A case of NMDAR Encephalitis with muscular pain as the main presentation.

BACKGROUND: Persistent somatoform pain disorder (PSPD) is often the initial diagnosis in patients seeking treatment in psychiatric departments, making it challenging to consider organic nervous system diseases. However, autoimmune encephalitis can present with atypical initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture, with antibody support, plays a crucial role in diagnosing autoimmune encephalitis. CASE PRESENTATION: This report describes a 40-year-old male adult patient who was initially diagnosed with persistent somatoform pain disorder in 2022. The patient reported a reduction in pain while resting on his back. There were no fever or relevant medical history. Despite 8 months of symptomatic treatment, the symptoms did not improve. Moreover, the patient developed confusion, gibberish speech, non-cooperation during questioning, and increased frequency and amplitude of upper limb convulsions. Lumbar puncture revealed elevated protein levels and protein-cell dissociation. The autoimmune encephalitis antibody NMDAR (+) was detected, leading to a diagnosis of autoimmune encephalitis (NMDAR). CONCLUSION: Autoimmune encephalitis (NMDAR), starting with persistent somatoform pain (PSPD), often presents with atypical symptoms and can be easily misdiagnosed. Therefore, it is important to consider the possibility of organic nervous system disease in time, and to test serum or cerebrospinal fluid antibodies to rule out organic nervous system disease after symptomatic treatment of mental disorders is ineffective. This approach facilitates the early diagnosis of autoimmune encephalitis and other underlying organic neurological disorders.

Human urinary kallidinogenase decreases the incidence of post-stroke cognitive impairment in acute ischemic stroke patients.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a common symptom of stroke and affects the quality of life and prognosis of stroke survivors. In our study, we evaluated the efficacy of Human urinary kallidinogenase (HUK) on cognitive function in acute ischemic stroke (AIS) patients, and discussed the role of cystatin C (CysC) in improving PSCI. METHODS: We enrolled a retrospective cohort with prospective follow-up. From August 2020 to May 2021, 130 patients completed the final follow-up. Among them, 61 patients received HUK combined with basic treatment, which we defined as the HUK group, and 69 patients received basic treatment, which we defined as the control group. We compared the changes of CysC, urea nitrogen and creatinine levels after one week of treatment between the two groups. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at 3-month after AIS. RESULTS: No significant differences in demographic data and Laboratory tests between two groups before treatment. A total of 67 patients (51.5%) were diagnosed as PSCI at 3-month follow-up, among which, 25 patients were in the HUK group and 42 patients were in the control group. Compared with the control group (60.9%), the incidence of PSCI was significantly lower in the HUK group (41.0%). In addition, the serum CysC level after a week of treatment significantly decreased from baseline in HUK group (p = 0.037), in comparison, the serum CysC level in the control group was basically unchanged (p = 0.951). There was a significant negative correlation between MoCA score and the level of CysC after treatment (p = 0.003, r = -0.373). CONCLUSIONS: HUK can reduce the risk of PSCI at 3-month in AIS patients. The decrease of serum CysC level may be one of the mechanisms by which HUK reduces the incidence of PSCI.

Clinical-radiological dissociation in a patient with nitrous oxide-induced subacute combined degeneration: a case report.

BACKGROUND: Several recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, the association between the evolution of dynamic neuroimaging and clinical manifestations has not been reported in patients with N2O-induced SCD. CASE PRESENTATION: We described the case of a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and serum vitamin B12 levels exceeded the normal levels. However, the hyperintensities had extended horizontally and longitudinally on T2-weighted magnetic resonance imaging (MRI), compared to those on the initial scan. Two months after treatment, the patient experienced some residual numbness in the distal limbs, and his serum homocysteine levels were normal, but the abnormal signals seen on cervical T2-weighted MRI had decreased only slightly compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged compared to the clinical manifestation, which was suggestive of a clinical-radiological dissociation. CONCLUSIONS: Clinical-radiological dissociation might have occurred in this case because T2-weighted imaging was not sensitive enough to reveal cytotoxic edema. Moreover, the serum vitamin B12 level is not a good indicator of cellular vitamin B12. Thus, clinicians should recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.

