Brain-heart axis and the inflammatory response: connecting stroke and cardiac dysfunction.

In recent years, the mechanistic interaction between brain and heart has been explored in detail, which explains the effects of brain injuries on the heart and those of cardiac dysfunction on the brain. Brain injuries are the predominant cause of post-stroke deaths, and cardiac dysfunction is the second leading cause of mortality after stroke onset. Several studies have reported the association between brain injuries and cardiac dysfunction. Therefore, it is necessary to study the interaction between the brain and the heart to understand the underlying mechanisms of stroke and cardiac dysfunction. This review focuses on the mechanisms and the effects of cardiac dysfunction after the onset of stroke (ischaemic or haemorrhagic stroke). Moreover, the role of the site of stroke and the underlying mechanisms of the brain-heart axis after stroke onset, including the hypothalamic-pituitary-adrenal axis, inflammatory and immune responses, brain-multi-organ axis, are discussed.

Clinical Efficacy of Superficial Temporal Artery-middle Cerebral Artery Bypass Grafting Surgery Combined With Temporal Muscle Patch on Patients With Moyamoya Disease.

OBJECTIVE: To analyze the clinical efficacy of superficial temporal artery-middle cerebral artery (STA-MCA) bypass grafting surgery combined with temporal muscle patch and STA-MCA bypass grafting surgery alone on patients with moyamoya disease. METHODS: Totally 73 patients confirmed with moyamoya disease in our hospital between January 2019 and December 2021 were enrolled. Among them, 43 patients treated with STA-MCA bypass grafting surgery combined with temporal muscle patch were assigned to the experiment group, whereas 30 patients treated with STA-MCA bypass grafting surgery alone to the control group. The following items of the 2 groups were compared: clinical efficacy, total effective rate, and disease control rate 6 months after surgery, the changes of modified Rankin Scale (mRS) and Karnofsky performance scale (KPS) scores before and on the seventh day and 6 months after surgery, and changes of Glasgow coma scale scores before and 24 hours after surgery. In addition, the incidences of cerebral ischemia and cerebral hemorrhage within 1 year after surgery were counted. The cerebral perfusion-associated indexes including relative mean transit time (rMTT), relative time-to-peak, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV) on the seventh day and 6 months after surgery were compared between the 2 groups, and the predictive value of cerebral perfusion-associated indexes before surgery for clinical efficacy on patients was analyzed. RESULTS: The Glasgow coma scale score after surgery ( P >0.05) was similar between the 2 groups, but the clinical efficacy and total effective rate of the 2 groups were notably different (both P <0.05). Compared with those before surgery, mRS scores of both groups declined, whereas KPS scores increased (both P <0.05) on the seventh day after surgery. In addition, compared with those before surgery and on the seventh day after surgery, mRS scores of both groups decreased 6 months after surgery, whereas KPS scores increased (both P <0.05). Both the groups showed decreased rMTT and rTPP, and increased rCBF and rCBV on the seventh day after surgery than those before surgery (all P <0.05). In addition, both the groups still showed decreased rMTT and rTPP, and increased rCBF and rCBV 6 months after surgery than those before surgery and on the seventh day after surgery (all P <0.05). Most notably, the experimental group displayed improved cerebral perfusion-associated indexes than the control group 6 months after surgery (all P <0.05). The relief group showed notably higher rCBF and rCBV levels than the nonrelief group (both P <0.05). According to ROC analysis, the areas under the curves of rCBF and rCBV in forecasting the clinical efficacy on patients were 0.842 and 0.823, respectively. CONCLUSION: Superficial temporal artery-middle cerebral artery bypass grafting surgery combined with temporal muscle patch can deliver a higher total clinical curative rate for patients with moyamoya disease and can alleviate their coma.

Association between abnormal brain oscillations and cognitive performance in patients with bipolar disorder: Molecular mechanisms and clinical evidence.

