Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.
Epilepsy is a group of enduring neurological disorder characterized by spontaneous and recurrent seizures with heterogeneous etiology, clinical expression, severity, and prognosis. Growing body of research investigates that epileptic seizures are originated from neuronal synchronized and excessive electrical activity. However, the underlying molecular mechanisms of epileptogenesis have not yet been fully elucidated and 30% of epileptic patients still are resistant to the currently available pharmacological treatments with recurrent seizures throughout life. Over the past two decades years accumulated evidences provide strong support to the hypothesis that neuroinflammation, including microglia and astrocytes activation, a cascade of inflammatory mediator releasing, and peripheral immune cells infiltration from blood into brain, is associated with epileptogenesis. Meanwhile, an increasing body of preclinical researches reveal that the anti-inflammatory therapeutics targeting crucial inflammatory components are effective and promising in the treatment of epilepsy. The aim of the present study is to highlight the current understanding of the potential neuroinflammatory mechanisms in epileptogenesis and the potential therapeutic targets against epileptic seizures.
As a new network technology, mobile-edge computing (MEC) combined with the Internet of Vehicles (IoV) can effectively improve the efficiency of task computing and offloading. However, the power of edge computing will be severely limited to the areas with poor MEC server coverage. Furthermore, there are a number of peripheral vehicles with temporarily idle computing resources on the road, so how to put the resources of these vehicles into use becomes the primary issue to be considered. In this article, a distributed multihop task offloading decision model for task execution efficiency is developed, which mainly consists of two parts: 1) a candidate vehicle selection mechanism for screening the neighboring vehicles that can participate in offloading and 2) a task offloading decision algorithm for obtaining the task offloading solution. Considering the impact of different hop and wireless communication ranges on communication ranges on task completion in a generic scenario, we introduce the hop count $k$ and select the neighboring vehicles in the $k$ -hop wireless communication range as the candidate vehicles. Then, the problem of offloading is modeled as a generalized allocation model with constraints which is solved by the greedy algorithm and discrete bat algorithm, respectively. The results show that compared with the scheme in which the task vehicle randomly selects the neighboring vehicles to offload and the scheme that all tasks are completed locally, the offloading scheme in which all tasks are completed under the greedy algorithm or bat-based algorithm has advantages in time delay performance in terms of different task number, task required computation power, and task size environment. Besides, this article also explores the influence of hop count $k$ on the results when selecting candidate vehicles from the neighboring vehicles within the range of $k$ hop. The results show that the increase of $k$ will also increase the number of candidate vehicles, which makes the time delay lower. Under the parameters set in this article, the time delay required for the greedy algorithm offloading scheme to complete all tasks is a lower bound on the time delay of the bat algorithm scheme. The greedy algorithm scheme reduces latency by 0.2–2.4 s compared to the scheme where tasks are all completed locally, and it reduces latency by 0.16–2.3 s compared to the random offloading scheme.
Objective:Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke.Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury.However,plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke.This study aims to explore the role of delayed recanalization on blood-brain barrier(BBB)in the penumbra(surrounding ischemic core)and neurological outcomes after middle cerebral artery occlusion(MCAO).Methods:Recanalization was performed on the 3rd day after MCAO.BBB disruption was tested by Western blotting,Evans blue dye,and immunofluorescence staining.Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO.The expression of fibroblast growth factor 21(FGF21),fibroblast growth factor receptor 1(FGFR1),phosphatidylinositol-3-kinase(PI3K),and serine/threonine kinase(Akt)in the penumbra were observed by immunofluorescence staining and/or Western blotting.Results:The extraversion of Evans blue,IgG,and albumin increased surrounding ischemic core after MCAO,but significantly decreased after recanalization.The expression of Claudin-5,Occludin,and zona occludens 1(ZO-1)decreased surrounding ischemic core after MCAO,but significantly increased after recanalization.Infarct volume reduced and neurological outcomes improved following recanalization(on the 7th day after MCAO).The expressions of Claudin-5,Occludin,and ZO-1 decreased surrounding ischemic core following MCAO,which were up-regulated corresponding to the increases of FGF21,p-FGFR1,PI3K,and p-Akt after recanalization.Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K,p-Akt,Occludin,Claudin-5,and ZO-1 in the penumbra,which weakened the beneficial effects of recanalization on neurological outcomes after MCAO.Conclusion:Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway,which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
The Internet of Vehicles (IoV) has attracted increasing attentions for its potential of enhancing driving safety and traffic efficiency. The Multi-hop broadcast is one of the important techniques for time-sensitive data dissemination especially in emergent cases. As a result, how to wisely select the next-hop during Multi-hop routing plays an important role for performance improvement in IoV as well as dependent applications. Nevertheless, in view of the high mobility, frequent changing topology and complicated channel environment, a hazardous and thoughtless selection of the next-hop is easy to make, thus leading undesirable results. To deal with this issue, in this paper, a probabilistic broadcasting protocol for emergent message dissemination (BP-EMD) in Urban IoV is proposed. As the selection guidance for relaying node, the weighted probability is envisioned for each potential relay candidate, which is the combination of distance, link availability and packet reception ratio. After that, the node with the greatest weighted probability has been given the highest priority to relay the packet. In case that the selected relay node fails the forwarding, the other nodes available for relay will assist to disseminate the packet. In this way, the transmission reliability of the emergent messages is significantly guaranteed. Numerical results indicate that our BP-EMD can achieve higher broadcasting efficiency and less redundancy with less delivery latency, average transmission numbers and average End-to-End delay, as well as high packets delivery ratio and dissemination efficiency, compared with some classical multi-hop broadcasting protocols.