SEEG-guided radiofrequency thermocoagulation.

OBJECTIVE: To assess the efficacy and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC), using diffusion spectrum imaging (DSI) tractography to preoperatively delineate the optic radiation (OR) and reduce the risk of visual field defects (VFDs) where the epileptogenic zones (EZs) are located in or close to the eloquent visual areas. METHODS: We prospectively followed up twenty-four consecutive patients (12 males and 12 females) who underwent SEEG-guided RFTC in or near the OR pathway. A distance of ≥ 3.5 mm away from the OR on the targeted electrodes contacts that exhibited relevant ictal onset patterns, IEDs and EES during SEEG recordings, was required as our selection criterion prior to performing RFTC, enough to theoretically prevent VFDs. Using default tracking parameters, the optic radiation was tracked semi-automatically in DSI-studio. RESULTS: There were 12 male and 12 female patients ranging in age from 6 to 57 years, with follow-up period ranging from 6 to 37 months. Nineteen patients responded to RFTC (R+, 79.16 %), and 5 patients did not benefit from RFTC (R-, 20.83 %). The preoperative application of DSI semi-automatic based OR tractography was successful in the protection of the OR in all 24 patients. Three patients experienced a neurologic deficit following RFTC, and five patients had a partial quadrant visual field deficit prior to surgery that did not worsen, and none of the remaining nineteen patients had a quadrant visual field deficit. CONCLUSION: Our study validates the safety and efficacy of SEEG-RFTC as a viable therapeutic approach for epileptic foci situated in or adjacent to the visual eloquent regions. We demonstrate that DSI-based tractography offers superior precision in delineating the OR compared to DTI. We establish that implementing a criterion of a minimum distance of ≥ 3.5 mm in radius from the OR on the targeted electrode contacts prior to conducting RFTC can effectively mitigate the risk of VFDs.

Clinical features, surgical treatment, and long-term outcomes of moyamoya disease in a single institution of Fujian, Southeast China: A retrospective study.

At present, detailed demographic and clinical data of moyamoya disease (MMD) in the population of Southeast China are lacking. Therefore, this study aimed to evaluate the epidemiological and clinical features of MMD in Southeast China. Our cohort included 170 patients diagnosed with MMD over the preceding 5 years. Clinical characteristics were obtained through a retrospective chart review, while follow-up information and outcomes were obtained through clinical visits and imaging. The median age at symptom onset was 49 years (range 4-73), with a peak in the age distribution observed at 41 to 60 years. The female-to-male ratio was 1.125 (90/80), and the ratio of the ischemic type to the hemorrhagic type was 2.33 (119/50). The most common initial symptom was an ischemic event. The 5-year Kaplan-Meier risk of stroke was 4.9% for all patients treated with surgical revascularization. Of all patients, 83.9% were able to live independently with no significant disability, and 89.8% showed improved cerebral hemodynamics. Our study provided detailed demographic and clinical data on Southeastern Chinese patients with MMD, which was consistent with findings in other parts of China. Raising clinical awareness of MMD in primary hospitals is important to facilitate early diagnosis and timely treatment of MMD patients.

Cordycepin improves sensitivity to temozolomide in glioblastoma cells by down-regulating MYC.

PURPOSE: Glioblastoma is one of the malignant tumors with poor prognosis and no effective treatment is available at present. METHODS: To study the effect of cordycepin combined with temozolomide on glioblastoma, we explored the effect of the combination based on network pharmacology and biological verification. RESULTS: It was found that the drug combination significantly inhibited the cell growth, proliferation, migration and invasion of LN-229 cells. Drug combination inhibited epithelial-mesenchymal transition (EMT) by up-regulating the expression of E-cadherin and suppressing the expression of N-cadherin, Zeb1 and Twist1. Through network pharmacology, we further explored the molecular mechanism of drug combination against glioblastoma, and 36 drug-disease common targets were screened. The GO biological process analysis included 44 items (P < 0.01), which mainly involved the regulation of apoptosis, cell proliferation, cell migration, etc. The enrichment analysis of KEGG pathways included 28 pathways (P < 0.05), and the first four pathways were "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway". We detected the expression of important genes in the pathways and PPI network, and the results showed that the drug combination down-regulated NFKB1, MYC, MMP-9, MCL1, CTNNB1, and up-regulated PDCD4. CONCLUSION: Cordycepin combined with temozolomide may down-regulate MYC through "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway", which in turn regulate the expression of MCL1, CTNNB1, MMP9, PDCD4, thus regulating cell proliferation, migration and apoptosis in glioblastoma.

