IFN-γ-STAT1-mediated CD8+ T-cell-neural stem cell cross talk controls astrogliogenesis after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) causes nearly all patients to suffer from protracted disabilities. An emerging therapeutic strategy involving the recruitment of endogenous neural stem cells (NSCs) has been developed. However, endogenous NSCs in the adult spinal cord differentiate into mostly astrocytes after traumatic injury, forming glial scars, which is a major cause of regeneration failure in SCI. Thus, understanding which factors drive the activation and differentiation of endogenous NSCs after SCI is critical for developing therapeutic drugs. METHODS: The infiltration, state, and location of CD8+ T cells in spinal cord after traumatic injury were analyzed by flow cytometry and immunofluorescence (IF) staining. The Basso Mouse Scale (BMS) scores and rotarod testing were used for motor behavioral analysis. NSCs were co-cultured with CD8+ T cells. EdU assay was used to detect proliferative cells. Western blotting was used to analyze the expression levels of STAT1, p-STAT1, and p27. ChIP-seq and ChIP-qRT-PCR analyses were used to detect the downstream of STAT1. Nestin-CreERT2::Ai9 transgenic mice were used to genetic lineage tracing of Nestin+ NSCs after SCI in vivo. RESULTS: A prolonged increase of activated CD8+ T cells occurs in the injured spinal cords. The behavioral analysis demonstrated that the administration of an anti-CD8 antibody promotes the recovery of locomotor function. Then, we discovered that CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1 pathway in vitro. ChIP-seq and ChIP-qRT-PCR analysis revealed that STAT1 could directly bind to the promoters of astrocyte marker genes GFAP and Aldh1l1. Genetic lineage tracing of Nestin+ NSCs demonstrated that most NSCs differentiated into astrocytes following SCI. Depleting CD8+ T cells reduced the differentiation of NSCs into astrocytes and instead promoted the differentiation of NSCs into oligodendrocytes. CONCLUSION: In conclusion, CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1-GFAP/Aldhl1l axis. Our study identifies INF-γ as a critical mediator of CD8+ T-cell-NSC cross talk and a potential node for therapeutic intervention in SCI.

Design and validation of a new scale for prehospital evaluation of stroke and large vessel occlusion.

Background: Rapid recognition of acute stroke and large vessel occlusion (LVO) is essential in prehospital triage for timely reperfusion treatment. Objective: This study aimed to develop and validate a new screening tool for both stroke and LVO in an urban Chinese population. Methods: This study included patients with suspected stroke who were transferred to our hospital by emergency medical services between July 2017 and June 2021. The population was randomly partitioned into training (70%) and validation (30%) groups. The Staring-Hypertension-atrIal fibrillation-sPeech-weakneSs (SHIPS) scale, consisting of both clinical and medical history information, was generated based on multivariate logistic models. The predictive ability of the SHIPS scale was evaluated and compared with other scales using receiver operating characteristic (ROC) curve comparison analysis. Results: A total of 400 patients were included in this analysis. In the training group (n = 280), the SHIPS scale showed a sensitivity of 90.4% and specificity of 60.8% in predicting stroke and a sensitivity of 75% and specificity of 61.5% in predicting LVO. In the validation group (n = 120), the SHIPS scale was not inferior to Stroke 1-2-0 (p = 0.301) in predicting stroke and was significantly better than the Cincinnati Stroke Triage Assessment Tool (C-STAT; formerly CPSSS) and the Prehospital Acute Stroke Severity scale (PASS) (all p < 0.05) in predicting LVO. In addition, including medical history in the scale was significantly better than using symptoms alone in detecting stroke (training group, 0.853 versus 0.818; validation group, 0.814 versus 0.764) and LVO (training group, 0.748 versus 0.722; validation group, 0.825 versus 0.778). Conclusion: The SHIPS scale may serve as a superior screening tool for stroke and LVO identification in prehospital triage. Including medical history in the SHIPS scale improves the predictive value compared with clinical symptoms alone.

Prognostic Factors and Treatments Efficacy in Spontaneous Spinal Epidural Hematoma: A Multicenter Retrospective Study.