The role of LINC00094/miR-224-5p (miR-497-5p)/Endophilin-1 axis in Memantine mediated protective effects on blood-brain barrier in AD microenvironment.

The dysfunction of the blood-brain barrier (BBB) is one of the main pathological features of Alzheimer's disease (AD). Memantine (MEM), an N-methyl-d-aspartate (NMDA) receptor antagonist, has been reported that been used widely for AD therapy. This study was performed to demonstrate the role of the MEM in regulating BBB permeability in AD microenvironment as well as its possible mechanisms. The present study showed that LINC00094 was dramatically increased in Abeta1-42 -incubated microvascular endothelial cells (ECs) of BBB model in vitro. Besides, it was decreased in MEM-incubated ECs. Silencing LINC00094 significantly decreased BBB permeability, meanwhile up-regulating the expression of ZO-1, occludin and claudin-5. Furthermore, silencing LINC00094 enhance the effect of MEM on decreasing BBB permeability in AD microenvironment. The analysis of the mechanism demonstrated that reduction of LINC00094 inhibited Endophilin-1 expression by up-regulating miR-224-4p/miR-497-5p, promoted the expression of ZO-1, occludin and claudin-5, and ultimately alleviated BBB permeability in AD microenvironment. Taken together, the present study suggests that the MEM/LINC00094/miR-224-5p (miR-497-5p)/Endophilin-1 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment. Silencing LINC00094 combined with MEM provides a novel target for the therapy of AD.

miR-424-5p maybe regulate blood-brain barrier permeability in a model in vitro with Abeta incubated endothelial cells.

The blood-brain barrier (BBB) in AD patients and in animal models is changed. However, the mechanisms are still unclear. Here, we found that miR-424-5p was upregulated in Abeta-incubated microvascular endothelial cells. TEER and HRP exudation tests showed that miR-424-5p silencing significantly decreased BBB permeability in vitro BBB model with Abeta-incubated. MiR-424-5p silencing upregulated expression of the tight junction proteins, ZO-1 and occludin in Abeta-incubated microvascular endothelial cells. Furthermore, dual luciferase reporter gene assay results confirmed the presence of a potential binding site for miR-424-5p on the 3'UTR of Endophilin-1. Endophilin-1 was down-regulated in Abeta-incubated endothelial cells in which miR-424-5p was silenced. In conclusion, the present study demonstrates that miR-424-5p could affect the expression of tight junction proteins (ZO-1 and occludin) via Endophilin-1 and thereby maybe regulate BBB permeability in an BBB model in vitro with Abeta incubated endothelial cells. MiR-424-5p may thus serve as a protective target for AD and provide a new strategy for the prevention and treatment of AD.

Comparison of Motor Relearning Program versus Bobath Approach for Prevention of Poststroke Apathy: A Randomized Controlled Trial.

