Association between advanced lung cancer inflammation index and all-cause and cardiovascular mortality among stroke patients: NHANES, 1999-2018.

Background: Stroke was a major global public health challenge, and its prognosis was remarkably associated with inflammation levels and nutritional status. The advanced lung cancer inflammation index (ALI) was a comprehensive indicator that combined inflammation and nutritional status. Currently, the relationship between ALI and the prognosis of stroke patients was not yet known. The purpose of the current study was to estimate their relationship. Methods: Cohort data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were collected. The association between ALI and all-cause and cardiovascular disease (CVD) mortality in stroke patients was estimated using a multivariable adjusted Cox model. Their non-linear relationship was analyzed by restricted cubic spline analysis. Sensitivity analysis was constructed through stratified analysis and interaction analysis. Results: 1,440 stroke patients were included in this study. An elevated ALI was significantly related to a reduced risk of all-cause mortality in stroke patients but not related to CVD mortality. A reverse J-shaped non-linear association between ALI and all-cause mortality in stroke patients, with an inflection point at 83.76 (the lowest of the mortality risk). On the left side of the inflection point, for each 10 U increase in ALI, there was a 16% reduction in the risk of all-cause mortality. However, on the right side, the risk increased by 6%. There was no remarkable interaction between stratified variables and ALI. Conclusion: This was the first study on the relationship between ALI and all-cause and CVD mortality in stroke patients. Elevated ALI was closely associated with a reduced risk of all-cause mortality. A reverse J-shaped non-linear relationship existed between the two, with an inflection point at 83.76. These findings implied that controlling the ALI of stroke patients within an appropriate range was crucial for their prognosis (such as weight management, albumin supplementation, anti-inflammatory treatment). The dynamic variation in ALI was also advantageous for clinicians in establishing personalized ALI criteria to maximize the long-term survival of stroke patients.

Migraine Duration as a Potential Amplifier of Obesity.

Purpose: Migraine is a complex neurovascular disorder with obesity as a notable risk factor. This study aimed to investigate an under-researched area of the association between migraine duration and body composition. Patients and Methods: Patients with migraine from a neurology outpatient department were enrolled and were categorized into four groups based on illness duration: 1 year, 1-5 years, 5-10 years, and >10 years. Patient demographics, blood biochemistry, and body composition data were collected and analyzed statistically. Results: Patients with migraine were predominantly female, with lower education levels, significant work stress, poor sleep, and limited exercise. Longer migraine duration corresponded to increased obesity metrics. Notably, those patients with under 1 year of illness showed elevated blood lipid and liver function levels, whereas those with >10 years showed increased weight, waist circumference, body mass index, and fat content, despite higher physical activity. Significant positive correlation between obesity metrics and migraine duration was seen in patients who had migraine for >1 year. Conclusion: Our findings indicate that protracted episodes of migraine could amplify obesity tendencies, underscoring the imperative of weight regulation in migraine intervention to diminish ensuing adiposity-associated hazards.

Examining the molecular mechanisms of topiramate in alleviating insulin resistance: A study on C2C12 myocytes and 3T3L-1 adipocytes.

PURPOSE: Migraine, a severely debilitating condition, may be effectively managed with topiramate, known for its migraine prevention and weight loss properties due to changes in body muscle and fat composition and improved insulin sensitivity. However, the mechanism of topiramate in modulating insulin response in adipocytes and myocytes remains elusive. This study aims to elucidate these molecular mechanisms, offering insights into its role in weight management for migraine sufferers and underpinning its clinical application. METHODS: Insulin resistance improvements were evaluated through glucose uptake measurements in C2C12 muscle cells and 3T3L-1 adipocytes, with Oil red O staining conducted on adipocytes. RNA-seq transcriptome analysis was used to identify the regulatory target genes of topiramate in these cells. The involvement of key genes and pathways was further validated through western blot analysis. RESULTS: Topiramate effectively reduced insulin resistance in C2C12 and 3T3L-1 cells. In C2C12 cells, it significantly lowered SORBS1 gene and protein levels. In 3T3L-1 cells, topiramate upregulated CTGF and downregulated MAPK8 and KPNA1 genes. Changes were notable in nuclear cytoplasmic transport and circadian signaling pathways. Furthermore, it caused downregulation of MKK7, pJNK1/ JNK1, BMAL1, and CLOCK proteins compared to the insulin-resistant model. CONCLUSION: This study provides preliminary insights into the mechanisms through which topiramate modulates insulin resistance in C2C12 myocytes and 3T3L-1 adipocytes, enhancing our understanding of its therapeutic potential in managing weight and insulin sensitivity in migraine patients.