BACKGROUND AND OBJECTIVES: Spontaneous spinal epidural hematoma (SSEH) is an uncommon but serious condition with a high morbidity rate. Although SSEH is related to numerous risk factors, its etiology remains unclear. There is a paucity of data on its prognostic factors. We aim to evaluate prognostic factors for SSEH in this study. METHOD: A retrospective study was performed on patients who were admitted for SSEH in 3 academic neurosurgical centers from January 2010 to June 2021. Clinical parameters, including clinical condition on admission, anticoagulants use, imaging modality, the timing and type of surgery performed, and outcomes, were collected. Prognostic factors were analyzed. The Frankel scale was used to assess the clinical condition. RESULTS: A total of 105 patients with SSEH were retrieved from medical records, with a mean age of 51.3 years. Eighty-three patients (79%) complained of acute onset of severe neck or back pain. Eighty-two patients (78%) suffered from moderate to severe neurologic deficits (Frankel scale A-C). Anticoagulation usage was found in 20% of cases. Lower thoracic spine (p = 0.046), use of anticoagulants (p = 0.019), sphincter function disfunction (p = 0.008), severe neurologic deficits at admission (p < 0.001), and rapid deterioration (<1 hour, p = 0.004) were found to be associated with poor outcomes. Surgical decompression was performed in 74 (70%) cases. The univariate and multivariate analysis revealed that preoperative severe neurologic deficits (p = 0.005) and extended paraplegia time (>12 hours, p = 0.004) were independent adverse prognostic factors. The univariate analysis revealed that lower thoracic spine location (p = 0.08) and rapid progression (<6 hours, p = 0.005) were correlated with poor prognosis, but the multivariate analysis failed to identify them as independent prognostic factors. DISCUSSION: Adverse prognostic factors for SSEH might include thoracic segment location, use of anticoagulation, severe neurologic deficits on admission, sphincter dysfunction, and rapid progression. Preoperative neurologic deficit and extended paraplegia time were strongly correlated with the prognosis in the subset of patients who underwent surgical decompression. Timely surgical decompression is recommended for patients with moderate/severe neurologic deficits or progressive neurologic deterioration.

Combinatorial therapeutic strategies for enhanced delivery of therapeutics to brain cancer cells through nanocarriers: current trends and future perspectives.

Brain cancer is the most aggressive one among various cancers. It has a drastic impact on people's lives because of the failure in treatment efficacy of the currently employed strategies. Various strategies used to relieve pain in brain cancer patients and to prolong survival time include radiotherapy, chemotherapy, and surgery. Nevertheless, several inevitable limitations are accompanied by such treatments due to unsatisfactory curative effects. Generally, the treatment of cancers is very challenging due to many reasons including drugs' intrinsic factors and physiological barriers. Blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) are the two additional hurdles in the way of therapeutic agents to brain tumors delivery. Combinatorial and targeted therapies specifically in cancer show a very promising role where nanocarriers' based formulations are designed primarily to achieve tumor-specific drug release. A dual-targeting strategy is a versatile way of chemotherapeutics delivery to brain tumors that gets the aid of combined ligands and mediators that cross the BBB and reaches the target site efficiently. In contrast to single targeting where one receptor or mediator is targeted, the dual-targeting strategy is expected to produce a multiple-fold increase in therapeutic efficacy for cancer therapy, especially in brain tumors. In a nutshell, a dual-targeting strategy for brain tumors enhances the delivery efficiency of chemotherapeutic agents via penetration across the blood-brain barrier and enhances the targeting of tumor cells. This review article highlights the ongoing status of the brain tumor therapy enhanced by nanoparticle based delivery with the aid of dual-targeting strategies. The future perspectives in this regard have also been highlighted.

Ventriculoperitoneal Shunt Alone for Cerebrospinal Fluid Rhinorrhea With Neuroendocrine Alterations in Idiopathic Intracranial Hypertension: A Case Report and Literature Review.

Spontaneous skull base cerebrospinal fluid (CSF) leaks due to idiopathic intracranial hypertension (IIH) are a rare entity. Patients often present with CSF rhinorrhea, recurrent meningitis, chronic headache, and visual defects, while few patients have been reported to present with neuroendocrine alterations. Endonasal endoscopic repair is the first-line treatment for these leaks at present. However, the relatively high risk of recurrence remains the main cause of reoperation because of elevated intracranial pressure (ICP) after endoscopic surgery and absence of postoperative ICP management. A shunting procedure may stop CSF leakage or relieve symptoms in complex cases, and this is presently well-known as the last-line therapy for CSF liquorrhea. We describe a 29-year-old woman with spontaneous CSF rhinorrhea and neuroendocrine alterations due to IIH, and with no previous history of trauma, tumor, or nasal surgery. The bone defect in the skull base became implicated when the site of the leak was detected by cranial magnetic resonance imaging and computed tomography (CT). The patient was successfully managed via ventriculoperitoneal shunt (VPS) alone without endoscopic repair, and neuroendocrine alterations resolved after the shunting procedure.

Severe contralateral carotid stenosis or occlusion drive 30-day risk after carotid endarterectomy.