BACKGROUND: Apathy is a multidimensional syndrome referring to a primary lack of motivation, frequent in survivors of stroke. And prior studies have demonstrated the negative effect of apathy on recovery from stroke. METHODS: A randomized controlled study of acute stroke patients. Four hundred and eighty-eight patients without evidence of apathy or depression at the initial visit were consecutively recruited, 258 males and 230 female. Patients were block randomized into 2 groups. Group A (n = 245) and Group B (n = 243) had physiotherapy according to Motor Relearning Program and Bobath in the first 4 weeks, respectively. The supplemental treatment did not differ in the 2 groups. Patients were assessed with Apathy Evaluation Scale-Clinical, National Institutes of Health Stroke Scale scores, Barthel Index scores, Mini-Mental State Examination scores, Hamilton Depression Scale scores, and Hamilton Anxiety Scale scores upon admission. At 1-, 3-, 6-, 9-, and 12-month follow-up after stroke, patients were assessed for diagnosis and severity of apathy using the Apathy Evaluation Scale-Clinical. RESULTS: Baseline characteristics of the subjects are age mean 65.1 (standard deviations, SD 10.9); 47.1% female; Apathy Evaluation Scale-Clinical mean 24.9 (SD 4.7); National Institutes of Health Stroke Scale mean 3.9 (SD 3.8); Barthel Index mean 87.9 (SD 8.7); Mini-Mental State Examination mean 23.3 (SD 4.5); Hamilton Depression Scale mean 17.5 (SD 6.6); and Hamilton Anxiety Scale mean 14.4 (SD 6.2). Participants in both groups had similar levels of apathy symptoms at study admission (Motor Relearning Program, mean = 24.78, SD = 4.62; Bobath, mean = 25.07, SD = 4.75). The Apathy Evaluation Scale scores of participants in both groups demonstrated to decline gradually from month 1 to month 12. Motor Learning Program participants had significantly less apathy severity compared with Bobath participants with respect to each time point. Participants given Bobath approach were 1.629 times more likely to develop poststroke apathy than patients given Motor Relearning Program over 12 months. CONCLUSIONS: Physiotherapy treatment in acute stroke rehabilitation using Motor Relearning program was significantly more effective in preventing of new onset of apathy following stroke compared with Bobath approach.

S14G-humanin alleviates insulin resistance and increases autophagy in neurons of APP/PS1 transgenic mouse.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aß plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport, and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aß deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels. Our results demonstrated that HNG could improve the learning ability and memory in APP/PS1 transgenic mice, possibly through decreasing IRS-1 Ser636 phosphorylation and mTOR protein expression in the hippocampus, thus improving insulin resistance in the brain. In addition, HNG increased ULK1 expression, decreased p62 and LC3 I/LC3 II protein levels, thus enhancing autophagy and decreasing Aß deposition in the brain. Taken together, our results suggest that through the regulation of IRS-1/mTOR insulin signaling in the hippocampus, HNG increases the activity of autophagy and decreases Aß deposition in the brain, and improves learning ability and memory of AD mice.

Up-regulation of Ca2+/CaMKII/CREB signaling in salicylate-induced tinnitus in rats.

The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-D-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p < 0.05), and the free intracellular Ca2+ concentrations (p < 0.05). Our data reveal that salicylate administration causes tinnitus symptoms and elevates Ca2+/CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.

C-Reactive Protein Can Be an Early Predictor of Poststroke Apathy in Acute Ischemic Stroke Patients.

BACKGROUND: Apathy is a multidimensional syndrome referring to a primary lack of motivation that occurs frequently in survivors of stroke. Higher C-reactive protein (CRP) level was associated with higher apathy scores among Alzheimer disease cases. However, data on the relationship between CRP levels and apathy in patients with stroke are lacking. So, we hypothesized an association between CRP and poststroke apathy (PSA). METHODS: Two hundred ninety-two consecutive patients with stroke were recruited within 7 days after stroke. Apathy symptoms were assessed at baseline and at 1, 3, and 6 months after stoke using the Apathy Evaluation Scale-Clinical (AES-C). Demographic and clinical information were obtained using the National Institutes of Health Stroke Scale (NIHSS) scores, Barthel Index (BI) scores, Mini-Mental State Examination (MMSE) scores, Hamilton Depression Scale (HAMD) scores, and Hamilton Anxiety Scale (HAMA) scores. CRP was measured at baseline. The presence and the location of infarcts were evaluated using magnetic resonance imaging. RESULTS: Apathy at baseline was significantly associated with body mass index (BMI), NIHSS, BI, MMSE, HAMD, and CRP (P < .05) upon admission. PSA at 6 months was significantly associated with elevated CRP concentrations, high AES-C score, and low BI score (P < .05) upon admission. The AES-C scores peaked 3 months after stroke, but then abated over 6 months. CONCLUSIONS: CRP, BMI, MMSE, depression, and disability are closely related to apathy during the acute stage of ischemic stroke. Lower BI scores, higher CRP concentrations, and apathy in acute stroke phase increased the risk of PSA at 6 months.

Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson's Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway.

BACKGROUND/AIMS: Parkinson's disease (PD) is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB), an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. METHODS: PD was introduced in rats via injection of lipopolysaccharide (LPS) into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), CD11b and ionized calcium binding adaptor molecule (IBA)-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. RESULTS: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. CONCLUSION: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

MicroRNA-107 prevents amyloid-beta induced blood-brain barrier disruption and endothelial cell dysfunction by targeting Endophilin-1.

The disruption of blood-brain barrier (BBB) and endothelial cell dysfunction, associated with the cerebrovascular deposition of the amyloid-beta (Abeta) protein, have been characterized as the key pathological characteristics in Alzheimer's disease (AD). In various biologic processes of AD, researchers have proven that mircroRNAs (miRNAs) play critical roles. However, the role and function of miRNAs in the disruption of BBB of AD still remain unclear. Here, we found that mircroRNA-107 (miR-107) is endogenously expressed in human brain microvascular endothelial cells (ECs) of BBB model, while it is significantly down-regulated in ECs pre-incubated with Abeta. Abeta significantly impairs the integrity, increases the permeability of BBB, inhibits the viability of endothelial cells (ECs), and meanwhile down-regulates the expression of tight junction proteins ZO-1, Occludin and Claudin-5. Overexpression of miR-107 largely abrogated Abeta-induced disruption of BBB and endothelial cell dysfunction. Furthermore, overexpression of miR-107 also down-regulates endophilin-1, which is involved in the regulation of BBB permeability and the expression of ZO-1, Occludin, and Claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that Endophilin-1 was a direct and functional downstream target of miR-107. In conclusion, our results indicate that overexpression of miR-107 is able to prevent Abeta-induced blood-brain barrier disruption and endothelial cell dysfunction by targeting endophilin-1.

Different interventions for post-ischaemic stroke depression in different time periods: a single-blind randomized controlled trial with stratification by time after stroke.

OBJECTIVE: To determine the appropriate treatments for post-ischaemic stroke depression at different times after stroke. DESIGN: A single-blind, randomized, controlled trial that compared three intervention groups, with subgroups stratified by time after stroke. SETTING: Outpatient clinic. SUBJECTS: Eligible patients were recruited at discharge ( n = 73) and three ( n = 67), six ( n = 65), and nine months ( n = 69) after discharge, and patients completed mood questionnaires. INTERVENTIONS: Patients were randomly distributed into three groups: Group A received placebos and participated in general discussions; Group B, received citalopram and participated in general discussions; and Group C, received placebos and underwent cognitive behavioural therapy. All three groups participated in rehabilitation during three months of follow-up. MAIN MEASURES: Outcome was assessed three months after baseline using the 17-item Hamilton Depression Scale (HAMD17) and the Bech-Rafaelsen Melancholia Scale (MES). During treatment, the Udvalg for Kliniske Undersogelser side-effect scale was also administered. RESULTS: When stratification was not considered, the scores of Group B on the Melancholia Scale were lower than those of Group A ( P = 0.02); when the four time-based subgroups were analysed, significant differences were observed between Groups A and B (PMES = 0.02, PHAMD17 = 0.02) in the group recruited six months after discharge and between Groups A and C (PMES = 0.01) in the last time period nine months after discharge. CONCLUSIONS: The effects of citalopram or cognitive behavioural therapy is similar to the effect of rehabilitation alone for early-onset post-ischaemic depression; rehabilitation and citalopram for delayed-onset post-ischaemic depression; and rehabilitation and cognitive behavioural therapy for late-onset post-ischaemic depression are more effective than rehabilitation alone.

Impaired Frontolimbic Connectivity and Depressive Symptoms in Patients with Alzheimer's Disease.

