Microvascular decompression (MVD) is the first-line surgery for common cranial nerve disorders like facial spasms and trigeminal neuralgia. As microsurgical tech advances, MVD is now used for rare brain and nerve disorders such as masseter spasms, oculomotor paralysis, neurogenic hypertension, pulsatile tinnitus, intermediate nerve pain, and laryngospasm, which often stem from nervevessel compression causing abnormal nerve conduction and damage. MVD restores normal nerve function by removing the offending vessels. This article mainly reviews the pathogenesis, diagnostic criteria, and treatment strategies of related rare diseases, and systematically explores the application of MVD in rare brain and nerve disorders, aiming to provide scientific basis for the selection of clinical treatment plans.
To investigate the effects of lipopolysaccharide (LPS) on gene expression levels in the BV2 microglial cell line using transcriptome sequencing and bioinformatics analysis, and to explore the function and mechanism of glucose-regulated protein 75 (GRP75) in neuroinflammation induced by traumatic brain injury (TBI).
Methods
BV2 cells were selected for the experiment and randomly divided into the control group and an LPS group. The control group did not receive any treatment, while the LPS group was treated with 1 μg/mL LPS for 6 h. Three biological replicates were set up for each experimental group. Transcriptome sequencing was performed on the two groups of cells.Bioinformatics analysis was used to screen for significantly differentially expressed genes (DEGs), and cluster analysis was performed on the significant DEGs to analyze the changes in the expression level of GRP75 in an in vitro cellular neuroinflammation model. The expression level of GRP75 was validated using qPCR and Western blotting. Fifteen healthy male SD rats were selected to construct TBI and Sham rat models. They were divided into sham operation group (Sham group), TBI 3 d group, TBI 7 d group, TBI 14 d group, and TBI 28 d group according to the double random number table method, with three rats in each group. Western blotting was used to detect the expression of GRP75 at different time periods. To investigate the mechanism of action of GRP75 in neuroinflammation, GRP75 overexpression experiments and GRP75 inhibition experiments were designed separately. In the GRP75 overexpression experiment,BV2 cells were transfected with empty vector plasmid (Vector) and GRP75 overexpression plasmid(GRP75-OE), and divided into Vector group, GRP75-OE group, Vector+LPS group, and GRP75-OE+LPS group; In the GRP75 inhibitor treatment experiment, BV2 cells were treated with 5 μg/mL GRP75 inhibitor MKT-077 for 18 h, and the cells were divided into CON group, MKT-077 group, LPS group, and LPS-MKT-077 group. Western blotting was used to detect the protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and phosphorylated nuclear factor kappa B P65 subunit(NF-κB P65) in each group of cells, and the effects of GRP75 overexpression and inhibition on the NF-κB pathway were analyzed.
Results
Transcriptomic analysis indicated that GRP75 protein expression levels in the LPS group were significantly lower than those in the control group (P<0.05). Validation experiments showed that GRP75 expression in the the LPS group was significantly lower than that in the control group (P<0.05). In TBI rat brain tissues, compared with the Sham group, the relative expression levels of GRP75 protein decreased in the TBI 3 d group, TBI 7 d group, TBI 14 d group, and TBI 28 d group (P<0.05). In experiments exploring the anti-inflammatory mechanism of GRP75, overexpression experiments of GRP75 showed that iNOS, COX-2, and phosphorylated NF-κB P65 levels were significantly reduced in the GRP75-OE+LPS group compared to the Vector+LPS group (P<0.05). The GRP75 inhibitor treatment experiment showed that iNOS, COX-2, and phosphorylated NF-κB P65 levels were significantly increased in the MKT-077+LPS group compared to the LPS group (P<0.05).
Conclusions
GRP75 expression is downregulated in TBI rat brain tissues and in vitro neuroinflammation models. Overexpression of GRP75 significantly reduces neuroinflammation, potentially by modulating the NF-κB pathway, thereby alleviating neuroinflammation following TBI and reducing secondary damage. GRP75 may therefore play a protective role in TBI and serve as a potential therapeutic target for mitigating TBI-induced neuroinflammation.
To explore the effect and mechanism of Wuling powder on hypoxia induced high altitude cerebral edema (HACE).
