Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

The predictive value of serum F-actin on the severity and early neurological deterioration of acute ischemic stroke: Predictive value of F-actin in stroke.

BACKGROUND: F-actin is involved in the progression of ischemic stroke and is associated with the disruption of the blood-brain barrier. In this article, we evaluated serum F-actin as a biomarker in stroke severity and early neurological deterioration (END) in acute ischemic stroke. METHODS: In this study, serum F-actin was measured in consecutively collected 140 AIS patients and 144 healthy controls matched in gender and age by ELISA. Early neurological deterioration (END) was defined as the deterioration of neurological dysfunction within 72 hours of admission, with an increase of ≥ 4 points in the NIHSS score. Severe stroke was defined as a NIHSS score>8 at admission. RESULTS: The serum F-actin level in AIS was significantly higher than healthy controls (p = 0.041). In large-artery atherosclerosis stroke and cardioembolic stroke, serum F-actin were significantly higher than that in small artery occlusion stroke (padjust = 0.019, padjust < 0.001, respectively).F-actin level above the critical value (>1.37 µg/L) was significantly associated with severe stroke (OR, 3.015; 95 %CI, 1.014-8.963; p = 0.047) . In addition, elevated level of F-actin was significantly associated with END (OR, 1.323; 95 % CI, 1.001-1.747, p = 0.049). When the level of F-actin was above the critical value (>2.17 µg/L), its association with END remained significant (OR, 6.303; 95 %CI, 2.160-18.394; p < 0.001) . CONCLUSION: F-actin is an important blood biomarker in the early stage of AIS, and high levels of F-actin are valuable in determining the severity of stroke and predicting early neurological deterioration.

Subthalamic Nucleus Deep Brain Stimulation in Primary Meige Syndrome: A 1-Year Follow-Up Study.

OBJECTIVE: To investigate the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome. MATERIALS AND METHODS: Fifteen consecutive patients who underwent STN-DBS at the Peking University People's Hospital between September 2017 and June 2018 were included in this study. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score and the BFMDRS disability score were obtained prior to surgery, and at specific time points after surgery. Patients' sleep status was also assessed before and after surgery. RESULTS: The BFMDRS movement scores decreased from 15.3 ± 4.6 to 5.2 ± 6.2 after STN-DBS, with a mean improvement of 68.6% (p < 0.05). The BFMDRS disability scores were also significantly decreased, from 6.9 ± 3.3 to 3.5 ± 2.9, with a mean improvement of 51.7% (p < 0.05). The eye, mouth, speech, and swallowing movement scores also decreased significantly after STN-DBS compared to baseline (p < 0.05). The sleep quality of the patients was also improved after surgery. CONCLUSIONS: These findings demonstrate that the STN is an effective brain target for the treatment of patients with Meige syndrome. STN-DBS was not only able to improve patients' motor symptoms, but also their sleep status.

Verbascoside suppresses the migration and invasion of human glioblastoma cells via targeting c-Met-mediated epithelial-mesenchymal transition.

Verbascoside (VB), a glycosylated phenylpropanoid compound, is derived from the plant Syringa vulgaris (Oleaceae) and has been shown to have antitumor effects in multiple human cancers, including glioblastoma (GBM); however, the underlying mechanism has not been completely elucidated. Epithelial-to-mesenchymal transition (EMT) is the pivotal event in tumor progression. c-Met, a receptor tyrosine kinase, plays an important role in GBM aggressiveness via promoting EMT. The current study aimed to explore whether VB suppresses c-Met-induced EMT and investigated the mechanism of c-Met degradation. We found that VB inhibited GBM cell growth and downregulated c-Met and the EMT markers (snail, vimentin, and zeb1) in vitro and in an orthotopic xenograft mouse model. In addition, overexpressing c-Met in glioblastoma cells abolished the effects of VB on EMT. We also used a microscale thermophoresis (MST) assay to show that VB could directly bind to the c-Met protein, and we showed that VB degraded the c-Met protein via the ubiquitination-proteasome pathway. Our study is the first to identify a new mechanism for the anticancer effects of VB, namely, the inhibition of EMT by directly targeting c-Met; the inhibition of EMT results in c-Met protein degradation through the ubiquitination-proteasome pathway. Our current research indicates that VB is a potential agent to treat GBM via the ubiquitin-mediated degradation of c-Met.

Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after MCAO in rats.

BACKGROUND AND PURPOSE: Ischemic stroke activates Toll-like receptors (TLRs), triggering rapid inflammatory cytokine production. Axl signaling has multiple roles, including regulating cytokine secretion, clearing apoptotic cells, and maintaining cell survival, however, its role in inflammation after ischemic stroke has not been examined. We hypothesized that activation of Axl by recombinant Growth-arrest-specific protein 6 (rGas6) attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after middle cerebral artery occlusion (MCAO) in rats. METH: Sprague-Dawley rats were subjected to 2h of MCAO. One hour after reperfusion, the rats were given an intranasal injection of rGas6, vehicle, or R428 (Axl receptor inhibitor). Neurological scores, infarct volumes, immunofluorescence staining, Morris Water Maze, rotarod test and histology alterations were analyzed. The expressions of proinflammatory cytokines, including IL-1ß, IL-6, TNF-α, and Gas6, Axl, STAT1, SOCS1, SOCS3 and the TLR/TRAF/NF-κB pathway were quantified using Western blot. RESULTS: Endogenous expressions of Gas6 and Axl decreased significantly by 24h after MCAO. rGas6 reduced brain infarction and improved neurologic deficits scores, and increased expression of Axl and decreased the expressions of TRAF3, TRAF6 and inflammatory factors IL-1ß, IL-6, and TNF-α. Four weeks after MCAO, rGas6 improved long-term neurological behavior and memory. Inhibition of the Axl/TLR/TRAF/NF-κB pathway reversed the brain protection by rGas6. CONCLUSION: rGas6 reduced the neurological deficits by inhibiting neuroinflammation via the TLR/TRAF/NF-κB signaling pathway. rGas6 can be used as potential treatment to ischemic stroke.

Association Between Neurodegenerative Diseases and an Increased Risk of Epilepsy Based on Single Nucleotide Polymorphisms: A Mendelian Randomization Study.

Epilepsy is a common neurological disorder characterized by transient brain dysfunction, attributed to a multitude of factors. The purpose of this study is to explore whether neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), have a causal effect on epilepsy. Mendelian randomization (MR) methods were used to analyze the causal association between neurodegenerative diseases (AD, PD, ALS, and MS) and epilepsy based on single nucleotide polymorphisms from genome-wide association studies, including inverse-variance weighted, weighted median, MR-Egger, and weighted mode methods. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept, MR-PRESSO, and heterogeneity tests. Forty-three SNPs were selected for the MR analysis of MS and epilepsy. The inverse-variance weighted method showed a significant causal association between MS and increased risk of epilepsy (odds ratio 1.046; 95% confidence interval 1.001-1.093; P = 0.043). However, AD (P = 0.986), PD (P = 0.894), and ALS (P = 0.533) were not causally associated with epilepsy. Sensitivity analysis showed that the results were robust. The MR study confirmed the causal relationship between genetically predicted MS and epilepsy but did not support the causal relationship between genetically predicted AD, PD, and ALS on epilepsy.

Alpha tocopherol treatment reduces the expression of Nogo-A and NgR in rat brain after traumatic brain injury.

