Nucleophosmin 1 overexpression enhances neuroprotection by attenuating cellular stress in traumatic brain injury.

BACKGROUND: Traumatic Brain Injury (TBI) is a multifaceted injury that can cause a wide range of symptoms and impairments, leading to significant effects on brain function. Nucleophosmin 1 (NPM1), a versatile phosphoprotein located in the nucleolus, is being recognized as a possible controller of cellular stress reactions and could be important in reducing neuro dysfunction caused by TBI. However the critical roles of NPM1 in cellular stress in TBI remains unclear. METHODS: We employed a control cortical impact mouse model and a scratch-induced primary neuronal culture model. Hematoxylin and eosin staining was used to evaluate tissue damage and cellular changes, with NPM1 expression in the cortical area assessed through immunofluorescence staining and Western blot analysis. Neuronal morphology was assessed using Nissl staining. Behavioral assessments were performed to evaluate the impact of NPM1 overexpression on neurobehavioral results in TBI mice. Mitochondrial function was assessed using an Extracellular Flux Analyzer. RESULTS: Following TBI, an increase in NPM1 expression was observed, with a peak at 72 h post-injury. Increased levels of NPM1 resulted in decreased neuronal cell death, as shown by Nissl staining, and lower levels of Caspase 8, APE1, H2AX, and 8-OHDG expression, indicating a reduction in DNA damage. NPM1 overexpression also resulted in improved neurobehavioral outcomes, characterized by decreased neurological deficits and enhanced motor function post-TBI. Additionally, in vitro, scratch-induction experiments revealed that NPM1 overexpression mitigated mitochondrial damage, as evidenced by the downregulation of P53, BCL2, and Cyto C expression levels and improvements in mitochondrial respiratory function. CONCLUSION: These findings suggest NPM1 as a promising target for developing interventions to alleviate TBI-related cellular stress and promote neuronal survival.

LncRNA Anxa10-203 enhances Mc1r mRNA stability to promote neuropathic pain by recruiting DHX30 in the trigeminal ganglion.

BACKGROUND: Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. METHODS: A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. RESULTS: Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. CONCLUSIONS: LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression.

The protective effects of sevoflurane on subarachnoid hemorrhage.

Sevoflurane has become an important volatile anesthetic in clinic and has been widely studied in recent years. Numerous studies have demonstrated the efficacy of sevoflurane in safeguarding against brain damage across various domains. For example, it has played a neuroprotective role in subarachnoid hemorrhage (SAH), traumatic brain injury, and ischemia/reperfusion injury. The ensuing critique will focus on the significance of sevoflurane in experimental SAH and shed light on the underlying mechanisms. The findings of the current investigation demonstrate that sevoflurane possesses neuroprotective capabilities and clarify that it effectively attenuates secondary damage resulting from SAH through anti-inflammatory and anti-apoptotic pathways. More specifically, sevoflurane is observed to mitigate arterial vasospasm, diminish microvascular thrombosis, and alleviate cerebral edema. In light of these discoveries, we maintain that sevoflurane exhibits significant promise in the management of SAH, and it merits additional investigation to facilitate its prompt clinical implementation. Therefore, a thorough understanding of the neuroprotective properties of sevoflurane is beneficial to exploring novel therapeutic solutions for SAH and providing clinicians with alternative treatment modalities.

The efficacy and safety of general anesthesia vs. conscious sedation for endovascular treatment in patients with acute ischemic stroke: a systematic review and meta-analysis.

Background: Endovascular thrombectomy (EVT) is an important treatment for patients with acute ischemic stroke (AIS). A number of studies have suggested that anesthesia type (conscious sedation vs. general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes. Methods: PubMed, EMBASE, Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) that were performed to evaluate general anesthesia (GA) and conscious sedation (CS) up to May 30, 2023. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) were analyzed and calculated with a fixed effect model. Results: We pooled 930 patients from seven RCTs. We conducted a meta-analysis comparing the outcomes of GA and CS in the included trials. The rate of functional independence in the GA group was higher than that in the CS group (RR: 1.17, 95% CI: 1.00-1.35; P = 0.04; I2 = 16%). The GA group had a higher successful recanalization rate than the CS group (RR: 1.15, 95% CI: 1.08-1.22; P < 0.0001; I2 = 26%). The GA group had a higher pneumonia rate than the CS group (RR: 1.69, 95% CI: 1.22-2.34; P = 0.002; I2 = 26%). In addition, there was no significant difference between GA and CS with respect to the National Institutes of Health Stroke Scale (NIHSS) score at 24 h (P = 0.62), Modified Rankin Scale (mRS) score at 90 days (P = 0.25), intracerebral hemorrhage (P = 0.54), and mortality at 3 months (P = 0.61). Conclusion: GA demonstrated superiority over CS in achieving successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, it was also associated with a higher risk of pneumonia. Further studies, particularly those with long-term follow-ups, are necessary to identify precise strategies for selecting the appropriate anesthetic modality in EVT patients. Systematic review registration: INPLASY202370116.

Analysis of the efficacy of microdissection of paravebous sinus meningiomas invading large venous sinuses.