Effect of magnesium sulfate on cerebral vasospasm in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Introduction: The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium sulfate on outcomes after aSAH, we conducted a systematic review and meta-analysis of relevant randomized controlled trials. Methods: PubMed, Embase, and the Cochrane Library were searched for relevant literature on magnesium sulfate for aSAH from database inception to March 20, 2023. The primary outcome was cerebral vasospasm (CV), and secondary outcomes included delayed cerebral ischemia (DCI), secondary cerebral infarction, rebleeding, neurological dysfunction, and mortality. Results: Of the 558 identified studies, 16 comprising 3,503 patients were eligible and included in the analysis. Compared with control groups (saline or standard treatment), significant differences were reported in outcomes of CV [odds ratio (OR) = 0.61, p = 0.04, 95% confidence interval (CI) (0.37-0.99)], DCI [OR = 0.57, p = 0.01, 95% CI (0.37-0.88)], secondary cerebral infarction [OR = 0.49, p = 0.01, 95% CI (0.27-0.87)] and neurological dysfunction [OR = 0.55, p = 0.04, 95% CI (0.32-0.96)] after magnesium sulfate administration, with no significant differences detected in mortality [OR = 0.92, p = 0.47, 95% CI (0.73-1.15)] and rebleeding [OR = 0.68, p = 0.55, 95% CI (0.19-2.40)] between the two groups. Conclusion: The superiority of magnesium sulfate over standard treatments for CV, DCI, secondary cerebral infarction, and neurological dysfunction in patients with aSAH was demonstrated. Further randomized trials are warranted to validate these findings with increased sample sizes.

Cervical and ocular vestibular evoked myogenic potentials in patients with Diabetic Peripheral Neuropathy.

BACKGROUND: Diabetes causes impaired microarterial blood flow, demyelination and neuronal damage, which may lead to cochlear damage and vestibular malfunction. Vestibular evoked myogenic potentials (VEMP) is a simple, reproducible test. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) can be explored in the saccadic-spinal and utriculo-ocular pathways in regular clinical practice. OBJECTIVE: To evaluate possible vestibular evoked myogenic potential (VEMP) abnormalities in patients with diabetic peripheral neuropathy. MATERIALS AND METHODS: 89 patients with Type 2 Diabetes in the present study consisted of three groups: 29 patients with no peripheral neuropathy (NDPN group), 26 patients with asymptomatic neuropathy (SDPN group), 34 patients with symptomatic neuropathy (DPN group). Meanwhile, 42 healthy subjects were recruited as controls. The clinical characteristics (including gender, age, body mass index (BMI), and illness duration), as well as lipids (including triglyceride (TG), cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)), uric acid, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) were compared among the four groups. Four groups were assessed using two vestibular tests including oVEMP and cVEMP. Latency and amplitude parameters were analyzed from VEMP plots. RESULTS: The latency of n10, p15 (oVEMP), p13, n23 (cVEMP) were significantly prolonged in the SDPN and DPN groups compared with the control and NDPN groups (p < 0.01), whereas latencies were similar in NDPN and the control groups. The amplitudes were not significantly different (p > 0.05). oVEMP latency p15 and cVEMP latency (p13, n23) were positively correlated with HbA1c, FBG, and illness duration, and oVEMP latency n10 was positively correlated with HbA1c and FBG. A nomogram, including FBG, HbA1C, HDL, TG, TC, LDL and group, was constructed to predict VEMP parameters and p13 was found to be independently associated with diabetic subgroups. Receiver operating characteristic curve (ROC) analysis showed good accuracy in predicting p13 in this nomogram. A user-friendly website has been created to facilitate the application of this prediction model ( https://fyey.shinyapps.io/VEMP_Model/ ). CONCLUSION: Patients with diabetic peripheral neuropathy may have vestibular dysfunction. VEMP may be useful in assessing vestibular impairment in diabetic patients.

Combined analysis of single-cell and bulk RNA sequencing reveals the expression patterns of circadian rhythm disruption in the immune microenvironment of Alzheimer's disease.