BACKGROUND: Neurite outgrowth inhibitor-A (Nogo-A), myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein are three myelin-associated proteins that act as inhibitors to central nervous system regeneration. Neurite outgrowth inhibitor-A imposes the strongest effect on inhibiting axonal regeneration after traumatic brain injury. Alpha-tocopherol, a member of the vitamin E family, is recognized as an active antioxidative substance. Its use has not been well studied in brain injury research, especially in axonal regeneration research. METHODS: We obtained 99 intact adult male Sprague-Dawley rats (200-250 g) from the Experimental Animal Center of Central South University. We used the modified method of Freeney to generate moderate brain injury in the rats. We injected 600 mg/kg α-tocopherol intraperitoneally daily as traumatic brain injury (TBI) treatment. Then, we performed behavioral tests in the corresponding time point, examined brain tissues after hematoxylin-eosin staining to identify changes in cell morphology, and performed immunohistochemical staining and quantitative real-time polymerase chain reaction to detect the expression of NoGo and Nogo receptor (NgR) in brain tissue. RESULTS: For the Neurological Severity Scores of rats, there were obvious differences among the three groups at the corresponding time points. Standard hematoxylin-eosin staining showed that the brain structure of a sham-operated group of rats was clear, uniform, and compact. A TBI group exhibited hemorrhage, edema, inflammatory cell infiltration, condensed nuclei, and necrosis. We also saw glial cells and fibrous tissue proliferation. The α-tocopherol-treated TBI group had similar but less severe changes than the TBI group. Expression of Nogo-A and NgR increased after TBI compared with the sham-operated group. However, Nogo-A and NgR expression was significantly lower in the α-tocopherol-treated TBI group compared with the TBI group. Similarly, results showed that functional neurological deficits among rats in the α-tocopherol-treated TBI group were less pronounced than in the TBI group (model group). CONCLUSIONS: Our data demonstrate that α-tocopherol-treated rats had reduced microscopic evidence of brain damage. Alpha-tocopherol reduced Nogo-A and NgR expression in brain tissue after traumatic brain injury and promoted nerve regeneration. Alpha-tocopherol treatment of TBI rats had a neuroprotective role in their recovery.

Platycodin D inhibits glioblastoma cell proliferation, migration, and invasion by regulating DEPDC1B-mediated epithelial-to-mesenchymal transition.

BACKGROUND: Platycodin D (PD) is a potent bioactive constituent in the medicinal herb Platycodon grandiflorum. It has shown anticancer properties, particularly against glioblastoma (GB) and other human malignancies. DEPDC1B (DEP domain-containing protein 1B) is an oncogene associated with epithelial-mesenchymal transition (EMT). It is highly expressed in GB and correlated with tumor grade and patient prognosis. In this study, we investigated whether the antiglioma effect of PD was associated with downregulation of DEPDC1B. METHODS: Gene expression and clinical data were obtained from the China Glioma Genome Atlas and The Cancer Genome Atlas databases for glioma samples. In vitro experiments were conducted using Cell Counting Kit-8 and Transwell assays to assess the impact of PD on the proliferation, migration, and invasion of GB cells. mRNA and protein expression was evaluated using real-time polymerase chain reaction and western blotting, respectively. RESULTS: PD exerted inhibitory effects on the proliferation and motility of GB cells. PD downregulated DEPDC1B protein as well as several markers associated with EMT, namely N-cadherin, vimentin, and Snail. The suppressive effects of PD were enhanced when DEPDC1B was knocked down in GB cells, while overexpression of DEPDC1B in cells reversed the inhibitory effects of PD. CONCLUSION: PD exerts an antiglioma effect by regulating DEPDC1B-mediated EMT.

circPKD2 inhibits the glioma cell proliferation, invasion and glycolytic metabolism through regulating the miR-1278/LATS2 axis.