OBJECTIVE: The management of paravebous sinus meningiomas that invade major venous sinuses is a subject of debate, particularly concerning the necessity of complete resection of the tumor and reconstruction of the venous sinus. This article aims to demonstrate the outcomes of total removal of the lesion (including the invading venous sinus portion) and the effects of restoring or not restoring venous circulation in terms of recurrence of the tumor, mortality, and post-operative complications. METHODS: The authors conducted a study involving 68 patients with paravebous sinus meningiomas. Of the 60 parasagittal meningiomas, 23 were located in the anterior third, 30 in the middle third, and 7 in the posterior third. Additionally, 3 lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery, and the degree of venous sinus involvement was classified into six types. For type I meningiomas, the outer layer of the sinus wall was stripped off. For types II to VI, two strategies were employed: non-constitutional, wherein the tumor and affected venous sinuses were removed without repair, and reconstructive, wherein the tumor was completely removed and the venous sinuses were sutured or repaired. Karnofsky Performance Status (KPS) scale and Magnetic Resonance Venography (MRV) were utilized to assess the outcomes of the surgical procedures. RESULTS: The study group of 68 patients underwent complete tumor resection in 97.1%, with sinus reconstruction attempted in 84.4% of cases with sinus wall and sinus cavity invasion. The recurrence rate of this group was 5.9%, with follow-up ranging from 33 to 57 months. It was found that the recurrence rate was significantly higher in cases with incomplete resection than in those with complete resection. The overall mortality rate was 4.4%, with all cases resulting from malignant brain swelling due to the failure to perform venous reconstruction after resectioning of the meningioma type VI. Furthermore, 10.3% of patients experienced worsening symptoms of neurological deficits or complete loss of neurological function, with a significantly higher incidence in those without venous reconstruction than in the venous reconstruction group (P < 0.0001, Fisher test). No statistically significant pre-operative and post-operative KPS differences were observed in patients with type I to V. However, in patients with type VI (who did not receive venous reconstruction), the post-operative KPS score was significantly worse. CONCLUSION: The results of this study suggest the necessity of a complete resection of the tumor, including the invasive venous sinus component, as the recurrence rate was found to be relatively low at 5.9%. Moreover, patients who did not undergo venous reconstruction showed significant deterioration in their clinical condition compared to other subgroups, thus highlighting the importance of venous sinus reconstruction.

Metabotropic glutamate receptor 5-mediated inhibition of inward-rectifying K+ channel 4.1 contributes to orofacial ectopic mechanical allodynia following inferior alveolar nerve transection in male mice.

Inward-rectifying K+ channel 4.1 (Kir4.1), which regulates the electrophysiological properties of neurons and glia by affecting K+ homeostasis, plays a critical role in neuropathic pain. Metabotropic glutamate receptor 5 (mGluR5) regulates the expression of Kir4.1 in retinal Müller cells. However, the role of Kir4.1 and its expressional regulatory mechanisms underlying orofacial ectopic allodynia remain unclear. This study aimed to investigate the biological roles of Kir4.1 and mGluR5 in the trigeminal ganglion (TG) in orofacial ectopic mechanical allodynia and the role of mGluR5 in Kir4.1 regulation. An animal model of nerve injury was established via inferior alveolar nerve transection (IANX) in male C57BL/6J mice. Behavioral tests indicated that mechanical allodynia in the ipsilateral whisker pad lasted at least 14 days after IANX surgery and was alleviated by the overexpression of Kir4.1 in the TG, as well as intraganglionic injection of an mGluR5 antagonist (MPEP hydrochloride) or a protein kinase C (PKC) inhibitor (chelerythrine chloride); Conditional knockdown of the Kir4.1 gene downregulated mechanical thresholds in the whisker pad. Double immunostaining revealed that Kir4.1 and mGluR5 were co-expressed in satellite glial cells in the TG. IANX downregulated Kir4.1 and upregulated mGluR5 and phosphorylated PKC (p-PKC) in the TG; Inhibition of mGluR5 reversed the changes in Kir4.1 and p-PKC that were induced by IANX; Inhibition of PKC activation reversed the downregulation of Kir4.1 expression caused by IANX (p < .05). In conclusion, activation of mGluR5 in the TG after IANX contributed to orofacial ectopic mechanical allodynia by suppressing Kir4.1 via the PKC signaling pathway.

Radiographic evaluation of immature traumatized incisors following different endodontic treatments.

BACKGROUND/AIMS: Indirect pulp capping, pulpotomy, and apexification are three common endodontic treatments for immature traumatized incisors. They all affect tooth root development to some extent. The aim of this retrospective study was to compare the influence of these treatments on root development of immature permanent incisors following dental trauma. MATERIALS AND METHODS: Twenty-one indirect pulp capping, 48 pulpotomy, and 58 apexification cases with a mean age of 8.4 ± 1.0 years and median follow up of 12 months were included. NIH ImageJ with TurboReg plug-in was used to correct angular differences between the pre-operative and recall periapical radiographs, and to calculate variations of root length, dentin wall thickness, and apical closure. Kruskal-Wallis ANOVA followed by pairwise comparisons was applied to compare the radiographic variations. The type of apical closure was assessed qualitatively and analyzed using Fisher's exact test. RESULTS: The apexification group had a lower trend toward apical closure than the other two groups (P < .05). It also showed thinner dentin wall thickness compared with the pulpotomy group (P = .001). There was no significant difference between pulpotomy and indirect pulp capping in the trend to apical closure (P > .05) or dentin wall thickness (P = .775). There was no significant difference in the variation of root length among the three groups (P = .06). There was a moderate correlation between the treatment and the type of apical closure (Cramer's V Coefficient = .375). Pulpotomy tended to form a normal apical constriction rather than a calcific barrier while apexification showed the opposite inclination. Indirect pulp capping had no specific inclination toward any type of apical closure. CONCLUSIONS: Apexification resulted in an abnormal root development mostly by affecting the dentin wall thickness and apical closure. Pulpotomy was beneficial for normal root development of immature traumatized teeth.