BACKGROUND/AIMS: Depressive symptoms are commonly observed in Alzheimer's disease (AD). The underlying mechanisms of depressive symptoms in AD remain unclear; frontolimbic circuitry dysfunction may play a role. We aimed to investigate the microstructural integrity of frontolimbic connectivity of specific fiber tracts in AD patients with and without depressive symptoms using diffusion tensor imaging (DTI). METHODS: Eleven AD patients with depressive symptoms (dep-AD), 18 AD patients without depressive symptoms (nondep-AD), and 18 normal control (NC) subjects were included. The cingulum bundle (CB), uncinate fasciculus (UF), and fornix, mainly frontolimbic connectivity, were measured by DTI tractography and the metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were calculated. RESULTS: Compared with NC subjects, both dep-AD and nondep-AD patients showed significant differences for all indices in the fornix and significantly decreased FA and increased MD and RD in the bilateral CB and UF. When compared to nondep-AD patients, dep-AD patients showed significantly increased MD and RD in the bilateral CB and right UF. CONCLUSION: Depressive symptoms in AD patients may be involved in greater microstructural abnormalities of frontolimbic connectivity and myelin injury in the bilateral CB and right UF might contribute to the pathophysiology of depressive symptoms in AD.

Overexpression of Roundabout4 predicts poor prognosis of primary glioma patients via correlating with microvessel density.

Roundabout4 (Robo4), a new member of Robo proteins family, is specifically expressed in endothelial cells. Recent studies have indicated that Robo4 could regulate tumor angiogenesis and vascular permeability. However, the role and function of Robo4 are not well understood. This study was performed to investigate the expression of Robo4 in primary glioma patients, and thus to determine the association of Robo4 expression with microvessel density and survival of glioma patients. In this study, real-time PCR and immunohistochemistry were performed to examine the mRNA level and protein expression of Robo4 in both 43 cases of glioma samples and 10 cases of normal brain tissue samples. The results demonstrated that Robo4 was significantly up-regulated in glioma tissues compared with normal brain tissues. In addition, double immunofluorescent staining revealed that Robo4 expression co-localized with CD34 expression in the vessel of glioma tissues. The expression of Robo4 positively correlated with patients' age (P = 0.0139) and glioma grade (P < 0.0001). A linear correlation was observed between the relative mRNA expression of Robo4 values and corresponding microvessel density values (r = 0.9735, P < 0.0001). Kaplan-Meier analysis and log-rank test result showed that the overall survival of patients with Robo4 high expression was significantly shorter than that of patients with Robo4 low expression (P < 0.001). The results of present study verify that overexpression of Robo4 is related to poor prognosis of primary gliomas patients through correlating with microvessel density.

Disruption of thalamic connectivity in Alzheimer's disease: a diffusion tensor imaging study.

The aim of this study was to evaluate the structural integrity of the thalamic connectivity of specific fiber tracts in different stages of Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Thirty-five patients with AD and 22 normal control (NC) subjects were recruited. Based on Mini Mental State Examination score, the AD patients were divided into three subgroups for comparison with the NC group: mild (mi-AD, n = 14), moderate (mo-AD, n = 12), and severe (se-AD, n = 9) AD. The fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR) were selected to represent the thalamic connectivity with other brain regions. The fornix was divided into the column and body of the fornix (FX-1) and the bilateral fornix (crus)/stria terminalis (FX-2/ST) based on the atlas. Through the atlas-based analysis and fiber tracking method, we measured fractional anisotropy (FA), mean diffusivity (MD), and tract volume to reflect the microstructural and macrostructural changes of these fibers during AD progression. There were significant differences in the FA and MD of all fibers, except the right PTR, between the AD and NC subjects. Further subgroup analyses revealed that the mi-AD subgroup had decreased FA only in the FX-1 and increased MD in the FX-1 and bilateral ATR, the mo-AD subgroup showed declined FA and increased MD in the FX-1, bilateral FX-2/ST and ATR; the se-AD subgroup exhibited lower FA and higher MD values in all fibers except the right PTR. We also found reduced tract volume values in the FX and left ATR in the AD patients. Further subgroup analyses revealed that these differences only existed in the se-AD patients. Our DTI analyses indicate that the integrity of thalamic connectivity is progressively disrupted following cognitive decline in AD and that DTI parameters in the column and body of the fornix show promise as potential markers for the early diagnosis of AD and for monitoring disease progression.