Methods
Forty healthy male SD rats were randomly divided into four groups using a random number table: normobaric normoxic group (NC group), high-altitude cerebral edema group (HACE group), low-dose Wuling powder intervention group (WP-L group), and high-dose Wuling powder intervention group (WP-H group), with 10 rats in each group. The NC group was normally housed under normal pressure and oxygen conditions, while the remaining three groups were housed in a low-pressure, low-oxygen animal chamber which simulated the low-temperature and hypoxic environment of the plateau at an altitude of 6000 m to establish a plateau cerebral edema model. The rats in WP-L and WP-H groups were given 260 and 780 mg/kg of Wuling powder by gavage continuously 4 d before and 3 d after entering the cabin, respectively. HACE group was given the same amount of physiological saline.After 7 d, the brain water content was measured using the dry wet mass method, and the degree of brain function damage in rats was evaluated using the modified neurological severity score (mNSS) and corner test. The level of superoxide dismutase (SOD) in the cortical brain tissue of rats was detected using the microcalorimetry method, and the level of malondialdehyde (MDA) was detected using the colorimetric method. The mRNA relative expression levels of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) in the cortical brain tissue of rats were detected using qPCR experiment. The expression of aquaporin-4 (AQP4), protein kinase D1 (PKD1), and hypoxia inducible factor-1α (HIF-1α)in the cortical brain tissue of rats was determined using Western blot experiment.
Results
After 72 h of low-temperature and low oxygen environment feeding, the brain water content of rats in the WP-L group and WP-H group was significantly lower than that in the HACE group, and the difference was statistically significant (P<0.05). The mNSS score of HACE group rats was significantly higher than that of NC group,and the proportion of left turn was significantly increased; the mNSS scores of rats in the WP-L and WP-H groups were significantly lower than those in the HACE group, and the proportion of left turn was significantly reduced, with statistically significant differences (P<0.05). The MDA level in the brain tissue of HACE group rats was significantly higher than that of NC group, and the SOD activity was significantly decreased; the MDA level in the brain tissue of rats in both WP-L and WP-H groups decreased significantly, while the SOD activity increased significantly, and the differences were statistically significant (P<0.05). The levels of IL-1β, IL-6, and TNF-α in the HACE group were higher than those in the NC group, while the mRNA levels of various inflammatory factors in the WP-L and WP-H groups were significantly lower than those in the HACE group, and the differences were statistically significant (P<0.05). The expression of AQP4, HIF-1α, and PKD1 proteins in the HACE group was significantly increased compared to the NC group; the expression of AQP4, HIF-1α, and PKD1 proteins in the WP-L and WP-H groups gradually decreased compared to the HACE group, and the differences were statistically significant (P<0.05).
Conclusions
Wuling powder can significantly reduce cerebral edema and neurological impairment in HACE rats, and its mechanism of action may be related to the modulation of the HIF-1α/PKD1 pathway to play a role in alleviating oxidative stress injury, reduce inflammatory response, and ultimately play a role in improving hypoxia-induced plateau cerebral edema.
To investigate the effect of gypenoside ⅩⅦ (GP-17) on neuroinflammation after post-traumatic stress disorder (PTSD) and explore its mechanism of action.
Methods
Twenty-four 8-week-old male SD rats were randomly divided into Control group, SPS group, GP-17 low-dose group(1 mg/kg), and GP-17 high-dose group (4 mg/kg), with 6 rats in each group. A single prolonged stress(SPS) modelling was carried out in all groups except Control group, followed by intraperitoneal injection of 1, 4 mg/kg in GP-17 treatment group, and equal amount of saline was given intraperitoneally in Control group as well as in SPS group. After 7 d of SPS modeling, the fear status of PTSD rats was assessed using a capture refusal score and a fear condition test. Enzyme linked immunosorbent assay (ELISA) kit was used to detect the protein expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α),RT-qPCR was used to detect the mRNA expression of the above inflammatory factors. Immunofluorescence staining was used to detect the expression of microglial polarization marker INOS. Western blot was used to detect the relative expression levels of pathway related proteins phospho-protein kinase B (p-AKT),phospho-nuclear factor kappa B (p-P65), and phospho-inhibitor of nuclear factor-κB kinase α/β (p-IKKα/β).
Results
After 7 d of SPS modeling, the refusal score and freezing time of SPS group, GP-17 low-dose group, and high-dose group were significantly higher than those of the control group. The refusal score and freezing time of the GP-17 low-dose group and high-dose group were significantly lower than those of the SPS group, and the differences were statistically significant (P<0.05). ELISA and RT-qPCR results showed that the expression of IL-1β, IL-6, and TNF-α in the brain tissue of GP-17 low-dose and highdose groups after modeling was lower than that of SPS group at the RNA and protein levels (P<0.05), with the exception of IL-1β expression in the low-dose GP-17 group (P>0.05). Immunofluorescence results showed that the expression of the M1 polarization marker INOS in microglia in GP-17 low-dose and highdose groups was significantly lower than that in SPS group (P<0.05). Western blot results showed that compared with the SPS group, the expression levels of p-IKKα/β, p-AKT, and p-P65 were significantly decreased in both GP-17 high-dose group and low-dose groups (P<0.05), with the exception of the expression level of p-IKKα/β in the GP-17 low-dose group (P>0.05).
