Restoration Of Nerve Function Research Articles

Activation of P2X7R Inhibits Proliferation and Promotes the Migration and Differentiation of Schwann Cells.

In the vertebrate nervous system, myelination of nerve fibers is crucial for the rapid propagation of action potentials through saltatory conduction. Schwann cells-the main glial cells and myelinating cells of the peripheral nervous system-play a crucial role in myelination. Following injury during the repair of peripheral nerve injuries, a significant amount of ATP is secreted. This ATP release acts to trigger the dedifferentiation of myelinating Schwann cells into repair cells, an essential step for axon regeneration. Subsequently, to restore nerve function, these repair cells undergo redifferentiate into myelinating Schwann cells. Except for P2X4R, purine receptors such as P2X7R also play a significant role in this process. In the current study, decreased expression of P2X7R was observed after sciatic nerve injury, followed by a gradual increase to the normal level of P2X7R expression. In vivo experiments showed that the activation of P2X7R using an agonist injection promoted remyelination, while the antagonists hindered remyelination. Further, in vitro experiments supported these findings and demonstrated that P2X7R activation inhibited the proliferation of Schwann cells, but it promoted the migration and differentiation of the Schwann cells. Remyelination is a prominent feature of the nerve regeneration. In the current study, it was proposed that the manipulation of P2X7R expression in Schwann cells after nerve injury could be effective in facilitating nerve remyelination.

Radiofrequency ablation for the cervical spine.

Radiofrequency ablation (RFA), a minimally invasive procedure for pain reduction, is increasingly used for managing chronic neck pain and headaches. This article offers a concise overview of cervical spine RFA. In the context of RFA, heat is applied to specific nerve tissues to interrupt pain signals. Wallarian degeneration occurs as a result of the thermal injury to the nerve. The heat generated by the RFA procedure can damage the nerve fibers, initiating the degenerative process. Wallarian degeneration is a process that occurs in a nerve axon due to the thermal injury, leading to the breakdown and eventual degradation of the axon and its myelin sheath. However, nerves have regeneration capacity, especially the peripheral nerves, which are often the target of RFA for pain management. After Wallarian degeneration takes place, the nerve sheath, or the connective tissue surrounding the nerve, can serve as a scaffold for the growth of new nerve fibers. Over time, these new fibers can regenerate and re-establish connections, potentially restoring nerve function. Three common types are traditional thermal, water-cooled, and pulsed radio frequency ablation. Given the regenerative potential of nerves, these procedures are typically effective for 1 to 2 years, with some variability. Despite a 112% increase in Medicare claims for RFA from 2009 to 2018, it's recommended for patients who respond positively to diagnostic medial branch blocks, with recent guidelines suggesting a single block may be sufficient. Although generally effective, the procedure carries risks, including nerve and tissue injury. Notably, the procedure's increased utilization notably surpasses the most commonly reported prevalence rates of conditions it aims to treat. Moreover, diagnostic blocks performed before cervical RFA also have their risks, such as inadvertent vascular injections leading to seizures or paralysis. In summary, the risks and benefits of cervical RFA must be considered with regards to the patient's comorbidities and specific pain issues. The skill and experience of the practitioner plays a significant role in minimizing these risks. Detailed discussions with healthcare providers about the risks, benefits, and alternatives can help in making an informed decision about the procedure.

PEDOT-Integrated Fish Swim Bladders as Conductive Nerve Conduits.

Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4-ethylenedioxythiophene) (PEDOT)-integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre-coating with polydopamine. The obtained PEDOT/IKVAV-integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV-integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV-integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB-derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long-segment neural defects.

Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives.

Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.

Sea Cucumber-Inspired Microneedle Nerve Guidance Conduit for Synergistically Inhibiting Muscle Atrophy and Promoting Nerve Regeneration.

Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient's mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs' migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.