Glioma is the most prevalent brain tumor with a poor prognosis. Circular RNA (circ) (PKD2) has been identified as a potential tumor suppressor. However, the effect of circPKD2 on glioma has been unknown. circPKD2 expression in glioma and its potential targets were analyzed by bioinformatics methods, qRT-PCR, dual luciferase reporter, RNA-pull down and RNA immunoprecipitation assays. Overall survival was analyzed by Kaplan-Meier method. The correlation of circPKD2 expression with patient's clinical characteristics was assessed by Chi-square test. Glioma cell invasion was detected by Transwell invasion assay, and cell proliferation was determined by CCK8 and EdU assays. ATP level, Lactate production, and glucose consumption were measured by commercial assay kits, and glycolysis-related protein (Ki-67, VEGF, HK2, LDHA) levels were evaluated by western blot. circPKD2 expression was downregulated in glioma, but circPKD2 overexpression inhibited the cell proliferation, invasion, and glycolytic metabolism. Besides, patients with low circPKD2 expression had a worse prognosis. circPKD2 level was correlated with distant metastasis, WHO grade, and Karnofsky, KPS score. circPKD2 acted as a sponge of miR-1278, and LATS2 was a target gene of miR-1278. Moreover, circPKD2 could target miR-1278 to up-regulate LATS2 expression to suppress the cell proliferation, invasion, and glycolytic metabolism. These findings display that circPKD2 can function as a tumor suppressor in glioma by controlling the miR-1278/LATS2 axis and provide the potential biomarkers for glioma treatment.

Mammalian target of rapamycin signaling pathway contributes to glioma progression and patients' prognosis.

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway plays an important role in the regulation of cell growth and increasing evidence suggests its dysregulation in tumors. It also implements many other critical cellular functions, including protein degradation and angiogenesis. To date, a correlation between the mTOR pathway in human glioma and patients' prognosis has not been reported. METHODS: To address this question, we carried out an immunohistochemical study of the mTOR upstream and downstream targets phosphorylated Akt (pAkt), phosphorylated S6 ribosomal protein (pS6), and p27, as well as phosphatase and tensin homologue (PTEN) using biopsies from 96 patients with primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. RESULTS: Immunostaining revealed that the mTOR pathway was significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grade of patients with glioma. Especially, the positive expression rates of pAkt, cytoplasmic p27, and pS6 were significantly higher in patients with higher grade (P = 0.002, 0.001 and 0.002) and lower KPS score (P = 0.007, 0.005, and 0.008), which were opposite to the nuclear p27 and PENT expression. Statistical analysis showed that patients with glioma expressing pAkt, PTEN, cytoplasmic p27, nuclear p27, and pS6 have different overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.02), WHO grade (P = 0.005), pAkt (P = 0.009), PTEN (P = 0.006), cytoplasm p27 (P = 0.008), nuclear p27 (P = 0.01), and pS6 (P = 0.003) were independent prognosis factors for human glioma. CONCLUSION: These results provide convincing evidence for the first time that the mTOR pathway correlated closely with overall survival of patients with glioma and might be a novel prognostic marker.

Long-Term Retrospective Analysis of Re-do Microvascular Decompression in Patients With Hemifacial Spasm.

Objective: To explore the clinical characteristics of patients with persistent or recurrent hemifacial spasm (HFS) and the experience of microvascular decompression (MVD) in the treatment of such patients to accumulate additional clinical evidence for optimal treatment protocols. Methods: We retrospectively analyzed the clinical data, surgical methods and treatment efficacies of 176 patients with persistent or recurrent HFS from January 2009 to January 2018. Results: Missing compression zones was the main reason for symptom persistence (87.50%) or recurrence (71.50%) after MVD treatment of HFS. We divided the surgical area into three zones. Most persistent or recurrent cases had decompression only in the root exit zone (REZ) (Zone 1) but missed the ventrolateral pons-involved area (Zone 2) or the bulbopontine sulcus-involved area (Zone 3) in the first MVD. Too much use of Teflon (12.50%), arachnoid adhesions (5.60%) and Teflon granulomas (10.40%) can also cause a recurrence. The difference between preoperative and postoperative Cohen scores was statistically significant in persistent or recurrent HFS patients (p<0.05). The postoperative follow-up time ranged from 36 to 108 months (71.75 ± 22.77). Conclusions: MVD should be performed in the compression site, which is mostly located at the brainstem/facial REZ. Intraoperative exploration should be conducted in accordance with the abovementioned zones to effectively avoid missing offending vessels. Re-do MVD is effective in patients with persistent or recurrent HFS.

Relationship Between Arterial Blood Pressure During Trigeminal Nerve Combing and Surgical Outcome in Patients with Trigeminal Neuralgia.

