Translational Neuroscience最新文献

Context: Accumulated evidence indicates that geniposide exhibits neuroprotective effects in ischemic stroke. However, the potential targets of geniposide remain unclear.

Objective: We explore the potential targets of geniposide in ischemic stroke.

Materials and methods: Adult male C57BL/6 mice were subjected to the middle cerebral artery occlusion (MCAO) model. Mice were randomly divided into five groups: Sham, MCAO, and geniposide-treated (i.p. twice daily for 3 days before MCAO) at doses of 25, 75, or 150 mg/kg. We first examined the neuroprotective effects of geniposide. Then, we further explored via biological information analysis and verified the underlying mechanism in vivo and in vitro.

Results: In the current study, geniposide had no toxicity at concentrations of up to 150 mg/kg. Compared with the MCAO group, the 150 mg/kg group of geniposide significantly (P < 0.05) improved neurological deficits, brain edema (79.00 ± 0.57% vs 82.28 ± 0.53%), and infarct volume (45.10 ± 0.24% vs 54.73 ± 2.87%) at 24 h after MCAO. Biological information analysis showed that the protective effect was closely related to the inflammatory response. Geniposide suppressed interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expression in the brain homogenate, as measured by enzyme-linked immunosorbent assay (ELISA). Geniposide upregulated A20 and downregulated TNF receptor-associated factor-6 and nuclear factor kappa-B phosphorylation in the MCAO model and lipopolysaccharide-treated BV2 cells at 100 μM.

Conclusions: Geniposide exhibited a neuroprotective effect via attenuating inflammatory response, as indicated by biological information analysis, in vivo and in vitro experiments, which may provide a potential direction for the application of geniposide in the treatment of ischemic stroke.

Objective: This research was conducted to discuss the recent prognosis of patients with acute cerebral infarction (ACI) combined with cerebral-cardiac syndrome (CCS).

Method: Eighty-seven patients with ACI were selected, which were divided into the ACI group (52 patients) and the CCS group (35 patients) according to whether the CCS was combined, and another 30 health controls were selected as the control group. Serum hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) levels of subjects in each group at the 1st day, the 3rd day, and the 7th day after admission were measured by enzyme-linked immunosorbent assay. After discharge for 30 days, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) score were utilized to evaluate the prognosis of patients. The role of serum HIF-1α and VEGF levels in the prognosis of ACI combined with CCS patients was assessed by receiver operating characteristic curve and the binary logistic regression analysis.

Results: Higher serum HIF-1α and VEGF levels were observed in the CCS and ACI groups versus the control group, and the levels of which were even higher in the CCS group in comparison to the ACI group. According to the prognosis of the NIHSS score, fasting blood glucose (FBG), Acute Physiology and Chronic Health Evaluation II score, creatine kinase-MB (CK-MB), and HIF-1α and VEGF levels at the 7th day of admission were higher while Glasgow coma scale (GCS) score was lower in the poor prognosis group than those in the good prognosis group, and the area under the curve (AUC) of serum HIF-1α and VEGF levels was 0.895 (95% confident interval [CI], 0.786-1.000), and 0.855 (95% CI, 0.731-0.980). According to the prognosis of the mRS score, FBG, CK-MB, and HIF-1α and VEGF levels at the 7th day of admission were higher while GCS score was lower in the poor prognosis group than those in the good prognosis group, and the AUC of serum HIF-1α and VEGF levels was 0.850 (95% CI, 0.722-0.979) and 0.901 (95% CI, 0.798-1.000). The results of the binary logistic regression analysis revealed that HIF-1α and VEGF levels may be independent risk factors influencing the prognosis of ACI combined with CCS.

Conclusion: Serum HIF-1α and VEGF have a good predictive value for assessing the recent prognosis of patients with ACI combined with CCS, which could be independent risk factors influencing the prognosis of disease.

