Journal of Neuroscience Research最新文献

Microcirculatory disturbances may play an important role in futile recanalization. This study investigated the early factors affecting the prognosis of cerebral infarction in rats and whether low-molecular-weight heparin improves microcirculation disorders. We used a male rat middle cerebral artery occlusion (MCAO) model with 90 min transient MCAO (tMCAO) or permanent MCAO (pMCAO) ischemia, and analyzed after 24 h. Cortical blood flow was monitored using laser speckle blood flow imaging. Furthermore, 1.5 mg/kg Enoxaparin (Enox) was administered 30 min before ischemia or 1 h post-reperfusion. The tMCAO group received saline. Our results showed that the proportion of moderate and severe (M&S) injuries was 54.2% in tMCAO rats, 100% in pMCAO rats, and reduced to 25% in the enoxaparin pre-ischemic (Enox-pre) group. The reperfusion rats had persistent hypoperfusion and the lowest blood flow after 1 h post-reperfusion. The 1 and 24 h post-reperfusion cortical blood flow was negatively correlated with infarct volume and neurological scores. The Enox-pre group had higher blood flow than the tMCAO group at 1 h post-reperfusion (p < 0.05). Enox-pre reduced fibrin deposition after 1 h post-reperfusion (p < 0.01), improved microvascular patency after 1 and 24 h (p < 0.01), and decreased Evans blue leakage after 24 h (p < 0.001). We concluded that 50% of the futile recanalization rate also exists in rats with recanalization 1.5 h post-infarction. The degree of reperfusion blood flow recovery significantly affects cerebral infarction outcomes. Enox-pre reduces the proportion of poor outcomes by reducing early microthrombus formation, enhancing microcirculation, increasing reperfusion blood flow, and mitigating blood–brain barrier (BBB) disruption.

Melatonin and its receptors play a primary role in regulating circadian rhythms, which are frequently disrupted in patients with Alzheimer's disease (AD). Furthermore, there is increasing evidence that the use of a ketogenic diet (KD) delays the onset of AD. Therefore, we aimed to investigate whether KD has an ameliorative effect on AD through the regulation of melatonin receptors. In this study, male Sprague–Dawley rats were divided into three groups: sham, AD, and KD. At the end of KD supplementation, behavioral parameters were determined by the Morris Water Maze. Melatonin levels, protein expression levels, and immunoreactivity of MT1–MT2 in thehippocampus and striatum were determined by ELISA, Western blotting, and immunofluorescence staining, respectively. As a result, KD improved memory decline in AD rats. Also, KD increased melatonin levels in the hippocampus but did not affect striatum melatonin levels. MT1 expression tended to increase in the hippocampus of the AD group, while MT2 expression decreased. On the contrary, KD treatment increased both MT1 and MT2 expressions. In the striatum, there was no change in MT1 expression in the AD and KD groups, but MT2 expression increased in the AD group compared with the sham group and was suppressed in the KD group. In addition, KD treatment reduced streptozotocin-induced apoptosis and neuroinflammation in the hippocampus and striatum. Our results suggest that KD may improve AD-associated inflammation and apoptosis by altering melatonin levels and the expression of MT2 receptors in the hippocampus and striatum. Therefore, KD may be a promising preventive and therapeutic option for AD.

Ischemic stroke (IS) is a prevalent and serious neurological disorder, and is one of the major contributors to mortality and disability worldwide. The activation of autophagy and the inflammatory response following cerebral ischemia are crucial in the progression of IS. Protein phosphatase 1 regulatory subunit 15A (PPP1R15A), as a stress-responsive protein, has been proven to be closely associated with autophagy. Nevertheless, the molecular mechanism of PPP1R15A in IS remains to be fully understood. Our study screened PPP1R15A as a candidate gene by bioinformatics analysis of the differentially expressed genes (DEGs) in IS and autophagy-related genes (ARGs). Functionally, experiments uncovered that down-regulation of PPP1R15A alleviated oxygen–glucose deprivation/reoxygenation (OGD/R)-mediated inhibition of cell viability and promotion of LDH release, cell apoptosis, autophagy, and inflammation in A172 and SH-SY5Y cells. Simultaneously, silencing PPP1R15A ameliorated the IS progression in the middle cerebral artery occlusion and reperfusion (MCAO/R) rat model. Furthermore, PPP1R15A activated the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway in vivo and in vitro. Rescue experiments indicated that TLR4 inhibitors TAK-242 and NF-κB inhibitors BAY-11-7082 effectively alleviated the malignant progression of IS mediated by overexpression of PPP1R15A. Our data illustrated that PPP1R15A promoted OGD/R-induced cytotoxicity, apoptosis, autophagy, and inflammation by activating the TLR4/NF-κB pathway.

