Translatome and transcriptome profiling of neonatal mice hippocampus exposed to sevoflurane anesthesia.

Exposure to anesthesia in early life may cause severe damage to the brain and lead to cognitive impairment. The underlying mechanisms, which have only been investigated in a limited scale, remains largely elusive. We performed translatome and transcriptome sequencing together for the first time in hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5 % sevoflurane for 2 h on day 6, 7, 8, 9 and treated another group on day 6, 7. We performed behavioral study after day 30 for both groups and the control to evaluate the cognitive impairment. On day 36, we collected translatome and transcriptome from the hippocampus in the two groups, compared the gene expression levels between the groups and the control, and validated the results with RT-qPCR. We identified 1750 differentially expressed genes (DEGs) from translatome comparison and 1109 DEGs from transcriptome comparison. As expected, translatome-based DEGs significantly overlapped with transcriptome-based DEGs, and functional enrichment analysis generated similar enriched cognition-related GO terms and KEGG pathways. However, for many genes like Hspa5, their alterations in translatome differed remarkably from those in transcriptome, and Western blot results were largely concordant with the former, suggesting that translational regulation plays a significant role in cellular response to sevoflurane. Our study revealed global alterations in translatome and transcriptome of mice hippocampus after neonatal exposure to sevoflurane anesthesia and highlighted the importance of translatome analysis in understanding the mechanisms responsible for anesthesia-induced cognitive impairment.

Knockdown of XIST Attenuates Cerebral Ischemia/Reperfusion Injury Through Regulation of miR-362/ROCK2 Axis.

Long non-coding RNAs (lncRNAs) are considered as critical regulators in the pathogenesis of cerebral ischemia. In this present study, we aimed to investigate the impact and underlying mechanism of lncRNA X-inactive specific transcript (XIST) in cerebral ischemia/reperfusion (I/R) injury. An oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12 cells was applied to mimic cerebral I/R injury in vitro and middle cerebral artery occlusion/reperfusion (MCAO/R) model was performed in mice to mimic cerebral I/R injury in vivo. Real-time PCR, fluorescence in situ hybridization (FISH) assay, and western blotting assay were carried out to detect the expression levels of XIST, miR-362, and Rho-related coiled-coil containing protein kinase 2 (ROCK2). The functional experiments were measured by CCK-8 assay, immumofluorescence assay, ELISA assay, TUNEL, and TTC staining. Results displayed that XIST was elevated in PC12 cells with OGD/R, as well as in the ischemic penumbra of mice with MCAO/R. In vitro, knockdown of XIST facilitated cell survival, inhibited apoptosis, and alleviated inflammation injury in OGDR PC12 cells. In vivo, inhibition of XIST remarkably reduced the neurological impairments, promoted neuron proliferation, and suppressed apoptosis in MCAO mice. Mechanistically, XIST acted as a competing endogenous RNA of miR-362 to regulate the downstream gene ROCK2. In conclusion, depletion of XIST attenuated I/R-induced neurological impairment and inflammatory response via the miR-362/ROCK2 axis. These findings offer a potential novel strategy for ischemic stroke therapy.

Clinical features of and risk factors for intracranial aneurysms associated with moyamoya disease.

BACKGROUND: The clinical features of aneurysms associated with moyamoya disease (MMD) and risk factors for the formation and rupture of aneurysms are not well defined. AIMS: In this study, we retrospectively analyzed clinical data of MMD patients and examined the potential risk factors for the formation and rupture of aneurysms in these patients. METHODS: The medical records of all MMD patients in our hospital from April 2012 to May 2019 were reviewed. The logistic regression analysis was used to determine the independent association between various potential risk factors and the presence or rupture of intracranial aneurysms in MMD patients. RESULTS: Of 2230 MMD patients, 182 (8.2%) cases had intracranial aneurysms. The mean age of onset in patients with aneurysms was 47.2 years, which was significantly higher when compared with those without aneurysms (p < 0.001). In logistic regression analysis, age of onset remained significantly associated with the presence of intracranial aneurysms, while female gender, hypertension, diabetes mellitus, and coronary artery disease were not. Besides, intracranial aneurysms were significantly associated with intracranial hemorrhage in MMD patients (odds ratio [OR] = 5.19; 95% confidence interval [CI], 3.80-7.09). About 60% aneurysms >5 mm in size, and 62.1% aneurysms with irregularly shaped morphology were ruptured. Aneurysms located in basilar tip, collateral or moyamoya vessels were more likely to present with rupture. CONCLUSIONS: Age was an important risk factor for intracranial aneurysms formation in MMD patients. Aneurysms increased the risk of intracerebral hemorrhage in MMD patients, and their ruptures were correlated with aneurysms size, location, and morphology.