Diagnosis of pituitary abscess and treatment via transsphenoidal surgery: experience from 15 cases.

OBJECTIVE: Pituitary abscess is an often misdiagnosed, rare clinical disorder. To improve diagnostic accuracy and the efficacy of surgical and antibiotic therapy for patients with pituitary abscess, herein, we retrospectively reviewed 15 patients who presented with pituitary abscesses from 2005 to 2022. DESIGN: Retrospective study. PATIENTS: Fifteen patients underwent transsphenoidal surgery and received antibiotic treatment. MEASUREMENTS: Complete details regarding medical history, clinical manifestations, laboratory examinations, imaging studies, and treatment strategies were obtained for all patients. RESULTS: Most patients presented with hypopituitarism and headaches, while some presented with fever, visual disturbances, and diabetes insipidus (DI). Abscesses showed significant annular enhancement post gadolinium injection. In most patients, pituitary abscess can be cured via microscopic or endoscopic drainage of the abscess followed by antibiotic treatment. Complete cure of pituitary abscess was observed in nine patients, with six cases of prolonged hypopituitarism and only one case of recurrence. Long-term hormone replacement therapy was effective in the postoperative management of hypopituitarism. CONCLUSIONS: The typical manifestations of pituitary abscess include hypopituitarism and headaches; the presence of an enhanced ring at the edge of the mass on contrast-enhanced magnetic resonance images (MRI) is highly suggestive of pituitary abscess. We recommend antibiotic treatment for 4-6 weeks postoperatively, based on the results of bacterial cultures or metagenomic next-generation sequencing (mNGS).

Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats.

OBJECTIVE: To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats. METHODS: The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored. RESULTS: Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 ß and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01). CONCLUSIONS: Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.

GLP-1R knockdown abrogates the protective effects of liraglutide on ischaemic stroke via inhibition of M2 polarisation and activation of NLRP3 inflammasome by reducing Nrf2 activation.

Liraglutide has been recently discovered to penetrate the blood-brain barrier to exert neuroprotective effects. However, relevant mechanisms of the protective effects of liraglutide on ischaemic stroke remain to be elucidated. This study examined the mechanism of GLP-1R in regulating the protective effect of liraglutide against ischaemic stroke. Middle cerebral artery occlusion (MCAO) male Sprague-Dawley rat model with/without GLP-1R or Nrf2 knockdown was established and subjected to liraglutide treatment. Then neurological deficit and brain oedema of rats was evaluated and brain tissues were subjected to TTC, Nissl, TUNEL and immunofluorescence staining. Rat primary microglial cells firstly underwent lipopolysaccharide (LPS) treatment, then GLP-1R or Nrf2 knockdown treatment, and finally Liraglutide treatment to research the NLRP3 activation. As a result, Liraglutide protected rats' brain tissues after MCAO, which attenuated brain oedema, infarct volume, neurological deficit score, neuronal apoptosis and Iba1 expression but enhanced live neurons. However, GLP-1R knockdown abrogated these protective effects of liraglutide on MCAO rats. According to in vitro experiments, Liraglutide promoted M2 polarisation, activated Nrf2 and inhibited NLRP3 activation in LPS-induced microglial cells, but GLP-1R or Nrf2 knockdown reversed these effects of Liraglutide on LPS-induced microglial cells. Further, Nrf2 knockdown counteracted the protection of liraglutide on MCAO rats, whereas sulforaphane (agonist of Nrf2) counteracted the effect of Nrf2 knockdown on liraglutide-treated MCAO rats. Collectively, GLP-1R knockdown abrogated the protection of liraglutide on MCAO rats by activating NLRP3 via inactivating Nrf2.

Assessment of bypass patency using transcranial Doppler sonography: correlations with computerized tomography angiography findings in patients with moyamoya disease.