Among all upper extremity nerves, the ulnar nerve is both the most commonly injured and notoriously difficult to regenerate. Despite this, ulnar nerve injuries remain understudied. Nonhuman primates (NHPs) offer an ideal model for the human upper extremity, but existing NHP nerve trauma literature is biased towards median and radial injury models. To address this, a nonhuman primate ulnar nerve injury model was developed and regeneration assessed following sural nerve autografting using electrophysiological and histological techniques. Unilateral 4 cm ulnar nerve injuries were created at the mid-forearm level, sural nerve autografts were sutured into resulting defects (n = 3), and animals were survived for 6 months. At the terminal time point, intraoperative electrophysiological testing, tissue harvest, and tissue processing were performed. Naïve nerves (n = 5) served as controls. Animals appeared clinically normal throughout the study period, other than an expected decrease in fine hand muscle function. After 6 months, histological and electrophysiological evidence suggested that axons crossed the graft and reached distal muscle targets. However, regenerating nerves exhibited a reduced motor nerve conduction velocity, reduced compound action muscle potential (CMAP) amplitude and area under the curve, increased latency, and increased duration versus naïve controls as expected. Histological analysis revealed reduced axon diameters, thinner myelin sheaths, and smaller muscle fiber cross-sectional areas as compared to controls. At 6 months post-injury, 4 cm ulnar defects bridged with sural autografts show signs of ongoing regeneration and nascent reinnervation. Specific electrophysiological and histological benchmarks for ulnar nerve recovery following clinically relevant autografting are presented.

Schwann cells and satellite glial cells (SGCs) are important peripheral glial cells in the dorsal root ganglion (DRG) and commendable participants in regulating neuronal functions. Herein, through re-analysis of publicly available single-nucleus RNA sequencing data from naïve and injured DRG at 1 and 3 days following sciatic nerve crush, we systematically characterized the transcriptomic alterations in Schwann cells and SGCs. Cell clustering and counting showed that peripheral glial cells occupied a large population after sciatic nerve crush injury. Using differentially expression analysis, we found that apoptosis and immune responses were involved in all these examined peripheral glial cells. Unique glial cells also responded differently to sciatic nerve crush injury, with myelinating Schwann cells characterized by enriched adenosine 5′-monophosphate activated protein kinase (AMPK) metabolic signaling, non-myelinating Schwann cells characterized by enriched tissue-remodeling-related signaling, and SGCs characterized by enriched ion channels. Using single-cell regulatory network inference and clustering (SCENIC) to determine essential transcription factors in specific cell type at the naïve state and at multiple time points after sciatic nerve crush injury, we found that Schwann cells and SGCs possessed their own elevated transcription factor-coding genes, with activating factor 3 (Atf3) commonly highly up-regulated in all peripheral glial cells. This study provides a profiling map of peripheral glial cells at the naïve and injured states, expands the acknowledgment of the molecular background of nerve injury, and can lead to novel strategies to promote sensory nerve regeneration.

Piano training enables the study of the interplay between the auditory and motor domains in the acquisition of complex skill. Here, we uniquely combine longitudinal and cross-sectional designs to show how the motor and auditory brain systems respond in novice pianists over a 6-month training period. In the auditory domain, we found no differences in brain activation between novice pianists and a passive control group. In a specially designed piano task on an MRI-compatible keyboard, we demonstrate that the time course of neuroplastic reorganization in the cortical and subcortical regions reflects the shift from spatial attention to automated movements, but depends on task demands related to bimanual coordination. Importantly, no single model of brain plasticity can fully explain the observed dynamic time courses of functional changes. Finally, we demonstrate that the increased activation in the dorsal premotor and parietal cortices in novice pianists compared to skilled musicians while performing the motor task vanishes within the first 6 months of training. These results present converging evidence that the dynamic musical-training-related plasticity is highly contextual, and underscore the importance of ecological designs in research on skill acquisition.