Conclusions
GP-17 attenuates panic behaviour and inhibits the expression of IL-1β, IL-6 and TNF-α in prefrontal cortex of PTSD rats,and also inhibits the expression of M1-type marker INOS in BV2 cells, which exerts neuroprotective effects, and the mechanism of its action may be related to the inhibition of neuroinflammation mediated by the AKT/NF-κB inflammatory pathway.
To investigate the protective effect of curcumol against apoptosis and its mechanism of action on cortical cells after post-traumatic stress disorder (PTSD) in rats.
Methods
Twelve healthy male SD rats were divided into blank control group, SPS group and curcumin group according to the randomized numerical table method, and the curcumin group was divided into a low concentration group (2.0 mg/kg) and a high concentration group (4.0 mg/kg) according to different concentrations, with three rats in each group. The SPS group and the curcumol group were subjected to single prolonged stress to establish the SPS model, and the conditioned fear test for the fearfulness of the rats was performed on the 7th day. The curcumol group was injected continuously intraperitoneally[2.0 and 4.0 mg/(kg·d)] 7 d after SPS modeling, while the SPS group was only intraperitoneally injected with physiological saline, the control group did not receive any treatment. Cerebral cortex tissue specimens were collected from rats after execution. Western blotting was used to detect the effects of drug intervention on the protein expression levels of phosphorylation of the eukaryotic initiation factor 2 (p-eif2a), the eukaryotic initiation factor 2 (eif2a), C/EBP-homologous protein (CHOP), and β-actin; Use an enzyme-linked immunosorbent assay kit to detect changes in the expression levels of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α); TUNEL cell apoptosis staining was used to detect the apoptosis of cells in the medial prefrontal cortex of rats;Pharmacotoxicity of curcumol on neuroglia was detected by live-dead cell staining and flow cytometry.
Results
After 7 d of SPS modelling, the results of the conditional fear box test showed that the freezing time percentage of the SPS group rats was significantly higher than that of the control group, and the freezing time percentage of curcumin group was significantly lower than that of the SPS group, with statistical significance (P<0.05). The Western blotting results showed that the levels of p-eif2a and CHOP proteins in the SPS group were significantly higher than those in the control group, while the levels of p-eif2a and CHOP proteins in the low concentration and high concentration groups of curcumin were significantly lower than those in the SPS group, with statistical significance (P<0.05). The ELISA detection results showed that the levels of IL-1β, IL-6, and TNF-α in the SPS group were significantly increased compared to the control group, while the levels of IL-1β, IL-6, and TNF-α in the high concentration group of curcumin were significantly decreased compared to the SPS group, with statistical significance (P<0.05). The apoptosis rate of cells in the SPS group was significantly higher than that in the control group, while the apoptosis rate of cells in the high concentration group of curcumin was significantly lower than that in the SPS group, and the differences were statistically significant (P<0.05).CCK-8 detection showed that after co culturing with 2 μg/mL curcumin solution for 0, 3, 6, 12, and 24 h,there was no significant change in the activity of microglia at each time point, and no obvious dead cells were observed.
Conclusions
Curcumol was able to inhibit the fear freezing state in rats after PTSD,exerting neuroprotective effects and inhibiting neuroinflammation, and its mechanism of action may be related to the inhibition of the expression of the eif2a-CHOP endoplasmic reticulum stress pathway and the inhibition of apoptosis by curcumol.
To analyze the influencing factors of prognosis in elderly patients with acute ischemic stroke accompanied by cardiac fibrillation.
Methods
Using the method of cluster sampling, 112 elderly patients with acute ischemic stroke accompanied by atrial fibrillation who visited the Institute of Neurotrauma and Repair, Characteristic Medical Center of Chinese People's Armed Police Force from April 2021 to May 2024 were selected as the research objects. According to the prognosis of patients treated for 6 months, they were divided into a good prognosis group and a bad prognosis group.The clinical data, laboratory test results, and long-term incidence of cardiovascular adverse reactions were collected and compared between two groups of patients, and multiple Logistic regression analysis was used to screen the factors affecting the prognosis of elderly patients with acute ischemic stroke and atrial fibrillation.
Results
There were 59 cases in the good prognosis group and 53 cases in the poor prognosis group. Univariate analysis showed that BMI, cerebral infarction volume, smoking history,diabetes history, hypertension history, previous cardiovascular and cerebrovascular history, family history of coronary atherosclerotic heart disease, peripheral vascular disease history, total bilirubin, triglycerides(TG), low-density lipoprotein (LDL), urea nitrogen, gamma-glutamyl transferase (GGT), D-dimer (D-D),eosinophil count, cerebral infarction volume, National Institutes of Health stroke scale (NIHSS) score between two groups were statistically significant (P<0.05). Multivariate Logistic regression analysis showed that smoking history, hypertension history, elevated TG levels, elevated LDL levels, elevated urea nitrogen levels, elevated GGT levels, elevated D-D levels, elevated eosinophil count, stroke volume ≥100 mL, and elevated NIHSS score were independent risk factors for elderly patients with acute ischemic stroke with atrial fibrillation (P<0.05).