To explore the utility of transcranial Doppler (TCD) findings when assessing bypass patency in patients with Moyamoya disease (MMD). Computed tomography angiography (CTA) and TCD sonography (TCDS) were performed before and after surgery to evaluate bypass patency. The peak systolic flow velocity (PSV) of the superficial temporal artery (STA) and the pulsatility index (PI) were compared between the groups that achieved patency and not, and receiver operating characteristic (ROC) curve analyses were used to define the TCDS criteria revealing patency. This study included 35 hemispheres (15 women; mean age 47 years) with Moyamoya disease who underwent STA-middle carotid artery bypass in our institution between January 2022 and October 2022. The PSV first increased on postoperative days 4-5 and then decreased on postoperative days 6-7 and 7-8. Patients with transient neurological diseases (TNDs), compared to those without, evidenced a significantly lower PSV value (P < 0.05). Compared with the non-patency group, the PSV was higher (P < 0.001) in the patency group. The cutoff values reflecting patency with good sensitivity and specificity were PSV > 49.00; PSV ratio (postoperative/preoperative) > 1.218; PSV ratio (operation side/contralateral side) > 1.082; and PSV ratio (adjusted) > 1.202. In the patency group, the PSV and PI significantly increased (P < 0.001) and decreased (P < 0.001) respectively. Bypass patency can be noninvasively and accurately evaluated via TCDS, affording an objective basis for assessment of the effect of revascularization surgery on patients with MMD.

Molecular diagnosis and treatment of meningiomas: an expert consensus (2022).

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION: Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.

Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage.

OBJECTIVE: To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1ß, and IL-18 in the rat brains were detected by Western blot. RESULTS: Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1ß, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01). CONCLUSION: Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.

LncRNA CEBPA-AS1 alleviates cerebral ischemia-reperfusion injury by sponging miR-340-5p regulating APPL1/LKB1/AMPK pathway.

Long non-coding RNAs (lncRNAs) regulate neurological damage in cerebral ischemia-reperfusion injury (CIRI). This study aimed to investigate the biological roles of lncRNA CEBPA-AS1 in CIRI. Middle cerebral artery occlusion and ischemia-reperfusion injury (MCAO/IR) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) cell lines were generated; the expression of CEBPA-AS1 was evaluated by qRT-PCR. The effects of CEBPA-AS1 on cell apoptosis and nerve damage were examined. The downstream microRNA (miRNA) and mRNA of CEBPA-AS1 were predicted and verified. We found that overexpression of CEBPA-AS1 could attenuate MCAO/IR-induced nerve damage and neuronal apoptosis in the rat model. Knockdown of CEBPA-AS1 aggravated cell apoptosis and enhanced the production of LDH and MDA in the OGD/R cells. Upon examining the molecular mechanisms, we found that CEBPA-AS1 stimulated APPL1 expression by combining with miR-340-5p, thereby regulating the APPL1/LKB1/AMPK pathway. In the rescue experiments, CEBPA-AS1 overexpression was found to attenuate OGD/R-induced cell apoptosis and MCAO/IR induced nerve damage, while miR-340-5p reversed these effects of CEBPA-AS1. In conclusion, CEBPA-AS1 could decrease CIRI by sponging miR-340-5, regulating the APPL1/LKB1/AMPK pathway.

Primary central nervous system Hodgkin's lymphoma: a case report.

Primary central nervous system Hodgkin's lymphoma (CNS-HL) is extremely rare. This current case report describes a 60-year-old male patient that presented with numbness of the left lower extremity and worsening headache. After a full range of investigations and a partial resection of the right cerebellum, external ventricular drainage reservoir placement and cranioplasty, he was diagnosed with primary CNS-HL. The patient was treated with 3 g/m2 methotrexate (intravenous [i.v.], once a day, day 1) and 1 g/m2 cytarabine (i.v., every 12 h, days 2 + 3), followed by anti-programmed cell death protein 1 antibodies (200 mg sintilimab, i.v., once a day, day 1, every 3 weeks). After six courses of treatment with intrathecal injections of 50 mg cytarabine (once a day, day 1) and 5 mg dexamethasone (once a day, day 1), there was no residual lesion on cranial magnetic resonance imaging. No significant drug-related adverse events were observed. The patient has been followed up every 3 months and no relapse has occurred.

Accuracy and Feasibility Analysis of SEEG Electrode Implantation using the VarioGuide Frameless Navigation System in Patients with Drug-Resistant Epilepsy.