OBJECTIVES: The significant effects on the treatment of severe carotid stenosis by carotid endarterectomy have been widely recognized. However, it is controversial whether patients with severe contralateral carotid stenosis or occlusion (SCSO) can benefit from carotid endarterectomy surgery. This study aimed to estimate the SCSO effects on early outcomes after carotid endarterectomy with selective shunting. METHODS: Between August 2011 and October 2019, a total of 617 patients who underwent carotid endarterectomy with selective shunting were analyzed. SCSO was defined as >70% luminal narrowing of the contralateral extracranial carotid stenosis or occlusion. Of these patients, 116 were categorized into an SCSO group while the rest were assigned to the non-SCSO group. Primary study outcomes were the occurrence of major adverse events, defined as stroke, all-cause mortality, and myocardial infarction during the perioperative period after carotid endarterectomy. Traditional multivariable logistic regression model and logistic regression model adjusted for propensity scores were used to estimate the SCSO effects on primary outcomes. Interaction and stratified analyses were conducted according to age, sex, comorbidities (hypertension, diabetes), preoperative neurological deficit, preoperative symptoms, and shunt use. RESULTS: Mean age was 68.5 ± 9.2 years (86.1% men). Overall major adverse events rate within 30 days was 2.5%. Major adverse events rates in SCSO and non-SCSO groups were 9.5% and 1.6%, respectively. This difference was statistically significant (p < 0.001). In multivariable regression analysis, patients with SCSO had a higher risk of major adverse events (non-SCSO vs. SCSO: aOR 5.05 [95% CI, 1.78-14.55]). In 342 propensity score matched patients, results were consistent (propensity score: aOR, 3.78 [95% CI, 1.13-12.64]). CONCLUSIONS: SCSO is an independent predictor of 30-day major adverse events. Whether these patients with SCSO are suitable for carotid endarterectomy should be carefully considered.

Prevalence and influencing factors of anxiety and depression symptoms among surgical nurses during COVID-19 pandemic: A large-scale cross-sectional study.

AIM: To evaluate the prevalence and influencing factors of anxiety and depression symptoms in surgical nurses during the COVID-19 epidemic in Anhui, China. METHODS: A cross-sectional, multic'entre quantitative study was conducted among surgical nurses in Anhui province. SAS, SDS and SSRS scales were used for the investigation. Data were collected between 3 March 2020 to 19 March 2020. RESULTS: A total of 3,492 surgical nurses completed the survey. The average level of anxiety and depression of surgical nurses were higher than that of the Chinese norm. Levels of social support for surgical nurses were significantly negatively associated with the degree of anxiety and depression. Fertility status, participation in care for COVID-19 patients, likelihood of being infected with COVID-19 and social support were significantly influencing surgical nurses' anxiety degree. Similarly, these characteristics were significantly associated with the odds of depression symptoms in surgical nurses. CONCLUSION: These findings suggest that targeted psychological interventions to promote mental health of surgical nurses need to be immediately implemented.

Poor Neurological Deficit Was an Independent 30-day Risk Factor in Symptomatic Carotid Stenosis after CEA with Selective Shunting.

BACKGROUND: Carotid endarterectomy (CEA) prevents the occurrence of stroke in the future, although its efficacy depends on the detection and control of high perioperative risk factors. We aimed to analyze the association between preoperative neurological deficit and the 30-day risk of major adverse cardiovascular events (MACEs) in CEA with selective shunting for symptomatic carotid stenosis. METHODS: We assessed 653 patients who underwent CEA with selective shunting for symptomatic carotid stenosis between August 2011 and August 2019. The primary outcomes of the study were the occurrence of MACEs, defined as stroke (ischemic stroke or cerebral hemorrhage), all-cause mortality, and myocardial infarction during the perioperative period after CEA. Baseline patient characteristics were analyzed to identify factors associated with perioperative (<30 days) MACEs. Multivariable logistic regression models were used to estimate the association between preoperative modified Rankin Scale (mRS) and the 30-day risk of MACEs. Interaction and stratified analyses were conducted according to age, drinking, history of hypertension and coronary artery disease, and surgical side. RESULTS: The mean age of patients was 68.7 ± 9.1 years, and 86.4% were men. The 30-day MACEs rate was 2.5%. In univariate logistic regression, histories of coronary artery disease (odds ratio (OR), 2.57 [95% confidence interval (CI), 1.04-6.34]), a severe contralateral carotid stenosis or occlusion (OR, 4.52 [95% CI, 1.84-11.11]), and a poor neurological deficit (mRS ≥ 3 versus mRS < 3: OR, 3.78 [95% CI, 1.21-11.82]) were associated with higher primary outcome rates. A history of hypertension did not increase the risk of MACEs (OR, 0.37 [95% CI, 0.15-0.89]). In the multivariable regression analysis, poor neurological deficit was associated with a higher risk of the MACEs within 30 days (mRS ≥ 3 versus mRS < 3: 11.1% vs. 2.0%, adjusted OR 5.70 [95% CI, 1.50-21.60]). The interaction analysis revealed no interactive role in the association between neurological deficit and 30-day risk of MACEs. CONCLUSIONS: Poor neurological deficit was an independent risk factor associated with the 30-day risk of MACEs in symptomatic patients who underwent CEA with selective shunting. Our findings may provide guidance to surgeons when treating patients with poor neurological deficit. The decision to perform surgery should be made after careful consideration.