Objectives: Studies have shown that arterial spin labeling (ASL) effectively replaces traditional MRI perfusion imaging for detecting cerebral blood flow (CBF) in patients with Moyamoya angiopathy (MMA). However, there are few reports on the relationship between neovascularization and cerebral perfusion in patients with MMA. The aim of this study is to investigate the effects of neovascularization on cerebral perfusion with MMA after bypass surgery.

Methods: We selected patients with MMA in the Department of Neurosurgery between September 2019 and August 2021 and enrolled them based on the inclusion and exclusion criteria. ASL imaging was used to monitor the baseline CBF level before surgery and determine the changes in cerebral vessels at postoperative 1 week and 6 months, respectively. The Alberta stroke grade, modified Rankin Scale (mRS), and digital subtraction angiography images were used to evaluate the effect of postoperative CBF status and prognosis. Ninety hemispheres from 51 patients were included in this study. There were no significant differences in the baseline data of the enrolled patients. At 1 week and 6 months post-surgery, the CBF state in the operation area was significantly changed compared with that at baseline (P < 0.05). The preoperative Alberta score (t = 2.714, P = 0.013) and preoperative mRS score (t = 6.678, P < 0.001) correlated with postoperative neovascularization.

Conclusion: ASL is an effective method for detecting CBF and plays an important role in the long-term follow-up of patients with MMA. Combined cerebral revascularization significantly improves CBF in the operation area both in the short and long terms. Patients with lower preoperative Alberta scores and higher mRS scores were more likely to benefit from combined cerebral revascularization surgery. However, regardless of the type of patient, CBF reconstruction can effectively improve prognosis.

Background: Cohen syndrome (OMIM No. # 216550) is a rare autosomal recessive disorder caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. Clinical manifestations include hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, and neutropenia. To date, more than 200 mutations of VPS13B have been reported in over 1,000 Cohen syndrome patients. This article reviews the clinical data of two cases of Cohen syndrome diagnosed by whole exome sequencing.

Results: Both children visited for psychomotor retardation. Gene detection showed a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and heterozygotic deletion of exon 3-19 of the VPS13B gene (Case 1), and a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and 8q22, NM_017890.4 Exon56 c10334_10335del in the VPS13B gene (Case 2). The variation was predicted to be pathogenic by related software, and they have not been reported.

Conclusion: Cohen syndrome should be considered in the differential diagnosis of any child with developmental retardation and neutropenia. The present study increases the mutation spectrum of the VPS13B gene and could be helpful in genetic diagnosis and genetic counseling in Cohen syndrome patients.

Background: Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoe^shl) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoe^shl mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoe^shl mice.

Results: Apoe^shl mice showed decreased motor skill learning and increased anxiety-like behavior toward heights. Apoe^shl mice did not show abnormal behavior in the Y-maze test, open-field test, light/dark transition test, and passive avoidance test.

Conclusion: Our findings suggest the utility of Apoe^shl mice in investigating the function of ApoE in the central nervous system.

Objective: MiRNAs play a key role in ischemic stroke (IS). Although miR-101-3p can participate in multiple disease processes, its role and mechanism in IS are not clear. The aim of the present study was to observe the effect of miR-101-3p activation on IS in young mice and the role of HDAC9 in this effect.

Methods: The young mice were first subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery, and the cerebral infarct area was assessed with 2,3,5-triphenyltetrazolium chloride staining. Meanwhile, the expressions of miR-101-3p and HDAC9 were tested using RT-qPCR or western blot. Besides, neuron morphology and apoptosis were confirmed using Nissl staining and TUNEL staining.

Results: We first verified that miR-101-3p was downregulated and HDAC9 was upregulated in the brain tissue of tMCAO young mice. Moreover, we proved that overexpression of miR-101-3p could improve cerebral infarction, neuronal morphology, and neuronal apoptosis in tMCAO young mice by lowering the expression of HDAC9.

Conclusions: Activation of miR-101-3p can protect against IS in young mice, and its mechanism is relevant to the inhibition of HDAC9. Therefore, miR-101-3p and HDAC9 might be the latent targets for IS therapy.