INTRODUCTION: Changes in blood pressure during trigeminal combing have been discussed in recent years. In this study, a retrospective analysis of patients with trigeminal neuralgia (TN) requiring microvascular decompression (MVD) with nerve combing was carried out to investigate fluctuation in arterial blood pressure during trigeminal nerve combing and its surgical effect and corresponding pathogenesis. METHODS: A total of 70 cases of MVD with nerve combing performed during the treatment of primary TN patients were selected between January 2017 and January 2018 at Peking University People's Hospital. The degree of pain and prognosis of the patients were evaluated according to the visual analog scale. Postoperative facial numbness of the 2 groups were assessed by the Barrow Neurological Institute facial numbness score. Arterial blood pressure changes before and while combing the trigeminal nerve during MVD were dynamically monitored, and the patients were divided into responders and nonresponders. Total adrenaline (AD), norepinephrine (NE), and dopamine values were measured before and during trigeminal nerve combing. RESULTS: Increased arterial blood pressure during the combing of the trigeminal nerve in MVD had a significant correlation with the prognosis of patients, with patients with higher arterial blood pressure having a better prognosis (P < 0.05). In the increased arterial blood pressure patients, precombing total AD and NE means were dramatically improved (P < 0.05). CONCLUSIONS: This study shows that changes in arterial blood pressure during trigeminal nerve combing in MVD were correlated with the prognosis of patients. Further research is necessary to clarify the mechanism of increased arterial blood pressure.

Long-Term Retrospective Analysis of Microvascular Decompression in Patients With Recurrent Trigeminal Neuralgia.

Objective: To explore the clinical characteristics of patients with recurrent trigeminal neuralgia (TN) and the experience of microvascular decompression (MVD) in the treatment of such patients. Methods: We retrospectively analyzed clinical data, imaging examination results, surgical methods, and treatment efficacies in 127 patients with recurrent typical TN from January 2005 to December 2014. Results: The age of the recurrent group was higher than that of the non-recurrent group (p < 0.05). The duration of pain before the first MVD procedure was longer in the recurrent group than in the non-recurrent group (p < 0.05). Patients in the recurrent group were more likely to have compression of the trigeminal nerve by the vertebrobasilar artery (VBA) or multiple vessels than patients in the non-recurrent group (p < 0.05). A Kaplan-Meier curve showed a median pain-free survival of 12 months after the first MVD procedure. The severity of pain (preoperative visual analog scale [VAS] score) in patients with recurrence was lower than that in patients with first-onset TN (p < 0.05). Vessel compression, Teflon compression or granuloma and arachnoid adhesion were considered the main causes of recurrence. Postoperative Barrow Neurological Institute (BNI) scores in the redo MVD group were excellent (T = 2) for 69 patients (53.33%) and good (T = 3) for 46 patients (36.22%). The postoperative follow-up was 63-167 months (105.92 ± 25.66). During the follow-up, no recurrence was noted. All complications were cured or improved. Conclusions: Microvascular decompression (MVD) is an effective surgical method for the treatment of TN. For recurrent patients, reoperation can achieve good results.

Astrogliosis inhibition attenuates hydrocephalus by increasing cerebrospinal fluid reabsorption through the glymphatic system after germinal matrix hemorrhage.