Clinical and Radiological Outcomes of Anterior Approach Microscopic Surgery for the Pincer Mechanism in Cervical Spondylotic Myelopathy.

OBJECTIVE: We aimed to evaluate the efficacy of anterior approach microscopic surgery for patients with the pincer mechanism in cervical spondylotic myelopathy. METHODS: The clinical data of pincer cervical spondylotic myelopathy that received anterior cervical decompression and fusion in our hospital from Aug 2014 to Dec 2017 were analyzed retrospectively, including 12 males and 9 females, with an average age of 64.3 years (range 46-81 years). Occupying rate, anterior occupying rate, and posterior occupying rate were measured on pre- and postoperative mid-sagittal MRIs. Pre- and postoperative Japanese Orthopedic Association (JOA) scores, intervertebral space height, and C2 to C7 Cobb's angle were analyzed. RESULT: Duration of follow-up was six months. The pre- and postoperative anterior occupying rate were averagely 38.6±8.5% and 12.9±5.5%, respectively, the posterior occupying rates were averagely 27.4±7.2% and 13.1±6.6%, respectively, and Cobb's angle changed from 15.3±8.0° to 22.7±7.9°. The intervertebral space height increased from 4.6±0.4mm to 6.5±0.4mm. JOA scores improved significantly by 59.4±34.0% at six months after surgery. CONCLUSION: Decompression by anterior microscopic surgery can increase spinal canal volume directly, recover intervertebral space height, and resize Cobb's angle, but decrease the posterior compression by ligament Flava indirectly. Anterior decompression under the microscope may provide an alternative surgical option for partial patients with the pincer mechanism in cervical spondylotic myelopathy.

External drains versus no drains after burr-hole evacuation for the treatment of chronic subdural haematoma in adults.

BACKGROUND: Chronic subdural haematoma (CSDH) is one of the most common types of intracranial haematoma, and often occurs in older people. Burr-hole craniostomy, which is an evacuation through one or two burr holes drilled over the site of the haematoma, has been widely accepted as the most effective way to manage CSDH. Recurrences are a major problem and need reoperation, sometimes repeatedly. OBJECTIVES: To assess the effects and safety of the use of external drains versus no drains after burr-hole evacuation for the treatment of CSDH in adults. SEARCH METHODS: We ran our first search on 27 November 2014. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S and CPSI-SSH), Chinese databases, and clinical trials registers, and screened reference lists. In compliance with the MECIR conduct standard 37, the Cochrane Injuries Group Information Specialist ran an update search within 12 months of publication (25 April 2016). We have screened these results but not incorporated the findings into the current review; as a result of the update search, one trial is awaiting classification. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared external subdural drains with no drains after burr-hole evacuation for the treatment of CSDH in adults. DATA COLLECTION AND ANALYSIS: Two review authors identified potential articles from the literature search, extracted data independently using a data extraction form and assessed risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, where statistical heterogeneity was low, we calculated summary risk ratios with 95% confidence intervals using a fixed-effect model. MAIN RESULTS: Nine RCTs, including a total of 968 participants, reported outcomes specified by this review. Only one RCT reported the use of an adequate method of allocation concealment; this trial was a large, single-centre, high quality study and was adequately reported. All included trials reported a reduced recurrence of CSDH with external subdural drains. We found a significant reduction in the risk of recurrence with subdural drains (RR 0.45, 95% CI 0.32 to 0.61, I(2) = 38%; 9 studies, 968 participants; moderate-quality evidence). There was no strong evidence of any increase in complications (RR 1.15; 95% CI 0.77 to 1.72, I(2) = 0%; 7 studies, 710 participants; low-quality evidence), mortality (RR 0.78, 95% CI 0.45 to 1.33, I(2) = 22%; 5 studies, 539 participants; low-quality evidence), or poor functional outcome (which included deaths) (RR 0.68, 95% CI 0.44 to 1.05, I(2) = 31%; 5 studies, 490 participants; low-quality evidence). AUTHORS' CONCLUSIONS: There is some evidence that postoperative drainage is effective in reducing the symptomatic recurrence of CSDH. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Due to the low quality of the evidence for the secondary outcomes, the effect of drainage on the occurrence of surgical complications, mortality and poor functional outcome is uncertain. This uncertainty can be clarified with data from high-quality studies which may be conducted in the future. There is no strong evidence of any increase in complications when drains are used.