Brain oscillations have gained great attention in neuroscience during recent decades as functional building blocks of cognitive-sensory processes. Research has shown that oscillations in "alpha," "beta," "gamma," "delta," and "theta" frequency windows are highly modified in brain pathology, including in patients with cognitive impairment like bipolar disorder (BD). The study of changes in brain oscillations can provide fundamental knowledge for exploring neurophysiological biomarkers in cognitive impairment. The present article reviews findings from the role and molecular basis of abnormal neural oscillation and synchronization in the symptoms of patients with BD. An overview of the results clearly demonstrates that, in cognitive-sensory processes, resting and evoked/event-related electroencephalogram (EEG) spectra in the delta, theta, alpha, beta, and gamma bands are abnormally changed in patients with BD showing psychotic features. Abnormal oscillations have been found to be associated with several neural dysfunctions and abnormalities contributing to BD, including abnormal GABAergic neurotransmission signaling, hippocampal cell discharge, abnormal hippocampal neurogenesis, impaired cadherin and synaptic contact-based cell adhesion processes, extended lateral ventricles, decreased prefrontal cortical gray matter, and decreased hippocampal volume. Mechanistically, impairment in calcium voltage-gated channel subunit alpha1 I, neurotrophic tyrosine receptor kinase proteins, genes involved in brain neurogenesis and synaptogenesis like WNT3 and ACTG2, genes involved in the cell adhesion process like CDH12 and DISC1, and gamma-aminobutyric acid (GABA) signaling have been reported as the main molecular contributors to the abnormalities in resting-state low-frequency oscillations in BD patients. Findings also showed the association of impaired synaptic connections and disrupted membrane potential with abnormal beta/gamma oscillatory activity in patients with BD. Of note, the synaptic GABA neurotransmitter has been found to be a fundamental requirement for the occurrence of long-distance synchronous gamma oscillations necessary for coordinating the activity of neural networks between various brain regions.

Hypertonic saline or mannitol for treating elevated intracranial pressure in traumatic brain injury: a meta-analysis of randomized controlled trials.

Hyperosmolar therapy is regarded as the mainstay for treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI). This still has been disputed as application of hypertonic saline (HS) or mannitol for treating patients with severe TBI. Thus, this meta-analysis was performed to further compare the advantages and disadvantages of mannitol with HS for treating elevated ICP after TBI. We conducted a systematic search on PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wan Fang Data, VIP Data, SinoMed, and China National Knowledge Infrastructure (CNKI) databases. Studies were included or not based on the quality assessment by the Jadad scale and selection criteria. Twelve RCTs with 438 patients were enrolled for the meta-analysis. The comparison of HS and mannitol indicated that they were close in field of improving function outcome (RR = 1.17, 95% CI 0.89 to 1.54, p = 0.258) and reducing intracranial pressure (MD = - 0.16, 95% CI: - 0.59 to 0.27, p = 0.473) and mortality (RR = 0.78, 95% CI 0.53 to 1.16, p = 0.216). The pooled relative risk of successful ICP control was 1.06 (95% CI: 1.00 to 1.13, p = 0.044), demonstrating that HS was more effective than mannitol in ICP management. Both serum sodium (WMD = 5.30, 95% CI: 4.37 to 6.22, p < 0.001) and osmolality (WMD = 3.03, 95% CI: 0.18 to 5.88, p = 0.037) were increased after injection of hypertonic saline. The results do not lend a specific recommendation to select hypertonic saline or mannitol as a first-line for the patients with elevated ICP caused by TBI. However, for the refractory intracranial hypertension, hypertonic saline seems to be preferred.

High-level expression and one-step purification of a soluble recombinant human interleukin-37b in Escherichia coli.

Interleukin (IL)-37 is a novel member of the IL-1 cytokine family. However, as a result of lacking efficient method to generate relatively large quantity of IL-37, little is known of its functions in man. In the present study, the recombinant human IL-37b containing a C-hexahistidine tag was expressed in Escherichia coli (E. coli). The expression level of IL-37b in E. coli was very high after induction with IPTG. Furthermore, IL-37b protein was largely found in the soluble fraction. The expressed protein was readily purified by one-step immobilized metal-ion affinity chromatography using Ni(2+)-nitrilotriacetic acid agarose. The purified IL-37b appeared as a single band on SDS-PAGE and the purity was more than 97%. The yield was 90mg IL-37b from 1l of bacterial culture. Western blotting and N-terminal sequencing confirmed the identity of the purified protein. The purified IL-37b inhibited significantly the release of tumor necrosis factor-α and IL-1ß in lipopolysaccharide-activated THP-1 cells. Thus, this method provides an efficient way to obtain an active IL-37 with high yield and high purity.