Background: Circadian rhythm disruption (CRD) represents a critical contributor to the pathogenesis of Alzheimer's disease (AD). Nonetheless, how CRD functions within the AD immune microenvironment remains to be illustrated. Methods: Circadian rhythm score (CRscore) was utilized to quantify the microenvironment status of circadian disruption in a single-cell RNA sequencing dataset derived from AD. Bulk transcriptome datasets from public repository were employed to validate the effectiveness and robustness of CRscore. A machine learning-based integrative model was applied for constructing a characteristic CRD signature, and RT-PCR analysis was employed to validate their expression levels. Results: We depicted the heterogeneity in B cells, CD4+ T cells, and CD8+ T cells based on the CRscore. Furthermore, we discovered that CRD might be strongly linked to the immunological and biological features of AD, as well as the pseudotime trajectories of major immune cell subtypes. Additionally, cell-cell interactions revealed that CRD was critical in the alternation of ligand-receptor pairs. Bulk sequencing analysis indicated that the CRscore was found to be a reliable predictive biomarker in AD patients. The characteristic CRD signature, which included 9 circadian-related genes (CRGs), was an independent risk factor that accurately predicted the onset of AD. Meanwhile, abnormal expression of several characteristic CRGs, including GLRX, MEF2C, PSMA5, NR4A1, SEC61G, RGS1, and CEBPB, was detected in neurons treated with Aß1-42 oligomer. Conclusion: Our study revealed CRD-based cell subtypes in the AD microenvironment at single-cell level and proposed a robust and promising CRD signature for AD diagnosis. A deeper knowledge of these mechanisms may provide novel possibilities for incorporating "circadian rhythm-based anti-dementia therapies" into the treatment protocols of individualized medicine.

Role of microglial metabolic reprogramming in Parkinson's disease.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Regression analysis of bleeding factors and the correlation between FPE and NLR after mechanical thrombectomy for acute anterior circulation large vessel occlusion.

Acute anterior circulation large vessel occlusion refers to a blockage in the blood flow of one of the major blood vessels in the anterior (front) part of the brain. Acute anterior circulation large vessel occlusion can lead to a range of symptoms, including sudden headache, difficulty speaking or understanding speech, weakness or numbness on one side of the body and loss of vision in one eye. According to relevant data, mechanical thrombectomy in the treatment of the large vessel recanalization rate can reach 70%. However, hemorrhage is one of the serious complications after mechanical thrombectomy, and it is the main factor leading to the deterioration of neurological function and death of patients after large blood vessels. Therefore, the risk factors of bleeding in patients were analyzed before surgery, and effective prevention during and after surgery had positive significance for patients undergoing mechanical thrombectomy. This study uses regression analysis to analyze the correlation between bleeding factors and FPE and NLR after mechanical thrombectomy for acute anterior circulation large vessel occlusion. We retrospectively analyzed 81 patients with acute anterior circulation large vessel occlusion who underwent mechanical embolization in our hospital from September 2019 to January 2022 and separated them into a bleeding group (46 patients) and a non-bleeding group (35 patients) based on the presence or absence of bleeding after surgery.

Recent research progress on metabolic syndrome and risk of Parkinson's disease.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Update on the application of mesenchymal stem cell-derived exosomes in the treatment of Parkinson's disease: A systematic review.

Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.

Effects of perioperative glycemic indicators on outcomes of endovascular treatment for vertebrobasilar artery occlusion.

Objective: Endovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT. Methods: We retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM). Results: A total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history. Conclusions: Admission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.

Prelimbic cortex miR-34a contributes to (2R,6R)-hydroxynorketamine-mediated antidepressant-relevant actions.

The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has recently been suggested to exert fast-acting antidepressant-relevant actions and was proposed as an ideal next-generation antidepressant. However, the microRNA-mediated mechanism underlying its effects is still unknown. In the present study, we investigated the role of miR-34a in the prelimbic (PL) cortex during (2R,6R)-HNK-mediated antidepressant-like effects. Male (8-10 weeks old) C57BL/6J mice and primary hippocampal cultured neurons were employed. The tests of forced swimming, tail suspension, sucrose preference, and female urine sniffing were used as indices of depressive-like behaviors. (2R,6R)-HNK enhanced miR-34a levels in a time-dependent manner at 1, 24 h, and 3 days in vitro, in a time-dependent manner at 1 and 24 h, and in a dose-dependent manner at 10 and 30 mg/kg in PL. Pretreatment with NBQX or verapamil blocked (2R,6R)-HNK-enhanced miR-34a expression and NBQX pretreatment blocked AMPA-elevated miR-34a levels in vitro. AAV-miR-34a in PL produced antidepression-behavioral effects and rescued stress-induced depressive-like behaviors. Moreover, PL AAV-miR-34a increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and potentiated evoked excitatory postsynaptic currents (EPSCs). Slices incubated with miR-34a mimic acutely enhanced the frequency and amplitude of mEPSCs in the PL. Intra-PL application of miR-34a rapidly produced antidepression-like effects and reversed stress-evoked depressive-like behaviors. Furthermore, intra-PL application of anti-miR-34a attenuated both systemic and local (2R,6R)-HNK-mediated antidepressant-like actions. Collectively, these results suggest that miR-34a in PL plays an antidepression-like role and contributes to the fast-acting antidepressant-relevant actions of (2R,6R)-HNK. The present study provides evidence for a miR-34a-dependent mechanism underlying the fast-acting antidepressant-like actions of (2R,6R)-HNK, indicating a novel role of PL miR-34a in antidepression.