Germinal matrix hemorrhage (GMH) results from the rupture of the immature thin-walled blood vessels and consequent bleeding into the subependymal germinal matrix and possible lateral ventricles. The purpose of this study is to investigate how astrogliosis impacts the glymphatic-meningeal lymphatic system in cerebrospinal fluid (CSF) reabsorption after GMH and how the anti-scarring agent olomoucine attenuates post-hemorrhagic hydrocephalus. GMH was induced by stereotaxic collagenase infusion into P7 Sprague-Dawley rats of both sexes. Western blot and immunofluorescence were used to assess astrogliosis and how astrogliosis affects glymphatic function by measuring Aquaporin-4 expression. Intracisternal injection of fluorescence tracer was used to measure CSF diffusion throughout the brain, its dispersion in the paravascular area and CSF drainage into the deep cervical lymph nodes at 28 days after GMH. Both short-term and long-term behavioral tests were used to assess the neurological outcomes. Nissl staining was used to assess the morphological changes at 28 days after hemorrhage. GMH elicited astrogliotic scarring and reduced the exchange between CSF and interstitial fluid, as well as CSF reabsorption through the meningeal lymphatic vessels. This might be associated with redistribution of Aquaporin-4. Olomoucine ameliorated scar tissue formation and attenuated post-hemorrhagic hydrocephalus. These findings of this study suggested that the glymphatic system might play a role in CSF reabsorption in neonates following GMH. Scar tissue formation impairs this CSF clearance route, and therefore astrogliosis inhibition might be a potential therapeutic strategy for neonatal post-hemorrhagic hydrocephalus.

Prospective Study of Neuroendoscopy versus Microscopy: 213 Cases of Microvascular Decompression for Trigeminal Neuralgia Performed by One Neurosurgeon.

OBJECTIVE: To compare the efficacy and complications of microvascular decompression (MVD) by complete neuroendoscopy versus microscopy for 213 cases of trigeminal neuralgia (TN). METHODS: Between January 2014 and January 2016, 213 patients with TN were randomly assigned to the neuroendoscopy (n = 105) or microscopy (n = 114) group for MVD via the suboccipital retrosigmoid approach. All procedures were performed by the same neurosurgeon. Follow-up was conducted by telephone interview. Statistical data were analyzed with the chi-square test, and a probability (P) value of ≤0.05 was considered statistically significant. Chi-square test was conducted using SAS 9.4 software (SAS Institute, Cary, North Carolina, USA). RESULTS: There were no statistical differences between the 2 groups in pain-free condition immediately post procedure, pain-free condition 1 year post procedure, hearing loss, facial hypoesthesia, transient ataxia, aseptic meningitis, intracranial infections, and herpetic lesions of the lips. There were no instances of death, facial paralysis, cerebral hemorrhage, or cerebrospinal fluid leakage in either group. CONCLUSIONS: There were no significant differences in the cure rates or incidences of surgical complications between neuroendoscopic and microscopic MVD.

Observation of Effects of Different Surgical Treatments on Unilateral Masticatory Muscle Spasm.

BACKGROUND: Unilateral masticatory muscle spasm is a rare disease without a generally accepted and efficacious treatment plan. OBJECTIVE: We sought to compare the effects of different surgical treatments on unilateral masticatory muscle spasm. METHODS: A retrospective analysis of the surgical treatment and effects of 10 cases of unilateral masticatory muscle spasm occurred between February 2010 and September 2016. Three cases underwent complete amputation of the trigeminal motor branch, 3 cases underwent partial amputation of the trigeminal motor branch, and 4 cases received only vascular decompression. All patients were followed up by telephone interview after surgery. RESULTS: In the simple vascular decompression group, 3 cases were cured and 1 was cured after a delay. Of these 3 cases, 1 case became aggravated 2 years after the operation, 1 case became aggravated 5 years after the operation, and 1 case showed no change during the follow-up period. In the partial amputation group, 2 cases were cured and 1 case was alleviated. Of the 2 patients who were cured, 1 suffered recurrence 2 years later, while the other case showed no recurrence during the follow-up period. In the complete amputation group, 1 case was cured with a delay and 2 cases were cured immediately with no recurrence during the follow-up. Mild atrophy of the temporal muscle occurred gradually with no restriction of the mouth opening in 2 cases. CONCLUSIONS: Complete amputation of the trigeminal nerve did achieve better effects than pure microvascular decompression and partial amputation of the trigeminal motor branch, but it may lead to mild temporal muscle atrophy.

A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats.

Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

Safety and feasibility of low-dose fluorescein-guided resection of glioblastoma.