Conclusions
The overall prognosis of elderly patients with acute ischemic stroke and atrial fibrillation is poor. Smoking history, hypertension history, TG, LDL, urea nitrogen, GGT,D-D, eosinophilic counts may have a certain impact on the prognosis of elderly patients with acute ischemic stroke accompanied by atrial fibrillation.
To investigate the application effects of the fast track surgery (FTS)concept in patients undergoing microvascular decompression (MVD) surgery for trigeminal neuralgia.
Methods
A retrospective study was conducted on 123 TN patients with MVD admitted to Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force from January 2022 to January 2024, 59 patients admitted from January 2022 to January 2023 were included in the control group, and 64 patients admitted from February 2023 to January 2024 were included in the observation group. The control group received conventional perioperative interventions, while the observation group was managed with the FTS concept in addition to conventional care. Postoperative complications, pain scores, anxiety and depression levels, sleep quality, and quality of life between the two groups of patients were compared.
Results
After 7 d of surgery, the incidence of postoperative complications in the observation group was lower than that in the control group, except for intracranial infection, there was a statistically significant difference in the incidence of other complications (high fever, headache, nausea and vomiting, urinary tract infection) (P<0.05). On postoperative days 1 and 7,the visual analog scale (VAS) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale(SDS) scores, and Pittsburgh sleep quality index (PSQI) scores of both groups of patients decreased compared to admission, and the observation group was lower than the control group, with statistical significance (P<0.05). After 7 d of surgery, the quality of life scores of both groups of patients increased compared to admission, and the observation group was higher than the control group, with statistical significance (P<0.05).
Conclusions
The application of FTS concept in TN patients undergoing MVD can reduce the incidence of postoperative complications, alleviate pain, anxiety, and depression, improve sleep quality and quality of life. This approach is safe and effective.
As an organophosphorus nerve agent, soman exerts its neurotoxic effects by irreversibly inhibiting acetylcholinesterase activity. This inhibition leads to the accumulation of acetylcholine at neural synapses and neuromuscular junctions, triggering persistent epileptic states and potentially fatal symptoms such as respiratory failure. Despite the existence of standard treatment protocols, their efficacy heavily relies on early intervention, as delayed treatment often fails to prevent neurological damage and death. Even with timely administration of medication, uncontrolled epileptic activity within 20 min can cause widespread neuropathological damage across multiple brain regions, significantly increasing the mortality rate. Further exploration of novel combination therapy strategies, expansion of the therapeutic time window, and improvement of outcomes for delayed treatment are crucial for emergency response to soman poisoning. This article provides a comprehensive review of the neurotoxic mechanisms of soman and recent advancements in therapeutic drugs, aiming to offer a reference for the further development of new treatment strategies for soman poisoning.
To establish biomarkers for diabetic peripheral neuropathy (DPN) by analyzing plasma transcriptomic profiles and elucidate its underlying mechanisms.
Methods
A prospective clinical cohort study was carried out. A total of 83 subjects were included, including 33 patients with DPN (DPN group) who visited the Neurosurgery Department of China-Japan Friendship Hospital from January to September 2023, 30 healthy subjects (NDM group) and 20 patients with type Ⅱdiabetes (DM group) who were recruited from community near China-Japan Friendship Hospital at the same time. Demographic and clinical information of all subjects were evaluated, and blood samples of 60 patients were sent for plasma transcriptomic sequencing by propensity matching. Feature screening was performed by differential analysis and multiple machine learning algorithms (Lasso regression, Logistic regression, SVM and XGBoost) to establish biomarkers that can predict the occurrence of DPN. Based on key gene features, the possible mechanism of DPN was studied.
Results
A total of 133 differentially expressed genes related to DPN were identified. Through feature screening using Lasso regression,Logistic regression, SVM, and XGBoost, 47 key gene features highly correlated with the occurrence of DPN were identified. GO enrichment and KEGG pathway enrichment analysis showed that 35 genes were associated with protein binding function (P=0.010). The correlation analysis results showed that these genes were significantly correlated with the severity of neuropathy and pain symptoms (P<0.05). GO enrichment and KEGG pathway enrichment analysis showed that the B cell receptor signaling pathway and insulin resistance pathway were significantly enriched, playing a core role in the pathogenesis of DPN.
Conclusions
Based on plasma transcriptomics and multidimensional clinical scales, 47 key gene markers of DPN were revealed, confirming that insulin resistance and abnormal B cell receptor signaling are the core mechanisms of DPN.