Blood brain barrier (BBB) injury is the main pathological manifestation of many neurological diseases. Glycocalyx is the gel layer covering the lumen side of vascular endothelial cells, which plays an important role in regulating BBB function. However, glycocalyx is very fragile and easily damaged in various neurological diseases, leading to BBB destruction. This article focuses on the potential role of glycocalyx in cerebrovascular disease, the possible mechanisms related to glycocalyx and BBB injury, and explores the potential therapeutic strategies for protecting and restoring endothelial glycocalyx.

Objective:To investigate the protective effect and related mechanisms of Huatuo Zaizao pills (HT) on white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in mice. Methods:Forty adult male C57BL/6J mice were randomly divided into sham-operation group, bilateral carotid artery stenosis (BCAS) model group, and HT group. An animal model of BCAS was constructed using the spring loop into the bilateral common carotid arteries. After continuous treatment with 5 g/kg HT (or an equal amount of purified water) for 4 weeks, cognitive function was evaluated using the novel object recognition test. Morphological and structural changes in myelin sheath were evaluated by LFB myelin staining. White matter damage and glial cell expression were detected by myelin associated glycoprotein (MAG) in the corpus callosum, ionized calcium-binding adapter molecule 1 (IBA-1), and glial fibrillar acidic protein (GFAP) in corpus callosum and hippocampus through immunofluorescence staining. Real time quantitative polymerase chain reaction (qPCR) was used to detect mRNA expressions of myelin-associated proteins, Janus kinase 2 (JAK2), signal transducer and activator of the transcription 3 (STAT3) in corpus callosum, as well as brain-derived neurotrophic factor (BDNF), glutathione peroxidase 1 (GPx-1), and various inflammatory factors in hippocampus.Results:The novel object recognition test showed that mice had significant working memory impairment at 4 weeks after BCAS ( P<0.01), while the HT group showed significant improvement in working memory impairment compared to the BCAS group ( P<0.01). LFB myelin staining showed significant myelin damage in the BCAS group ( P<0.001), while the degree of myelin damage in the HT group was significantly improved compared to the BCAS group. Immunofluorescence staining showed that both the BCAS and HT groups had proliferation of microglia in the corpus callosum and hippocampus, and there was no significant difference between the two groups. In contrast, the activation of astrocytes in the corpus callosum was significantly improved in the HT group compared to the BCAS group ( P<0.05). qPCR showed upregulation of myelin-associated proteins as well as JAK2 and STAT3 mRNA expression in the BCAS group. Compared with the BCAS group, the expressions of JAK2 and STAT3 mRNA were decreased in the HT group (all P<0.05), while the expression of myelin-associated proteins were upregulated (all P<0.05). There were no significant difference in the expressions of inflammatory factors, BDNF, and GPX1 mRNA in the hippocampal tissue between the BCAS group and the HT group. Conclusion:HT may improve cognitive impairment and white matter damage in mice with chronic cerebral hypoperfusion, and the JAK2-STAT3 pathway may be one of its effect pathways.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.

Malignant cerebral edema (MCE) can lead to deterioration of neurological function in patients with acute ischemic stroke, and significantly increase the mortality and disability rate. Therefore, early detection and intervention of MCE is crucial for saving patients' lives. This article reviews the predictors and preventive scales of MCE after acute ischemic stroke.

Although endovascular therapy improves the recanalization rate of acute large vessel occlusive ischemic stroke, about half of the patients still have poor functional outcome at 90 d, which is called " futile recanalization" . This article reviews and summarizes the predictive factors of futile recanalization after endovascular therapy in acute anterior circulation ischemic stroke, in order to provide help for clinical work and scientific research in the future.

OBJECTIVE: To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord. METHODS: The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time. RESULTS: The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed ( < 0.01), and spontaneous discharge frequency was obviously reduced ( < 0.01, =12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures ( < 0.01, =6). CONCLUSIONS etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.
Animals ; Animals, Newborn ; Etomidate ; Neurons ; Patch-Clamp Techniques ; Rats ; Spinal Cord