Background: Baicalin has been shown to promote spatial learning and neural regeneration, which might increase the differentiation of neural stem cells in Alzheimer's disease (AD) rat models. We aimed to study the role of baicalin on neuronal pentraxin-1 (NPTX-1), neuronal pentraxin-2 (NPTX-2), and C-reactive protein (CRP) in AD model rats.

Methods: The 30 male Sprague Dawley rats were divided into three groups: the control group, the AD model group, and the AD + baicalin group. Then, the Morris water maze was used to verify the effect of baicalin on the memory and spatial learning of rats. Immunohistochemistry and immunofluorescence were used to observe the expression of NPTX-1, NPTX-2, and CRP in brain tissue.

Results: Compared with the AD model group, the AD rats treated with baicalin spent significantly less time finding escape latencies (P = 0.008) and had longer cross-platform times in the target quadrant (P = 0.015). In addition, the AD + baicalin group had significantly higher numbers of hippocampal neurons compared with the AD model group (P < 0.05). Baicalin also obviously decreased the apoptosis of neurons. Moreover, compared with the AD model group, the NPTX-1 and CRP expression in the AD + baicalin group was significantly reduced (P = 0.000) while the expression of NPTX-2 in the brain tissue of AD rats was significantly increased (P = 0.000).

Conclusions: Baicalin can play a therapeutic role by downregulating NPTX-1, upregulating NPTX-2, and downregulating CPR in AD model rats.

Approximately 6.8 million people die annually because of problems related to the central nervous system (CNS), and out of them, approximately 1 million people are affected by neurodegenerative diseases that include Alzheimer's disease, multiple sclerosis, epilepsy, and Parkinson's disease. CNS problems are a primary concern because of the complexity of the brain. There are various drugs available to treat CNS disorders and overcome problems with toxicity, specificity, and delivery. Barriers like the blood-brain barrier (BBB) are a challenge, as they do not allow therapeutic drugs to cross and reach their target. Researchers have been searching for ways to allow drugs to pass through the BBB and reach the target sites. These problems highlight the need of nanotechnology to alter or manipulate various processes at the cellular level to achieve the desired attributes. Due to their nanosize, nanoparticles are able to pass through the BBB and are an effective alternative to drug administration and other approaches. Nanotechnology has the potential to improve treatment and diagnostic techniques for CNS disorders and facilitate effective drug transfer. With the aid of nanoengineering, drugs could be modified to perform functions like transference across the BBB, altering signaling pathways, targeting specific cells, effective gene transfer, and promoting regeneration and preservation of nerve cells. The involvement of a nanocarrier framework inside the delivery of several neurotherapeutic agents used in the treatment of neurological diseases is reviewed in this study.

Many diseases affect the autonomous nervous system and the central nervous system simultaneously, for example Parkinson's disease or irritable bowel syndrome. To study neurophysiologic interactions between the intestinal electrical activity and the electroencephalography (EEG) pattern of the brain, we combined intestinal electrical stimulation (IES) and non-invasive telemetric full-band DC EEG recordings in an acute pig-model. Intestinal motility was monitored with accelerometers. Brain activity was analyzed with regard to network driven phenomena like phase amplitude coupling (PAC) within two time-windows: 1 min after IES (early response) and 3 min after stimulation (late response). Here we present the results for two stimulation sites (small intestine, colon) and two parietal scalp-EEG channels (right and left somatosensory cortex region). Electrical stimulation consisted of a 30 or 130 Hz pulse. In summary, the PAC modulation index at a parietal EEG recording position is decreased after IES. This effect is in line with an inhibitory effect of our IES protocol regarding peristalsis. The surprisingly strong effects of IES on network driven EEG patterns may be translated into new therapeutic techniques and/or diagnostic tools in the future. Furthermore, analytic tools, operating on sparse datasets, may be ideally suited for the integration in implantable intestinal pacemakers as feedback system.