OBJECTIVE: The objective of the study was to evaluate the feasibility and accuracy of frameless stereoelectroencephalography (SEEG) electrode implantation in patients with drug-resistant epilepsy using the VarioGuide system. METHODS: The VarioGuide frameless navigation system was used to implant SEEG electrodes in patients with medically drug-resistant epilepsy. Demographic data, surgery duration, number of electrodes, and complications were retrospectively analyzed. Accuracy was compared by measuring the distance between the planned and actual electrode positions as determined by postoperative computed tomography images. RESULTS: A total of 141 SEEG electrodes were implanted in 19 patients from May 2015 to December 2018 with an average of 7.42 (range: 4-10) leads per patient. The average entry point localization error (EPLE) was 1.96 ± 0.47 mm (range: 0.32-3.29) and average target point localization error (TPLE) was 2.47 ± 0.79 mm (range: 0.72-4.83). The average operating time per lead (OTPL) was 14.16 ± 2.68 minutes (range: 8.64-21.58). No complications occurred. CONCLUSION: The VarioGuide frameless navigation system can be an effective method for SEEG electrode implantation in patients with drug-resistant epilepsy, particularly when the electrodes are concentrated in a relatively small region and the number of implanted electrodes is small.

GLP-1R Agonist Liraglutide Attenuates Inflammatory Reaction and Neuronal Apoptosis and Reduces Early Brain Injury After Subarachnoid Hemorrhage in Rats.

Liraglutide, one of the glucagon-like peptide 1 receptor (GLP-1R) agonists, has been demonstrated to protect brain damage produced by ischemic stroke. However, it remains unknown whether liraglutide attenuates early brain injury after subarachnoid hemorrhage. The present study was performed to explore the effect of liraglutide on early brain injury after subarachnoid hemorrhage in rats, and further investigate the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation, then received subcutaneous injection with liraglutide (50 or 100 µg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, and Evans Blue extravasation were measured 24 h after SAH. Immunofluorescent staining was performed to detect the extent of microglial activation in rat brain 24 h after SAH. TUNEL staining was performed to evaluate neuronal apoptosis in rat brain of SAH. Expression of GLP-1R, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Bcl-2, Bax, and cleaved caspase-3 in rat brain were determined by western blot. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat brain was assessed by ELISA. Neurological dysfunction, brain water content, Evans Blue extravasation, microglial activation, and neuronal apoptosis were significantly reduced by GLP-1R agonist liraglutide. Expression of GLP-1R in rat brain was decreased after SAH, which is significantly elevated by liraglutide. Expression of inflammatory mediates like COX-2, iNOS, TNF-α, and IL-1ß was increased after SAH, which were significantly inhibited by liraglutide. Furthermore, SAH caused the elevated expression of pro-apoptotic factors Bax and cleaved caspase-3 in rat brain, both of which were inhibited by liraglutide. In addition, liraglutide reversed the expression of anti-apoptotic protein Bcl-2. Our results demonstrated that liraglutide reduces early brain injury and attenuates inflammatory reaction and neuronal apoptosis in rats of SAH. Liraglutide provides neuroprotection against SAH, which might be associated with the inhibition of inflammation and apoptosis.

Baicalin Reduces Early Brain Injury after Subarachnoid Hemorrhage in Rats.

OBJECTIVE: To evaluate the effect of baicalin on subarachnoid hemorrhage (SAH) in rats and explore the potential mechanisms. METHODS: Sprague-Dawley rats underwent experimental SAH and received treatment with baicalin at 10 or 50 mg/kg after 2 and 12 h of SAH. Neurological scores, brain water content, Evans-blue extravasation, and levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), and malondialdehyde (MDA) were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), matrix metalloproteinase-9 (MMP-9), aquaporin 4 (AQP4), occludin, and zonulaoccludens-1 (ZO-1) were detected in the brain by Western blot. Heme oxygenase-1 (HO-1) was detected by quantitative polymerase chain reaction, and tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were assessed by enzyme-linked immunosorbent assay. RESULTS: Baicalin attenuated EBI 24 h after SAH in rats (P<0.05). Baicalin elevated neurological scores, GSH-Px, SOD, and increased the expression of Nrf2, NQO1, HO-1, occludin, and ZO-1 in SAH rats (P<0.05 or P<0.01). Baicalin reduced MPO, MDA, and the expression of MMP-9, AQP4, TNF-α, and IL-1ß (P<0.05 or P<0.01). CONCLUSION: Baicalin reduced SAH-induced EBI, partially via activation of the Nrf2/HO-1 pathway and inhibition of MMP-9 and AQP4.

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway.

BACKGROUND: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. MATERIALS AND METHODS: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor- kappa B (NF-κB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat brain were examined by ELISA. RESULTS: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-κB p65, COX-2, TNF-α, and IL-1ß, all of which were inhibited by LY294002. CONCLUSION: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.

LncRNA TRG-AS1 promotes glioblastoma cell proliferation by competitively binding with miR-877-5p to regulate SUZ12 expression.