Effects of electromagnetic fields from mobile phones on depression and anxiety after titanium mesh cranioplasty among patients with traumatic brain injury.

OBJECTIVE: To explore the effects of radiofrequency-electromagnetic fields (RF-EMFs) from mobile phones on depression and anxiety after titanium mesh cranioplasty among patients with traumatic brain injury (TBI). METHODS: Two hundred and twenty patients with TBI and titanium mesh cranioplasty who were hospitalized from 2008-2012 were recruited in this study. From November-December 2012, the relevant information was surveyed including socio-demographic characteristics, lifestyle variables, injury-related information, RF-EMF exposure of mobile phone, Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). Associations of RF-EMFs exposure after titanium mesh cranioplasty with SAS and SDS were respectively estimated by multivariable linear regression models. RESULTS: The patients with long durations of mobile phone use (ß = -6.6, p = 0.002), long individual call duration (ß = -5.3, p = 0.012), more daily calls (ß = -3.6, p = 0.027), invariably answer call immediately (ß = -3.9, p = 0.022) and high comprehensive exposure level (ß = -4.8, p = 0.003) had a lower score of depression compared with those without a mobile phone. Moreover, an ipsilateral and contralateral answering phone enhanced the protective effect on depression. Individuals with a long duration of mobile phone use had a lower score of anxiety (ß = -4.2, p = 0.008), while those with a bilateral answering phone had higher anxiety (ß = 3.9, p = 0.012) in comparison to those without a mobile phone. CONCLUSION: RF-EMFs after cranioplasty were significantly associated with the lower risk of depression and anxiety status among patients with TBI. Chronic and frequent RF-EMFs exposure may improve psychiatric disorders among patients with TBI.

Spontaneous thoracic ventral spinal subdural hematoma mimicking a tumoral lesion: a case report.

INTRODUCTION: Spinal subdural hematoma is rare and can cause serious neurological symptoms. Sometimes, idiopathic spinal subdural hematoma can spontaneously occur without any identifiable underlying etiologies. In this report, we present such an uncommon case of paraplegia caused by idiopathic spinal subdural hematoma that was successfully managed by laminectomy. CASE PRESENTATION: A 45-year-old Chinese woman presented with sudden onset of progressive asthenia and numbness in both lower extremities, accompanied by difficulty in micturition. An initial non-contrast spinal magnetic resonance imaging at a local hospital suggested a spinal subdural tumoral hematoma at the T9 level. She was referred to our hospital and an emergency laminectomy from T8 to T10 was performed 22 hours after onset of her initial symptoms. However, nothing but a hematoma was identified during the operation, and a final diagnosis of spontaneous acute spinal subdural hematoma was concluded. She had partial return of sensations and voluntary movement after the operation. CONCLUSIONS: On imaging findings, spinal subdural hematoma could manifest as focal and independent from the dura matter, and, therefore, it should be included in the differential diagnosis of medullary compressive lesions.

[Expression and function of autophagy after ischemia/reperfusion in rats hippocampus neuron].

OBJECTIVE: To explore the expression of autophagy after ischemia/reperfusion and its possible function in rats hippocampus neurons. METHODS: After 2 hours oxygen-glucose deprivation and different periods time of reperfusion (OGD/R) treatment in primary hippocampal neurons, neuron viability was evaluated by MTT assay, specific structure of autophagosome and specific protein of autophagy microtubule-associated protein 1 light chain 3 B (LC3B) were detected by transmission electron microscope and immunofluorescence respectively. The inhibitor of autophagy 3-Methyladenine (3-MA) was also used to exam the viability of neurons. RESULTS: Treatment by OGD/R markedly reduced neuronal viability. Compared to the control group, autophagy existed in different time periods after OGD/R shown both in transmission electron microscope and immunofluorescence. Application of 3-MA significantly reduced neuronal viability. CONCLUSION: Oxygen-glucose deprivation can activate autophagy in rat hippocampus neurons, which may resist the injury during ischemia/reperfusion.