Targeting Non-Coding RNA for CNS Injuries: Regulation of Blood-Brain Barrier Functions.

Central nervous system (CNS) injuries are the most common cause of death and disability around the world. The blood-brain barrier (BBB) is located at the interface between the CNS and the surrounding environment, which protects the CNS from exogenous molecules, harmful agents or microorganisms in the blood. The disruption of BBB is a common feature of CNS injuries and participates in the pathological processes of secondary brain damage. Recently, a growing number of studies have indicated that non-coding RNAs (ncRNAs) play an important role in brain development and are involved in CNS injuries. In this review, we summarize the mechanisms of BBB breakdown after CNS injuries. We also discuss the effects of ncRNAs including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) on BBB damage in CNS injuries such as ischemic stroke, traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). In addition, we clarify the pharmacotherapies that could regulate BBB function via ncRNAs in CNS injuries, as well as the challenges and perspectives of ncRNAs on modulation of BBB function. Hence, on the basis of these effects, ncRNAs may be developed as therapeutic agents to protect the BBB for CNS injury patients.

Human umbilical cord mesenchymal stem cell-derived exosomes provide neuroprotection in traumatic brain injury through the lncRNA TUBB6/Nrf2 pathway.

Recently, human umbilical cord mesenchymal stem cell (HucMSC) is a new focus of research in neurological diseases, and the beneficial effect of HucMSC is mediated by paracrine factors which are transported by exosome. Our previous study has shown that HucMSC-derived exosome could provide neuroprotection after traumatic brain injury (TBI). However, the underlying mechanisms were not fully understood. In the present study, we found that administration of exosome suppressed TBI-induced inflammation and ferroptosis. In addition, exosome activated the long non-coding ribonucleic acid (lncRNA) TUBB6/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway after TBI. However, exosome partly failed to provide neuroprotection following TBI when TUBB6 was knockdown. Importantly, exosome treatment also decreased neuron cell death, suppressed inflammation, inhibited ferroptosis and activated the lncRNA TUBB6/Nrf2 pathway after TBI in vitro. Taken together, our results provided the first evidence that HucMSC-derived exosome played a key role in neuroprotection after TBI through the lncRNA TUBB6/Nrf2 pathway.

Role of O-GlcNAcylation in Central Nervous System Development and Injuries: A Systematic Review.

The development of central nervous system (CNS) can form perceptual, memory, and cognitive functions, while injuries to CNS often lead to severe neurological dysfunction and even death. As one of the prevalent post-translational modifications (PTMs), O-GlcNAcylation has recently attracted great attentions due to its functions in regulating the activity, subcellular localization, and stability of target proteins. It has been indicated that O-GlcNAcylation could interact with phosphorylation, ubiquitination, and methylation to jointly regulate the function and activity of proteins. Furthermore, a growing number of studies have suggested that O-GlcNAcylation played an important role in the CNS. During development, O-GlcNAcylation participated in the neurogenesis, neuronal development, and neuronal function. In addition, O-GlcNAcylation was involved in the progress of CNS injuries including ischemic stroke, subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) and played a crucial role in the improvement of brain damage such as attenuating cognitive impairment, inhibiting neuroinflammation, suppressing endoplasmic reticulum (ER) stress, and maintaining blood-brain barrier (BBB) integrity. Therefore, O-GlcNAcylation showed great promise as a potential target in CNS development and injuries. In this article, we presented a review highlighting the role of O-GlcNAcylation in CNS development and injuries. Hence, on the basis of these properties and effects, intervention with O-GlcNAcylation may be developed as therapeutic agents for CNS diseases.

Application of PLGA/type I collagen/chitosan artificial composite dura mater in the treatment of dural injury.

To improve the safety of dura repair in neurological surgeries, a new poly (glycolide-co-lactide)/type I collagen/chitosan artificial composite dura mater was evaluated in a rabbit model with dura mater injury. Eighteen rabbits were randomized to 3 groups: rabbits with unclosed dura mater; rabbits with dura mater repaired by fascia and rabbits with dura mater repaired by the composite membrane. Modified combine behavior score were given at a series of time points and several cytokines were also determined to reflect the inflammatory conditions. Rabbits whose dura mater was repaired by composite membrane showed a similar recovery rate of neurological function and inflammatory condition compared with the rabbits whose dura mater was repaired by fascia. In addition, the rabbits with closed dura mater were better than ones with unclosed dura mater in the restore rate of neurological function as well as inflammatory reactions according to the statistical analysis. The new artificial membrane appears to be safe and efficient in the treatment of dura mater defect.

Human umbilical cord mesenchymal stem cell-derived exosome suppresses programmed cell death in traumatic brain injury via PINK1/Parkin-mediated mitophagy.

