Effect of a dendritic cells derived extracellular vesicle as therapeutic vaccine platform to induce neuroprotective immunity for spinal cord injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE235618 | GEO | 2024/06/22
REPOSITORIES: GEO
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Project description:Effect of a dendritic cells derived extracellular vesicle as therapeutic vaccine platform to induce neuroprotective immunity for spinal cord injury
| PRJNA986559 | ENA
Project description:Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits. The currently available treatments involve surgical, medical, and rehabilitative strategies. However, none of these techniques can markedly reverse neurological deficits. Recently, extracellular vesicles from various cell sources have been applied to different models of spinal cord injury, thereby generating new cell-free therapies for the treatment of spinal cord injury. However, the use of extracellular vesicles alone is still associated with some notable shortcomings, such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons. Therefore, this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury, including the combination of extracellular vesicles with nanoparticles, exogenous drugs and/or biological scaffold materials, which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles. We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
| S-EPMC10503620 | biostudies-literature
Project description:Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into β3-tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI.
| S-EPMC9256979 | biostudies-literature
Project description: Not available
| S-EPMC6262995 | biostudies-literature
Project description:Spinal cord injury (SCI) has emerged as a prevalent condition with limited effective treatment options. The neuroprotective role of pramipexole (PPX) in inhibiting nerve cell apoptosis in central nervous system injuries is well established. Therefore, we investigated the effects of PPX in SCI. Adult Sprague-Dawley rats were divided into four groups (sham, SCI, PPX-0.25, and PPX-2.0 groups) according to the PPX therapy (n = 24). Then, SCI was induced using the modified Allen method, and PPX was intravenously administered into the tail at dosages of 0.25 or 2.0 mg/kg following the injury. Motor function was evaluated using the Rivlin-modified inclined plate apparatus and the Basso Beattie Bresnahan (BBB) workout scale. Western blotting assay was used to measure protein expression levels of DRD2, NeuN, Bax/Bcl-2, and caspase-3. Furthermore, immunohistochemistry assessed the effect of PPX on the quantity of NeuN-positive cells in the spinal cord tissue after SCI. Our findings revealed that the BBB and slanting board test scores of the PPX-treated model groups were considerably higher for the SCI group and significantly lower for the sham operation group (P < 0.001). Moreover, the PPX-2.0 group exhibited significantly higher NeuN expression levels than the SCI group (P < 0.01). Our findings indicate that PPX exerts a neuroprotective effect in secondary neuronal injury following SCI, facilitating the recovery of hind limb function by downregulating Bax/Bcl-2, caspase-3, and IL-1β.
| S-EPMC10501368 | biostudies-literature
Project description:Astrocytes differentiate into a spectrum of neurotoxic and neuroprotective reactive subpopulations after CNS injury and in disease. In astrocyte conditional ADCY10 (sAC) knockout mice, reactive astrocytes exhibit a shift towards neurotoxic phenotypes implicating sAC as a critical regulator of neuroprotective astrocyte differentiation.
2023-12-11 | GSE237675 | GEO
Project description:Excess glutamate release and associated neurotoxicity contributes to cell death after spinal cord injury (SCI). Indeed, delayed administration of glutamate receptor antagonists after SCI in rodents improves tissue sparing and functional recovery. Despite their therapeutic potential, most glutamate receptor antagonists have detrimental side effects and have largely failed clinical trials. Topiramate is an AMPA-specific, glutamate receptor antagonists that is FDA-approved to treat CNS disorders. In the current study we tested whether topiramate treatment is neuroprotective after cervical contusion injury in rats. We report that topiramate, delivered 15-minutes after SCI, increases tissue sparing and preserves oligodendrocytes and neurons when compared to vehicle treatment. In addition, topiramate is more effective than the AMPA-receptor antagonist, NBQX. To the best of our knowledge, this is the first report documenting a neuroprotective effect of topiramate treatment after spinal cord injury.
| S-EPMC3302770 | biostudies-literature
Project description:Spinal cord injury (SCI) is a devastating event resulting in permanent loss of neurological function. To date, effective therapies for SCI have not been established. With recent progress in neurobiology, however, there is hope that drug administration could improve outcomes after SCI. Riluzole is a benzothiazole anticonvulsant with neuroprotective effects. It has been approved by the U.S. Food and Drug Administration as a safe and well-tolerated treatment for patients with amyotrophic lateral sclerosis. The mechanism of action of riluzole involves the inhibition of pathologic glutamatergic transmission in synapses of neurons via sodium channel blockade. There is convincing evidence that riluzole diminishes neurological tissue destruction and promotes functional recovery in animal SCI models. Based on these results, a phase I/IIa clinical trial with riluzole was conducted for patients with SCI between 2010 and 2011. This trial demonstrated significant improvement in neurological outcomes and showed it to be a safe drug with no serious adverse effects. Currently, an international, multi-center clinical trial (Riluzole in Acute Spinal Cord Injury Study: RISCIS) in phase II/III is in progress with riluzole for patients with SCI (clinicaltrials.gov, registration number NCT01597518). This article reviews the pharmacology and neuroprotective mechanisms of riluzole, and focuses on existing preclinical evidence, and emerging clinical data in the treatment of SCI.
| S-EPMC6272473 | biostudies-literature
Project description:BackgroundTetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used in many ischemia disorders treatments. However, the exact mechanism by which TMP protects the spinal cord ischemia/reperfusion (I/R) injury is still unknown. For this purpose, rabbits were randomly divided into sham group, control group and TMP group. After the evaluation of neurologic function, the spinal cords were immediately removed for biochemical and histopathological analysis. Apoptosis was measured quantitatively by the terminal transferase UTP nick end-labeling (TUNEL) method and confirmed by electron microscopic examination, the expression of Bax and Bcl-2 was immunohistochemically evaluated and quantified by Western blot analysis.ResultsNeurologic outcomes in the TMP-group were significantly better than those in the control group (P < 0.05). TMP decreased spinal cord malondialdehyde (MDA) levels and ameliorated the down regulation of spinal cord superoxide dismutase (SOD) activity. TMP significantly reduced the loss of motoneurons and TUNEL-positive rate. Greater Bcl-2 and attenuated Bax expression was found in the TMP treating rabbits.ConclusionThese findings suggest that TMP has protective effects against spinal cord I/R injury by reducing apoptosis through regulating Bcl-2 and Bax expression.
| S-EPMC1534051 | biostudies-literature
Project description:Spinal cord injury (SCI) induces a sequence of endogenous autodestructive changes known as secondary injury, as well as reactive biochemical changes that are neuroprotective and/or promote recovery. All these responses to SCI are, in part reflected in changes in gene expression. In order to assess changes in gene expression involved in the regeneration process,microarrays were performed as a function of time after SCI for the various treatments.
2012-01-01 | GSE29488 | GEO