OBJECTIVES: The extent of resection is an independent predictor of prognosis in patients with glioblastomas. Although fluorescein sodium may enhance intraoperative visualization of tumor margin and increase the extent of glioblastoma, the dose related anaphylactic reaction is still a major concern. In the present study, we used allergy skin testing to exclude the patients susceptible to anaphylaxis preoperatively, and then investigated the feasibility of low-dose fluorescein sodium to guide glioblastoma resection intraoperatively, thereby to improve the safety of fluorescein-guided glioma resection. PATIENTS AND METHODS: Patients with suspected glioblastoma based on brain MRI were subjected to allergy skin intradermal tests for fluorescein sodium preoperatively. Only those with negative allergy skin tests received intravenous injection of low dose fluorescein sodium (1-2 mg/kg) during microsurgical tumor resection under dedicated Yellow 560 filter. The degree of fluorescent staining was documented and the extent of resection was evaluated by MRI scan. RESULTS: One patient with positive allergy skin test was excluded from fluorescein sodium administration and no anaphylactic reaction was found during fluorescein sodium guided surgery in the patients who were negative for allergy skin tests. The low dose fluorescein sodium (1-2 mg/kg) could provide enough visualization of tumors with sufficient discrimination from surrounding normal brain tissue and improve the resection extent of glioblastoma. CONCLUSION: Preoperative allergy skin test is a useful method to exclude the patients susceptible to anaphylaxis, together with intraoperative low dose fluorescein sodium administration, may facilitate glioblastoma resection by fluorescence guidance while avoid safety concern of dose-related anaphylaxis.

Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats.

BACKGROUND: Germinal matrix hemorrhage (GMH) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (PHH) is a common complication of GMH. A sodium-coupled bicarbonate exchanger (NCBE) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of PHH. Following GMH, iron degraded from hemoglobin has been linked to PHH. Choroid plexus epithelial cells also contain iron-responsive element-binding proteins (IRPs), IRP1, and IRP2 that bind to mRNA iron-responsive elements. The present study aims to resolve the following issues: (1) whether the expression of NCBE is regulated by IRPs; (2) whether NCBE regulates the formation of GMH-induced hydrocephalus; and (3) whether inhibition of NCBE reduces PHH development. METHODS AND RESULTS: GMH model was established in P7 rat pups by injecting bacterial collagenase into the right ganglionic eminence. Another group received iron trichloride injections instead of collagenase. Deferoxamine was administered intraperitoneally for 3 consecutive days after GMH/iron trichloride. Solute carrier family 4 member 10 small interfering RNA or scrambled small interfering RNA was administered by intracerebroventricular injection 24 hours before GMH and followed with an injection every 7 days over 21 days. NCBE expression increased while IRP2 expression decreased after GMH/iron trichloride. Deferoxamine ameliorated both the GMH-induced and iron trichloride-induced decrease of IRP2 and decreased NCBE expressions. Deferoxamine and solute carrier family 4 member 10 small interfering RNA improved cognitive and motor functions at 21 to 28 days post GMH and reduced cerebrospinal fluid production as well as the degree of hydrocephalus at 28 days after GMH. CONCLUSIONS: Targeting iron-induced overexpression of NCBE may be a translatable therapeutic strategy for the treatment of PHH following GMH.

Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion.

Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats. Male SD rats were subjected to pMCAO or sham surgery. Delayed recanalization was performed on either day 3, 7, or 14 after pMCAO in a subset of animals. Cerebral blood flow was monitored during suture insertion, during recanalization, and then at sacrifice. Neurological function was evaluated for 1 week after delayed recanalization and at 4 weeks post-ictus. After sacrifice, cerebral morphology was measured. Compared to no treatment, delayed recanalization restored cerebral blood flow, leading to sensorimotor recovery, improved learning and memory, reduced infarct volume, and increased neural stem/progenitor cells within the infarction. The data indicate that earlier delayed recanalization leads to better functional and histological recovery. Yet, even restoring cerebral blood flow 14 days after pMCAO allows for rats to regain sensorimotor function. This exploratory study suggests that delayed recanalization may be a viable option for treatment of permanent large vessel stroke.