AIMS: Recently, human umbilical cord mesenchymal stem cell (HucMSC)-derived exosome is a new focus of research in neurological diseases. The present study was aimed to investigate the protective effects of HucMSC-derived exosome in both in vivo and in vitro TBI models. METHODS: We established both mouse and neuron TBI models in our study. After treatment with HucMSC-derived exosome, the neuroprotection of exosome was investigated by the neurologic severity score (NSS), grip test score, neurological score, brain water content, and cortical lesion volume. Moreover, we determined the biochemical and morphological changes associated with apoptosis, pyroptosis, and ferroptosis after TBI. RESULTS: We revealed that treatment of exosome could improve neurological function, decrease cerebral edema, and attenuate brain lesion after TBI. Furthermore, administration of exosome suppressed TBI-induced cell death, apoptosis, pyroptosis, and ferroptosis. In addition, exosome-activated phosphatase and tensin homolog-induced putative kinase protein 1/Parkinson protein 2 E3 ubiquitin-protein ligase (PINK1/Parkin) pathway-mediated mitophagy after TBI. However, the neuroprotection of exosome was attenuated when mitophagy was inhibited, and PINK1 was knockdown. Importantly, exosome treatment also decreased neuron cell death, suppressed apoptosis, pyroptosis, and ferroptosis and activated the PINK1/Parkin pathway-mediated mitophagy after TBI in vitro. CONCLUSION: Our results provided the first evidence that exosome treatment played a key role in neuroprotection after TBI through the PINK1/Parkin pathway-mediated mitophagy.

Fucoxanthin ameliorates traumatic brain injury by suppressing the blood-brain barrier disruption.

Fucoxanthin is the most abundant marine carotenoid extracted from seaweed. Our previous study has shown that fucoxanthin inhibited oxidative stress after traumatic brain injury (TBI). However, the effects of fucoxanthin on TBI-induced blood-brain barrier (BBB) destruction have not been well understood. In the present study, we found that fucoxanthin improved neurological dysfunction, reduced brain edema, attenuated cortical lesion volume, and decreased dendrites loss after TBI in vivo. Moreover, fucoxanthin suppressed BBB leakage, preserved tight junction (TJ) and adherens junction (AJ) proteins, and inhibited MMP-9 expression. Furthermore, fucoxanthin alleviated apoptosis and ferroptosis, and activated mitophagy in endothelial cells (ECs) after TBI. However, the protection of fucoxanthin on BBB was attenuated when mitophagy was inhibited. Importantly, fucoxanthin also provided protective effects in bEnd.3 cells after TBI. Taken together, our results suggested that fucoxanthin played a key role in the protection of BBB after TBI through mitophagy.

Prevalence of heterotopic ossification after cervical total disc arthroplasty: a meta-analysis.

BACKGROUND: Heterotopic ossification (HO) is a well-known complication after total hip and knee arthroplasty. But limited studies have focused on prevalence of HO following cervical total disc arthroplasty (CTDA) and the published data show controversial results. OBJECTIVE: The purpose of this review is to investigate the prevalence of HO following CTDA by meta-analysis. METHODS: The literatures were collected from PubMed, Embase and Cochrane library by using keywords as ([disc or disk] and [arthroplasty or replacement]) and (HO or delayed fusion or spontaneous fusion). The original studies were eligible only if the prevalence of HO and of advanced HO (Grade 3-4 according to McAfee) were investigated. A meta-analysis was then performed on collected data. Statistical heterogeneity across the various trials was tested using Cochran's Q, statistic and in the case of heterogeneity a random effect model was used. Tests of publication bias and sensitivity analysis were also performed. RESULTS: Our data showed that the pooled prevalence of HO was 44.6% (95% confidence interval (CI), 37.2-45.6%) 12 months after CTDA and 58.2% (95% CI, 29.7-86.8%) 24 months after CTDA, while the advanced HO was 11.1% (95% CI, 5.5-16.7%) and 16.7% (95% CI, 4.6-28.9%), respectively. A significant heterogeneity was obtained. There was no publication bias and individual study had no significant effect on the pooled prevalence estimate. CONCLUSION: Higher prevalence of HO was observed following CTDA, although HO was reported to be unrelated to the clinical improvement. It suggests that cervical disc replacement should be performed cautiously before obtaining long-term supporting evidence. LEVEL OF EVIDENCE: Prognostic level III.

Soleus muscle H-reflex monitoring in endoscopic surgery under general anesthesia percutaneous interlaminar approach.

The clinical value of soleus muscle H-reflex monitoring in general anesthesia percutaneous interlaminar approach was investigated. A total of 80 cases with unilateral L5-S1 disc herniation between January 2015 and October 2016 were randomly divided into control group (without soleus muscle H-reflex monitoring, n=40) and observation group (with soleus muscle H-reflex monitoring, n=40). Results showed that the operation time of the observation group was shorter than that of the control group (P<0.05), and the blood loss during the operation was less than that of the control group (P<0.05). The length of postoperative hospital stay was shorter than that of the control group (P<0.05). At 24 h after operation, the amplitude of H-reflex in diseased side soleus muscle was significantly lower than that in healthy side (P<0.05). The preoperative, postoperative and 24 h postoperatively, the latency of H-reflex in diseased side soleus muscle was shorter than that of healthy side (P<0.05). The latency and amplitude of H-reflex latency in soleus muscle were significantly lower (P<0.05), and the height of intervertebral space in observation group was significantly higher than that in control group (P<0.05). The total percentage of postsurgical sensory dysfunction, dyskinesia, post-root canal stenosis, disc herniation and cerebrospinal fluid leakage was lower than that of the control group (P<0.05). Japanese Orthopaedic Association score of the observation group was significantly higher at 1 month, and 1 year after operation lower than the control group (P<0.05). Taken together, soleus muscle H-reflex monitoring can effectively reduce the damage to the nerve roots under percutaneous endoscopic intervertebral endoscopic surgery under general anesthesia, improve the accuracy of surgery, reduce the complications, shorten the operation time and reduce the surgical bleeding, which is more beneficial to patients smooth recovery.