Changes in the numbers of ribbon synapses and expression of RIBEYE in salicylate-induced tinnitus.

BACKGROUND: This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus. METHODS: C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons. RESULTS: The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7(th) d and decreased on the 9(th) and 10(th) d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days. CONCLUSION: This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus.

Correlation of fatigue during the acute stage of stroke with serum uric acid and glucose levels, depression, and disability.

BACKGROUND: To clarify the correlation of fatigue during the acute stage of stroke with serum uric acid (UA) and glucose levels, depression, and disability. DESIGN: Cross-sectional descriptive study. METHODS: A stroke group of 312 patients and a reference group of 312 healthy controls were recruited during the same period. Fatigue was assessed using the Fatigue Severity Scale (FSS). Patients with an FSS score ≥4 points were defined as having fatigue. Depression was assessed using the Self-rating Depression Scale (SDS). Patients with an SDS score ≥50 points were defined as having depression. Stroke severity and the level of disability were assessed with the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (MRS). RESULTS: The prevalence of fatigue in the stroke group was higher than that in the reference group (p < 0.001). Within the stroke group, low serum UA level, high MRS score, high serum glucose level, and high SDS score were associated with increased FSS score. The MRS score was associated most consistently with the FSS score (B = 0.411, 95% CI: 0.297, 0.525). Age, gender, chronic disease history, and NIHSS score were not associated with FSS score. CONCLUSIONS: Serum UA and glucose levels, depression, and disability are closely related to fatigue during the acute stage of ischaemic stroke.

Lower glomerular filtration rate after mild stroke induces cognitive impairment by causing endothelial dysfunction.

The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p < 0.001). At the three-month follow-up, a total of 150 (58.6%) patients had been diagnosed with PSCI. Multivariate logistic regression analysis showed that RHI was an independent factor affecting the occurrence of PSCI (p < 0.05). ROC curve showed that the area under the curve was 0.724, and the optimal cut-off value of RHI was 1.655, with the sensitivity and specificity for PSCI were 72.7% and 73.6%, respectively. The lower eGFRcys level after MIS was significantly associated with ED, and ED may mediate the higher incidence of PSCI at 3 months after MIS.

RBM3 enhances the stability of MEF2C mRNA and modulates blood-brain barrier permeability in AD microenvironment.

Blood-brain barrier (BBB) changes are acknowledged as early indicators of Alzheimer's disease (AD). The permeability and integrity of the BBB rely significantly on the essential role played by the tight junction proteins (TJPs) connecting endothelial cells. This study found the reduced RNA binding motif protein 3 (RBM3) expression in brain microvascular endothelial cells (BMECs) incubated with Aß1-42. This downregulation of RBM3 caused a decrease in the levels of ZO-1 and occludin and increased the permeability of BBB cell model in AD microenvironment. Myocyte enhancer factor 2C (MEF2C) expression was also inhibited in BMECs incubated with Aß1-42. A decrease in MEF2C expression led to increased permeability of BBB cell model in AD microenvironment and reductions in the levels of ZO-1 and occludin. Further analysis of the underlying mechanism revealed that RBM3 binds to and stabilizes MEF2C mRNA. MEF2C binds to the promoters of ZO-1 and occludin, enhancing their transcriptional activities and modulating BBB permeability. RBM3 increases the stability of MEF2C mRNA and subsequently modulates BBB permeability through the paracellular pathway of TJPs. This may provide new insights for AD research.