Dopaminergic neuron injury in Parkinson's disease is mitigated by interfering lncRNA SNHG14 expression to regulate the miR-133b/ α-synuclein pathway.

This study explored the influence of long non-coding RNA (lncRNA) SNHG14 on α-synuclein (α-syn) expression and Parkinson's disease (PD) pathogenesis. Firstly, we found that the expression level of SNHG14 was elevated in brain tissues of PD mice. In MN9D cells, the rotenone treatment (1µmol/L) enhanced the binding between transcriptional factor SP-1 and SNHG14 promoter, thus promoting SNHG14 expression. Interference of SNHG14 ameliorated the DA neuron injury induced by rotenone. Next, we found an interaction between SNHG14 and miR-133b. Further study showed that miR-133b down-regulated α-syn expression by targeting its 3'-UTR of mRNA and SNHG14 could reverse the negative effect of miR-133b on α-syn expression. Interference of SNHG14 reduced rotenone-induced DA neuron damage through miR-133b in MN9D cells and α-syn was responsible for the protective effect of miR-133b. Similarly, interference of SNHG14 mitigated neuron injury in PD mouse model. All in all, silence of SNHG14 mitigates dopaminergic neuron injury by down-regulating α-syn via targeting miR-133b, which contributes to improving PD.

Neurophysiological Differences between Flail Arm Syndrome and Amyotrophic Lateral Sclerosis.

There are many clinical features of flail arm syndrome (FAS) that are different from amyotrophic lateral sclerosis (ALS), suggesting they are probably different entities. Studies on electrophysiological differences between them are limited at present, and still inconclusive. Therefore, we aimed to find clinical and neurophysiological differences between FAS and ALS. Eighteen healthy control subjects, six FAS patients and forty-one ALS patients were recruited. The upper motor neuron signs (UMNS), split-hand index (SI), resting motor threshold (RMT), central motor conduction time (CMCT) were evaluated and compared. There was no obvious upper motor neuron signs in FAS. The SI and RMT level in FAS was similar to control subjects, but significantly lower than that of in ALS. Compared with control group, the RMT and SI in ALS group were both significantly increased to higher level. However, no significant difference of CMCT was found between any two of these three groups. The differences in clinical and neurophysiological findings between FAS and ALS, argue against they are the same disease entity. Since there was no obvious UMNS, no split-hand phenomenon, and no obvious changes of RMT and CMCT in FAS patients, the development of FAS might be probably not originated from motor cortex.

bFGF promotes the differentiation and effectiveness of human bone marrow mesenchymal stem cells in a rotenone model for Parkinson's disease.

Previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) engraftment could alleviate motor dysfunction in parkinsonian animal models, but with limited efficacy and few engrafted cells surviving. On the other side, basic fibroblast growth factor (bFGF) reportedly displays many effects including neuroprotection and promoting multipotent cells to expand and differentiate. In this study, we assessed whether a combination of bFGF and human BMSCs (HBMSCs) therapy could enhance the treatment effectiveness in Parkinson's disease (PD) rat models. Specifically, bFGF promoted HBMSCs to transdifferentiate toward neural-like lineages in vitro. In addition, HBMSCs transplantation alleviated the motor functional asymmetry, as well as prevented dopaminergic neuron loss in a PD model, while bFGF administration enhances its neurodifferentiation capacity and therapeutic effect. In conclusion, optimizing culture condition like supplementation of bFGF could significantly improve the output of HBMSCs in vitro, and HBMSCs transplantation with bFGF might represent an improved transplantation approach for PD.

Dl-3-n-butylphthalide, a natural antioxidant, protects dopamine neurons in rotenone models for Parkinson's disease.

In the absence of a cure for Parkinson's disease, development of preventive medications for this devastating disease is particularly encouraged. Dl-3-n-butylphthalide (NBP), an established natural antioxidant for clinical stroke treatment in China, can reportedly reduce beta-amyloid-induced neuronal toxicity in cultured neuronal cells, and attenuate neurodegenerative changes in aged rats. However, whether or not NBP confers neuroprotection in parkinsonian models is still unknown. In this study, we investigated the effects of NBP in rotenone models for Parkinson's diseases. In a cellular model, pretreatment with NBP enhanced cell viability by decreasing nuclear fragmentation, retaining mitochondrial membrane potential, and preventing reactive oxygen species (ROS) from generation. In a rodent model, 2-week treatment with NBP was able to ameliorate apomorphine-evoked rotations by 48% and rescue dopaminergic (DA) neurons by 30% and striatal DA terminal by 49%. Furthermore, NBP upregulated the vesicular monoamine transporter 2 gene expression in vitro and in vivo. Together, NBP protects DA neurons likely by reducing oxidative stress, offering an alternative neuroprotective medication for Parkinson's disease.