Behavioral features and disorganization of oscillatory activity in C57BL/6J mice after acute low dose MK-801 administration.

Low dose acute administration of N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 is widely used to model cognition impairments associated with schizophrenia (CIAS) in rodents. However, due to no unified standards for animal strain, dose, route of drug delivery, and the duration of administration, how different doses of MK-801 influence behavior and fundamental frequency bands of the local field potential (LFP) in cortical and subcortical brain regions without consistent conclusions. The optimal dose of MK-801 as a valid cognition impairers to model CIAS in C57BL/6J mice remains unclear. The current study characterizes the behavior and neural oscillation alterations induced by different low doses of MK-801 in medial prefrontal cortex (mPFC) and hippocampus CA1 of C57BL/6J mice. The results reveal that mice treated with 0.1 and 0.3 mg/kg MK-801 demonstrate increased locomotion and diminished prepulse inhibition (PPI), while not when treated with 0.05 mg/kg MK-801. We also find that MK-801 dose as low as 0.05 mg/kg can significantly diminishes spontaneous alteration during the Y-maze test. Additionally, the oscillation power in delta, theta, alpha, gamma and HFO bands of the LFP in mPFC and CA1 was potentiated by different dose levels of MK-801 administration. The current findings revealed that the observed sensitivity against spontaneous alteration impairment and neural oscillation at 0.05 mg/kg MK-801 suggest that 0.05 mg/kg will produce changes in CIAS-relevant behavior without overt changes in locomotion and sensorimotor processing in C57BL/6J mice.

A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas.

Most solid tumours are hypoxic. Tumour cell proliferation and metabolism accelerate oxygen consumption. The low oxygen supply due to vascular abnormalisation and the high oxygen demand of tumour cells give rise to an imbalance, resulting in tumour hypoxia. Hypoxia alters cellular behaviour and is associated with extracellular matrix remodelling, enhanced tumour migration, and metastatic behaviour. In light of the foregoing, more research on the progressive and prognostic impacts of hypoxia on gliomas are crucial. In this study, we analysed the expression levels of 75 hypoxia-related genes in gliomas and found that a total of 26 genes were differentially expressed in The Cancer Genome Atlas (TCGA) database samples. We also constructed protein-protein interaction networks using the STRING database and Cytoscape. We obtained a total of 10 Hub genes using the MCC algorithm screening in the cytoHubba plugin. A prognostic risk model with seven gene signatures (PSMB6, PSMD9, UBB, PSMD12, PSMB10, PSMA5, and PSMD14) was constructed based on the 10 Hub genes using LASSO-Cox regression analysis. The model was verified to be highly accurate using subject work characteristic curves. The seven-gene signatures were then analysed by univariate and multivariate Cox. Notably, PSMB10, PSMD12, UBB, PSMA5, and PSMB6 were found to be independent prognostic predictive markers for glioma. In addition, PSMB6, PSMA5, UBB, and PSMD12 were lowly expressed, while PSMB10 was highly expressed, in the TCGA and GTEx integrated glioma samples and normal samples, which were verified through protein expression levels in the Human Protein Atlas database. This study found the prognostic predictive values of the hypoxia-related genes PSMB10, PSMD12, UBB, PSMA5, and PSMB6 for glioma and provided ideas and entry points for the progress of hypoxia-related glioma.

Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage.