LINC00473 protects against cerebral ischemia reperfusion injury via sponging miR-15b-5p and miR-15a-5p to regulate SRPK1 expression.

BACKGROUND: Cerebral ischemia is associated with a high burden of neurological disability. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) are crucial regulators in cerebral ischemia reperfusion (I/R) injury. Herein, we investigated the function and potential mechanism of long intergenic non-protein coding RNA 473 (LINC00473) in cerebral I/R injury. METHODS: We established oxygen glucose deprivation/reperfusion (OGD/R) model in Neuro-2a (N2a) cells to mimic the cerebral I/R injury in vitro. RT-qPCR and Western blot assays were conducted to detect target gene expression. Functional assays measured the effects of LINC00473 on cell viability, apoptosis and reactive oxygen species (ROS) production. A series of mechanism assays were carried out to detect the potential mechanism of LINC00473 in cerebral I/R injury. RESULTS: LINC00473 was significantly down-regulated in OGD/R-induced injury model. LINC00473 overexpression reversed the reduced cell viability as well as the enhanced apoptosis and ROS level induced by OGD/R. Moreover, LINC00473 functioneds as a competing endogenous RNA (ceRNA) to sponge miR-15b-5p and miR-15a-5p and thereby regulated SRSF protein kinase 1 (SRPK1) expression. CONCLUSIONS: Our findings confirmed the protective role of LINC00473 in cerebral I/R injury, which might provide a novel target for treating ischemic brain injury.

Phoenixin-20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs): A Protective Implication in Atherosclerosis.

The exact cause of atherosclerosis is not known, and therefore, the current treatment options are limited. The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) plays a key role in the initiation and progression of atherosclerosis. Phoenixin-20 is one of the newly identified neuropeptides with pleiotropic effects in the regulation of reproduction and other biological functions. G-protein receptor-coupled 173 (GPR173) is the putative receptor of Phoenixin-20. In the present study, we show that endothelial GPR173 is repressed upon ox-LDL stimulation in human aortic endothelial cells (HAECs). We further elaborate on the hypothesis that GPR173 could be involved in the pathogenesis of atherosclerosis through a series of experiments. Our results indicate that ox-LDL remarkably triggers the increase of ROS, NOX-4, pro-inflammatory cytokines IL-1ß, IL-8, and MCP-1 expression, as well as adhesion molecules ICAM-1 and VCAM-1 release. However, the agonism of GPR173 using Phoenixin-20 significantly ameliorates all of these harmful effects from ox-LDL by suppressing the NF-κB pathway. Furthermore, we show that agonism of GPR173 by Phoenixin-20 prevents the attachment of monocytes THP-1 to endothelial cells, which is an important therapeutic approach to preventing atherogenesis. In conclusion, our study demonstrates that GPR173 agonism by Phoenixin-20 plays a protective role against ox-LDL-induced endothelial dysfunction, implying that Phoenixin-20 may have therapeutic implications in atherosclerosis.

Effect of matrine on JAK2/STAT3 signaling pathway and brain protection in rats with cerebral ischemia-reperfusion.