Glioblastoma is one of the most fatal diseases in human central nerve system. However, the prognosis and treatment of glioblastoma still call for steady improvement. In recent years, increasing studies have revealed that the abnormal expression of long non-coding RNA (lncRNA) is closely related to carcinogenesis and prognosis. Unfortunately, many lncRNAs still need further research in their function and molecule mechanism. LncRNA TRG-AS1 hasn't been detected in any types of cancers before. TRG-AS1 is associated with poor prognosis and is upregulated in glioblastoma tissues and cells. TRG-AS1 can also accelerate glioblastoma cell proliferation in return. On the other hand, miRNA-877-5p expresses low in glioblastoma and contains binding sites with both TRG-AS1 and SUZ12. Furthermore, TRG-AS1 suppresses the expression of miR-877-5p while miR-877-5p suppresses SUZ12 expression. Overexpression of TRG-AS1 could promote the expression of SUZ12.Rescue assays demonstrates that overexpression of SUZ12 can counteract the decline of glioblastoma cell proliferation induced by knockdown of TRG-AS1. Based on all these assays, TRG-AS1 promotes glioblastoma cell proliferation by acting as a ceRNA of miR-877-5p to regulate SUZ12 expression. TRG-AS1 might serve as a new target in glioblastoma treatment.

Resveratrol downregulates the TLR4 signaling pathway to reduce brain damage in a rat model of focal cerebral ischemia.

Previous studies have demonstrated that inflammation and disruption of the blood-brain barrier (BBB) are important pathological processes during focal cerebral ischemia. Therefore, the present study evaluated the neuroprotective effects of resveratrol against brain damage, inflammation and BBB disruption in rats with focal cerebral ischemia and assessed the potential underlying molecular mechanisms. Sprague-Dawley rats underwent cerebral ischemia/reperfusion (IR) and then received intraperitoneal resveratrol (10 and 100 mg/kg) 2 h following the onset of ischemia. Following 24 h of ischemia, neurological deficit scores, cerebral infarctions, morphological characteristics, cerebral water content, myeloperoxidase (MPO) activity and Evans blue extravasation were assessed. Additionally, the protein expression levels of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB p65 were detected using western blot analyses, the mRNA expression levels of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were examined by reverse-transcription polymerase chain reaction, and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß blood levels were determined by ELISA. Resveratrol significantly reduced neurological deficit scores, cerebral infarct sizes, neuronal injury, MPO activity and EB content. Cerebral ischemia increased the expression levels of TLR4, NF-κB p65, COX-2, MMP-9, TNF-α and IL-1ß, but all of these factors were reduced by resveratrol. In conclusion, the present data suggest that resveratrol reduces inflammation, BBB disruption and brain damage in rats following focal cerebral ischemia. Additionally, the neuroprotective effects of resveratrol against cerebral ischemia may be associated with downregulation of the TLR4 pathway.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice.

BACKGROUND: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. METHODS: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. RESULTS: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] µmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. CONCLUSION: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Anticonvulsive effects of protodioscin against pilocarpine-induced epilepsy.

Epilepsy is associated with increased morbidity and mortality together and places a large financial burden on individuals and society. To evaluate the anticonvulsant action of protodioscin (PDSN) in experiments with animals with pilocarpine-induced convulsions. We assessed the activity of PDSN in pilocarpine induced seizures in combination with different agents which are acting via diverse receptors, such as atropine, memantine, nimodipine, diazepam, and flumazenil, to determine the exact receptors responsible for the action of PDSN. Furthermore, the level of antioxidant markers was investigated in the cerebellum and cerebral cortex in mice to define the antioxidant action of PDSN. The effects of PDSN on proapoptotic markers (i.e., Bcl-2, Bax, and caspase-3) was investigated via western blot analysis. PDSN significantly enhanced latency to the first convulsion and survival compared to the group treated with pilocarpine alone. Moreover, PDSN improved animal survival, and subjects experiencing no convulsions. Striatal glutamate and aspartate levels were not modified, and gamma amino butyric acid (GABA) levels increased, as a result of treatment with PDSN. The results suggest that the anticonvulsive action of PDSN is dependent on inhibitory amino acids. PDSN treatment also significantly decreased nitrite levels in the blood and brain cortex compared to the normal control. In the western blot analysis, PDSN exerted its neuroprotective effect via the upregulation of Bcl-2 and downregulation of Bax and caspase-3. The results of this study suggest that PDSN exerts neuroprotective effects via multiple mechanisms.