BACKGROUND: Oxidative stress and inflammation play important roles in the neuronal injury caused by intracerebral hemorrhage (ICH). Uric acid (UA), an important natural antioxidant, might reduce the neuronal injury caused by ICH. Delineating the relationship between UA and ICH will enhance our understanding of antioxidative mechanisms in recovery from ICH. METHODS: We conducted a retrospective study of 325 patients with acute supratentorial ICH to investigate the relationship between serum UA levels and hematoma volumes and prognosis. A hematoma volume of ≥30 mL was defined as a large hematoma. An unfavorable outcome was defined as a modified Rankin scale score of 4-6 on day 30. RESULTS: The serum UA level was significantly lower in the patients with a large hematoma volume (median, 306 µmol/L; 25th to 75th percentile, 243-411 µmol/L) than in those with a small hematoma volume (median, 357 µmol/L; 25th to 75th percentile, 271-442 µmol/L; P = 0.012). Similarly, the unfavorable outcome group had had lower serum UA levels (median, 309 vs. 363 µmol/L; P = 0.009) compared with the favorable outcome group. The results of the multivariate logistic analysis indicated that a lower serum UA level was associated with a larger hematoma volume (odds ratio, 0.996; P = 0.006) and an unfavorable outcome (odds ratio, 0.997; P = 0.030). CONCLUSIONS: The results from the present study have indicated that in patients with acute supratentorial ICH, a low serum UA level might indicate that the patient has a large hematoma volume and might be a risk factor for a poor day 30 functional prognosis.

Are they necessary? Preventive therapies for post-stroke depression: A meta-analysis of RCTs.

To explore the necessity and feasibility of early anti-depressive therapies in acute stroke patients, we conducted a meta-analysis of currently available randomized control studies (RCTs). Literature search in six databases was done with keywords of cerebrovascular accident, depression and prevention. Only RCTs that met the inclusion criteria were enrolled for further analysis. Twelve eligible studies were included in this meta-analysis. Prophylactic anti-depressive therapies following acute stroke were shown to reduce the incidence of depression in the patients (RR = =0.33, 95% CI: 0.25 to 0.43, p < 0.001), improve symptoms of depression (WMD: 5.73, 95% CI: 4.18 to 7.29, p < 0.001), improve motor function (WMD: 12.56, 95%CI: 9.07 to 16.04, p < 0.001) and neurological function (WMD: 1.13, 95%CI: 0.57 to 1.69, p < 0.001). However, anti-depressive therapies showed no effects on mortality (RR = 1.63, 95%CI: 0.55 to 4.85, p = 0.377) and adverse events incidence (RR = 0.93, 95%CI: 0.53 to 1.64, p = 0.806). Anti-depressive therapies following acute stroke is effective thus deserves to be advocated.

PKA-mediated phosphorylation of CREB and NMDA receptor 2B in the hippocampus of offspring rats is involved in transmission of mental disorders across a generation.

This study is aimed at the mechanism of transmission of mental disorders across a generation. We used 10 different stressors to establish an animal model of chronic unpredictable stress (CUS) before pregnancy. Forced swimming test (FST) and open field test (OFT) were used to analyze the behavior of 30-day-old adolescent offspring rats born to stress mothers. Magnetic resonance spectroscopy was used to measure glutamate, gamma-aminobutyric acid (GABA), and glutamine. Phosphate-activated glutaminase (PAG), glutamate decarboxylase (GAD), GABA-transaminase (GABA-T), protein kinase A (PKA), cAMP response element-binding protein (CREB), and N-methyl-D-aspartate (NMDA) receptor 2B (NR2B) were detected by western blot. Adolescent offspring rats in the CUS group exhibited depressive-like behavior in the FST and anxious behavior in the OFT. GAD was increased and GABA-T was decreased, which resulted in an increase in GABA levels and decrease of the glutamate/GABA ratio in the hippocampus of CUS offspring rats. Disruption of the glutamate/GABA-glutamine cycle was related to decrease PKA-mediated phosphorylation of CREB and NR2B in the hippocampus. These findings highlight the importance of mental health of females before pregnancy and suggest that CUS before pregnancy reduces p-CREB and p-NR2B in the offspring hippocampus, which could be responsible for behavioral disorders in the adolescent offspring.