BACKGROUND: Ischemic encephalopathy is a common clinical disease. The main treatment goal is to achieve vascular recanalization. However, after vascular recanalization, the reperfusion of fresh blood can change local cell metabolism, thus adversely affecting cell structure and function, which can result in reperfusion injury. OBJECTIVES: To explore the effect of matrine intervention of different concentrations on JAK2/STAT3 signaling pathway and brain protection in rats with cerebral ischemia-reperfusion. MATERIAL AND METHODS: Healthy male Sprague Dawley rats were divided into a blank control group (20 rats), a model group (80 rats) and a sham group (20 rats). In the model group, the middle cerebral artery was occluded with suture method to establish cerebral ischemia-reperfusion model rats, which were subdivided into cerebral ischemia-reperfusion group, and 5, 10 and 20 mg/kg matrine groups, with 20 rats in each group. Indicators including neurological function score, brain infarct size, brain water content, lactic dehydrogenase activity, protein expressions of p-JAK2 and p-STAT3, as well as superoxide dismutase activity and malondialdehyde content were evaluated. RESULTS: Compared with cerebral ischemia-reperfusion group, all the indicators were significantly improved in the 3 matrine treatment groups in a dose-dependent manner, and protein expressions of p-JAK2 and p-STAT3 in the brain tissue and brain cell apoptosis rate were decreased with the increase of matrine concentration (all p < 0.05). CONCLUSIONS: Matrine can significantly ameliorate the neurological function and brain edema of rats with cerebral ischemia-reperfusion, and improve superoxide dismutase, malondialdehyde and lactic dehydrogenase levels in the brain tissue and brain cell apoptosis rate. The mechanism of matrine may be related to the inhibition of abnormal JAK2/STAT3 signaling pathway activation.

Neuropsychological and neuroimaging assessments of early cognitive impairment in patients after mild ischemic stroke and transient ischemic attack.

This study aimed to identify markers of early cognitive impairment after acute mild ischemic cerebrovascular disease. To further explore the relationship between neuroimaging markers of vascular and neurodegenerative injuries and post-stroke cognitive impairment, 86 patients with transient ischemic attack/acute mild ischemic stroke were recruited. Demographic information, clinical data, stroke scale scores (Modified Rankin Scale, National Institutes of Health Stroke Scale), and neuroimaging parameters (medial temporal lobe atrophy, global cortical atrophy, white matter hyperintensities, location and number of acute infarcts) were collected. All participants underwent neuropsychological evaluation at the time of discharge. The neurocognitive assessment was conducted using the Montreal Cognitive Assessment-Basic and Trail-Making Test A. It was found that low Montreal Cognitive Assessment-Basic scores were associated with global cortical atrophy and lower education levels. The completion time on the Trail-Making Test A was significantly correlated with medial temporal lobe atrophy and less education. It is concluded that global cortical atrophy and lower education levels can be used as rapid indicators of early cognitive impairment in patients after a transient ischemic attack and acute mild ischemic stroke. Medial temporal lobe atrophy also appears to be associated with mental processing speed in patients after a transient ischemic attack and acute mild ischemic stroke.

Decreased Glutamatergic Synaptic Strength in the Periaqueductal Gray Contributes to Maintenance of Visceral Pain in Male Rats with Experimental Pancreatitis.

Visceral pain originating from chronic inflammation of the pancreas is often intractable and difficult to manage clinically. However, the pathogenesis of the central nervous system underlying visceral pain is still poorly understood. The aim of the present study was to investigate the role of the midbrain ventrolateral periaqueductal gray (vlPAG) in a rat model of chronic visceral pain induced by pancreatitis. In the present study, we used a well-established rat model of chronic pancreatitis induced by tail vein injection of dibutyltin dichloride (DBTC). To assess the DBTC-induced visceral pain, we examined the abdominal withdrawal by von Frey filament test. We further studied the synaptic transmission in the vlPAG by whole-cell patch-clamp electrophysiological recordings. Rats receiving DBTC injection exhibited a significantly increased withdrawal frequency to mechanical stimulation of the abdomen compared to rats injected with vehicle. Interestingly, compared to rats injected with vehicle, we found that neurons dissected from DBTC-treated rats exhibited a significantly decreased synaptic strength, which was revealed by a diminishedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartic acid (AMPA/NMDA) ratio in the vlPAG. Moreover, our results further demonstrated that neurons obtained from DBTC-treated rats displayed a higher paired-pulse ratio, as well as less frequent and smaller amplitudes of miniature excitatory postsynaptic currents in the vlPAG compared to rats injected with vehicle. Furthermore, intra-vlPAG microinjection of AMPA alleviated DBTC-induced abdominal hypersensitivity. Taken together, our findings suggest that diminished glutamatergic synaptic strength via both presynaptic and postsynaptic mechanisms in the midbrain vlPAG is associated with DBTC-induced abdominal hypersensitivity. In addition, activation of AMPA receptors in the vlPAG alleviates DBTC-induced abdominal hypersensitivity.