Objective To analyze the influence of general anesthesia (GA) on bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson's disease (PD) through microelectrode recording (MER),and discuss the differences between different modes of anesthesia.Methods A retrospective analysis was performed on clinical data of 31 PD patients accepted bilateral STN-DBS in our hospital from June 2015 to June 2017.Nine patients accepted surgery under GA (A group):4 patients were treated with intravenous anesthesia (A1 group),and 5 patients were treated with inhalation anesthesia (A2 group);22 patients accepted surgery under local anesthesia LA group.MER indexes,including STN discharge frequency,STN recorded length,and maximum target error,and short-term (6 months) efficacy were recorded.A linear regression analysis was performed to find possible influence factors on discharge frequency and improving rate of UPDRS scores.Results The discharge frequencies of B group,A1 group and A2 group were 51.42 Hz±6.28 Hz,35.79 Hz±7.02 Hz and 43.18 Hz±5.87 Hz,respectively,with significant differences (F=12.181,P=0.000);as compared with that in the B group,the discharge frequencies of A1 group and A2 group were significantly lower (P＜0.05).The STN recorded lengths of B group,A1 group and A2 group were 5.48 mm±0.33 mm,5.06 mm±0.15 mm and 5.22 mam±0.16 mm,respectively,with significant differences (F=4.115,P=0.027);as compared with that in the B group,the recorded lengths of A1 group and A2 group were significantly shorter (P＜0.05).A1 group had the maximum target error,but no significant differences were noted among the 3 groups (P＞ 0.05).Six months after the surgery,the UPDRS-Ⅲ scores and Schwab-England scores of A group and B group were decreased and daily levodopa equivalent (LEDD) was decreased.As compared with B group,A group had significantly better improvement in Hoehn & Yahr grading (P＜0.05).Disease durations were positively correlated with discharge frequency (r=0.539,P=0.002);age and improving rate of UPDRS scores were negatively correlated (r=-0.572,P=-0.001);preoperative LEDD and improving rate of UPDRS scores were positively correlated (r=0.725,P=-0.000).Conclusions Bilateral STN-DBS performed under GA in PD enjoys good efficacy,which shows no obvious difference as compared with that under LA.Inhalation anesthesia had less influence on electrophysiology than intravenous anesthesia.

Objective To investigate the predictive value of C-reactive protein/albumin ratio (CAR) for 30 d survival status in patients with acute ischemic stroke.Methods Patients with acute ischemic stroke admitted to the Neurological Intensive Care Unit (NICU),Nanfang Hospital,Southern Medical University were selected from 2013 to 2016.They were divided into a survival group and a death group according to the 30 d survival status.The clinical data of both groups were compared and analyzed.Multivariate logistic regression analysis was used to determine the independent risk factors for 30 d survival status.The predictive value of the variables was analyzed using the receiver operating characteristic (ROC) curve.Results A total of 236 patients were enrolled in the study,including 64 (27.12％) in the death group and 172 (72.88％) in the survival group.The baseline National Institutes of Health Stroke Scale score,procalcitonin,C-reactive protein,CAR,and onset to NICU time in patients of the survival group were significantly lower or shorter than those of the death group,and the serum albumin level of the survival group was higher than that of the death group (all P ＜0.05).Pearson's correlation analysis showed that C-reactive protein (r =0.647,P ＜ 0.001),CAR (r =0.632,P ＜ 0.001),and onset to NICU time (r =0.596,P ＜ 0.001) were closely associated with the 30 d survival status in patients with acute ischemic stroke.Multivariate logistic regression analysis showed that CAR was an independent risk factor for 30 d mortality in patients with acute ischemic stroke (odds ratio 1.895,95％ confidence interval 1.573-2.282;P ＜ 0.001).ROC curve analysis showed that the area under the curve of CAR was 0.873 (95％ confidence interval 0.815-0.931),the optimal cut-off value was 2.197,the sensitivity of predicting 30 d death risk was 82.8％,and the specificity was 87.8％.Conclusion CAR is an independent risk factor for 30 d death in patients with acute ischemic stroke and can be used for 30 d survival assessment in patients with acute ischemic stroke.

Objective To study the neuroprotective role of TFP5 in a MPTP-induced mouse model of Parkinson's disease (PD).Methods C57BL/6 mice were used as experimental animals.Briefly, 5 consecutive days of intraperitoneal injection of 25 mg/Kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to induce mouse PD model.The mice were randomized into 5 groups including control group,model group, scrambled TFP5 peptide (Scb) group, TFP5 group and roscovitine group.On the 7th day after the first injection of MPTP,behavior tests were performed, and then western blot method was employed to detect the expression of p25 and phosphorylated MEF2D in substantia nigra.Tyrosine hydroxylase (TH) immunohistochemical staining was performed to observe the apoptosis of dopaminergic neurons in substantia nigra pars compacta (SNpc) 28 days after the first injection of MPTP.Results MPTP increased the expression of p25 (0.48±0.10 vs 0.26±0.02, P＜0.05) and phosphorylated MEF2D (0.81±0.10 vs 0.22±0.02, P＜0.05) in substantia nigra, but decreased the number of dopaminergic neurons in SNpc (348.67±24.40 vs 463.29± 19.61, P＜0.05),resulting in motor impairment in the model mice (P＜0.05).Intraperitoneal injection of 30mg/Kg of TFP5 for 3 days effectively reduced the excessive phosphorylation of MEF2D (0.25 ± 0.12 vs 0.81 ± 0.10, P＜ 0.05) in substantia nigra, rescued dopaminergic neuron reduction of SNpc (422.92±8.41 vs 348.67±24.40, P＜0.05), and improved the motor ability of the model mice (P ＜0.05).Roscovitine exerted almost same neuroprotective role as TFP5 ,while Scb had no protective effect.Conclusion TFP5 can rescue MPTP-induced damage of dopaminergic neurons in substantia nigra, and thus improve motor impairment of model mice,which may be mediated by the inhibition of Cdk5/p25 activity.