Translational Neuroscience最新文献

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.

Introduction: Mitogen-activated protein kinase (MAPK) pathway is a major mechanism of acute brain damage in ischemic stroke. Pre-ischemic exercise is an effective method to reduce ischemic injury. However, the regulation by pre-ischemic exercise of MAPK pathway and associated mechanisms in animal models remains unclear.

Materials and methods: In this study, Male SD rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group, and exercise plus MCAO (EX + MCAO) group for 21 days, and then was established by MCAO. Longa score was used to measure neurological deficits at 0, 1, 2, and 3 days after MCAO. Hematoxylin and eosin staining was used to observe the brain injury. The expression of MAPK pathway was quantified by western blot. The M1 microglia protein was quantified by western blot and immunofluorescence, and the level of inflammatory factor was measured by enzyme-linked immunosorbent assay. TUNEL staining and western blot were used to measure apoptosis.

Results: In the current study, we observed that pre-ischemic exercise effectively decreased infarct volume, neurological deficit score and brain injury in MCAO rats through suppressing the activation of p-JNK and p-ERK1/2. Further investigation revealed that pre-ischemic exercise decreased M1 microglia activation and the serum level of TNF-α and IL-1β. In addition, the increased number of TUNEL-positive cells and Bax/Bcl-2 ratio also were reversed by pre-ischemic exercise.

Conclusions: Pre-ischemic exercise can alleviate inflammatory response and apoptosis by inhibiting the MAPK pathway in MCAO rats.

Objectives: Long-term isoflurane anesthesia exposure could result in postoperative cognitive dysfunction (POCD). Preoperative stress is also reported to be a risk factor of POCD. However, it is unknown whether acute stress could impair memory after long-term isoflurane anesthesia.

Methods: In this study, we categorized the mice with acute stress into mild (30 min restraint stress), moderate (60 min restraint stress), and severe (120 min restraint stress) stress groups and then we used Open-Field Test (OFT) to detect whether different scales of acute restraint stress successfully induced acute stress in mice. The memory performance of mice was measured using contextual and cued memory test, and the brain-derived neurotrophic factor protein levels of hippocampus was detected by Western blot.

Results: We verified that mild stress has pro-cognitive effect, but severe stress has amnestic effect. Moreover, we found that mild and moderate other than severe acute stress could partially attenuate the memory impairment induced by long-term isoflurane anesthesia.

Conclusion: Mild and moderate acute stress could partially attenuate the memory impairment induced by long-term isoflurane anesthesia.

Objective: The aim of this study is to determine the personal and clinical factors that can predict recovery of motor function in people with stroke.

Methods: Characteristics of the study participants such as age, sex, time since stroke and type of stroke, motor function, shoulder pain, amount and quality of use of the affected limb in the real world, wrist and elbow spasticity, handedness, central post-stroke pain and dose of massed practice were recorded. The data obtained were analyzed using descriptive statistics and multiple regression.

Results: A total of 144 patients with stroke with mean age, 58.71 ± 19.90 years participated in the study. The result showed that, the whole model significantly explained the total variance by 88.4%, F(14, 144) = 32.870, R ² = 0. 0.781, p < 0.001. However, in the final model, only four independent variables in the order of degree of predictability, amount of use of the limb in the real world (Beta = 0.455, p = 0.003), intensity of practice during rehabilitation session (Beta = 0.321, p < 0.001), wrist spasticity (Beta = 0.148, p = 0.004) and side affected (Beta = 0.093, p = 0.033) significantly predicted recovery of motor function.

Conclusion: Encouraging the use of the limb in the real world may be more important than practice during rehabilitation session in the clinic or in the laboratory.