Ketamine metabolite (2R,6R)-hydroxynorketamine enhances aggression via periaqueductal gray glutamatergic transmission.

(2R,6R)-hydroxynorketamine (HNK), a metabolite of ketamine, has recently been suggested to be a potent antidepressant for treating animal depression and has rapid-onset and long-lasting action through potentiating glutamatergic transmission. However, its other effects are still unclear. In the present study, we tested the effects of (2R,6R)-HNK on offensive aggression. A resident-intruder (RI) test was used as the main model to test elements of offensive aggression, including threats and bites. Electrophysiological recordings in the ventrolateral periaqueductal gray (vlPAG) were used to measure the functions of glutamatergic synaptic transmission. A single systemic injection of (2R,6R)-HNK, but not (2S,6S)-HNK, increased elements of offensive aggression, including threats and bites, in a dose-dependent manner with long-lasting action. Moreover, (2R,6R)-HNK increased the input-output curve, the AMPA-mediated current, and the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and decreased the paired-pulse ratio (PPR) in the vlPAG. Furthermore, intra-vlPAG application of (2R,6R)-HNK increased aggressive and biting behaviors, which were abolished by an intra-vlPAG pretreatment with the AMPA receptors antagonist, CNQX. Notably, the intra-vlPAG CNQX pretreatment eliminated systemic (2R,6R)-HNK-enhanced aggressive and biting behaviors. The results of this suggest that (2R,6R)-HNK evokes offensive aggression by increasing vlPAG glutamatergic transmission. Although (2R,6R)-HNK is currently suggested to be effective for treating depression, its side effect of increasing offensive aggression should be a subject of concern in future drug development and therapy.

The impact of chronic intermittent hypoxia on the expression of intercellular cell adhesion molecule-1 and vascular endothelial growth factor in the ischemia-reperfusion rat model.

The aim of this study was to investigate the effect and mechanism of chronic intermittent hypoxia (CIH) on cerebral injury using the ischemia-reperfusion rat model. In total, 36 SD rats were divided into three groups: pseudo-surgery group (sham group), ischemia-reperfusion (IR) group (CIR group), and CIH intervention group (CIH group). The IR model was established using the suture-occluded method. CIH intervention was performed starting at 12 weeks prior to the establishment of the IR model for rats in the CIH group. Ultra-microstructure was examined using an electron microscope. Expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) in rat brain tissue was evaluated by immunohistochemical methods and western blot assays. The neurological deficit scores of rats in the CIH group were higher than those in the CIR group (p < 0.05). Using electron microscopy, we observed more severe edema around the capillaries of the rat brain that resulted in more pressure on the vascular wall of the capillaries in the CIH group compared to the CIR group. The expression of ICAM-1 and VEGF in rat brain tissue was rare in the sham group, but was significantly elevated in the CIR group (p < 0.05) and even higher in the CIH group, compared to the CIR group. Hence, the brain injury in ischemia-reperfusion rat models following CIH intervention may be related to the increased expression of ICAM-1 and VEGF.

Reduction of the systemic inflammatory induced by acute cerebral infarction through ultra-early thrombolytic therapy.

Acute ischemic stroke induces systemic inflammation, exhibited as changes in body temperature, white blood cell counts and C-reactive protein (CRP) levels. The aim of the present study was to observe the effects of intravenous thrombolytic therapy on inflammatory indices in order to investigate the hypothesis that post-stroke systemic inflammatory response occurs in response to the necrosis of brain tissues. In this study, 62 patients with acute cerebral infarction and indications for intravenous thrombolysis were divided into three groups on the basis of their treatment and response: Successful thrombolysis (n=36), failed thrombolysis (n=12) and control (n=14) groups. The body temperature, white blood cell counts and high-sensitivity (hs)-CRP levels were recorded pre-treatment and on post-stroke days 1, 3, 5 and 7. Spearman's correlation analysis showed that the pre-treatment National Institutes of Health Stroke Scale (NIHSS) score positively correlated with body temperature, white blood cell count and hs-CRP levels. On day 3 of effective intravenous thrombolysis, the body temperature and white blood cell were decreased and on days 3 and 5, the serum levels of hs-CRP were reduced compared with those in the failed thrombolysis and control groups. The results indicate that the systemic inflammatory response following acute cerebral infarction was mainly caused by ischemic injury of local brain tissue; the more serious the stroke, the stronger the inflammatory response. Ultra-early thrombolytic therapy may inhibit the necrosis of brain tissue and thereby reduce the inflammatory response.