Salidroside promotes angiogenesis after cerebral ischemia in mice through Shh signaling pathway

AimsThe purpose of this study was to explore the impacts of salidroside on vascular regeneration, vascular structural changes and long-term neurological recuperation following cerebral ischemia and its possible mechanism. Main methodsFrom Day 1 to Day 28, young male mice with middle cerebral artery blockage received daily doses of salidroside and measured neurological deficits. On the 7th day after stroke, the volume of cerebral infarction was determined using TTC and HE staining. Microvascular density, astrocyte coverage, angiogenesis and the expression of the Shh signaling pathway were detected by IF, qRTPCR and WB at 7, 14 and 28 days after stroke. Changes in blood flow, blood vessel density and diameter from stroke to 28 days were measured by the LSCI and TPMI. Key findingsCompared with the dMACO group, the salidroside treatment group significantly promoted the recovery of neurological function. Salidroside was found to enhance cerebral blood flow perfusion and reduce the infarct on the 7th day after stroke. From the 7th to the 28th day after stroke, salidroside treatment boosted the expression of CD31, CD31+/BrdU+, and GFAP in the cortex around the infarction site. On the 14th day after stroke, salidroside significantly enhanced the width and density of blood vessels. Salidroside increased the expression of histones and genes in the Shh signaling pathway during treatment, and this effect was weakened by the Shh inhibitor Cyclopamine. SignificanceSalidroside can restore nerve function, improve cerebral blood flow, reduce cerebral infarction volume, increase microvessel density and promote angiogenesis via the Shh signaling pathway.

Exosomes derived from human umbilical cord mesenchymal stem cells decrease neuroinflammation and facilitate the restoration of nerve function in rats suffering from intracerebral hemorrhage.

Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-ex) have become a hopeful substitute for whole-cell therapy due to their minimal immunogenicity and tumorigenicity. The present study aimed to investigate the hypothesis that hUCMSC-ex can alleviate excessive inflammation resulting from intracerebral hemorrhage (ICH) and facilitate the rehabilitation of the nervous system in rats. In vivo, hemorrhagic stroke was induced by injecting collagenase IV into the striatum of rats using stereotactic techniques. hUCMSC-ex were injected via the tail vein at 6h after ICH model establishment at a dosage of 200µg. In vitro, astrocytes were pretreated with hUCMSC-ex and then stimulated with hemin (20μmol/mL) to establish an ICH cell model. The expression of TLR4/NF-κB signaling pathway proteins and inflammatory factors, including TNF-α, IL-1β, and IL-10, was assessed both in vivo and in vitro to investigate the impact of hUCMSC-ex on inflammation. The neurological function of the ICH rats was evaluated using the corner turn test, forelimb placement test, Longa score, and Bederson score on the 1st, 3rd, and 5th day. Additionally, RT-PCR was employed to examine the mRNA expression of TLR4 following hUCMSC-ex treatment. The findings demonstrated that hUCMSC-ex downregulated the protein expression of TLR4, NF-κB/P65, and p-P65, reduced the levels of pro-inflammatory cytokines TNF-α and IL-1β, and increased the expression of the anti-inflammatory cytokine IL-10. Ultimately, the administration of hUCMSC-ex improved the behavioral performance of the ICH rats. However, the results of PT-PCR indicated that hUCMSC-ex did not affect the expression of TLR4 mRNA induced by ICH, suggesting that hUCMSCs-ex may inhibit TLR4 translation rather than transcription, thereby suppressing the TLR4/NF-κB signaling pathway. We can conclude that hUCMSC-ex mitigates hyperinflammation following ICH by inhibiting the TLR4/NF-κB signaling pathway. This study provides preclinical evidence for the potential future application of hUCMSC-ex in the treatment of cerebral injury.

Engineering Innervated Musculoskeletal Tissues for Regenerative Orthopedics and Disease Modeling.

Musculoskeletal (MSK) disorders significantly burden patients and society, resulting in high healthcare costs and productivity loss. These disorders are the leading cause of physical disability, and their prevalence is expected to increase as sedentary lifestyles become common and the global population of the elderly increases. Proper innervation is critical to maintaining MSK function, and nerve damage or dysfunction underlies various MSK disorders, underscoring the potential of restoring nerve function in MSK disorder treatment. However, most MSK tissue engineering strategies have overlooked the significance of innervation. This review first expounds upon innervation in the MSK system and its importance in maintaining MSK homeostasis and functions. This will be followed by strategies for engineering MSK tissues that induce post-implantation in situ innervation or are pre-innervated. Subsequently, research progress in modeling MSK disorders using innervated MSK organoids and organs-on-chips (OoCs) is analyzed. Finally, the future development of engineering innervated MSK tissues to treat MSK disorders and recapitulate disease mechanisms is discussed. This review provides valuable insights into the underlying principles, engineering methods, and applications of innervated MSK tissues, paving the way for the development of targeted, efficacious therapies for various MSK conditions.

Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP–SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM). To overcome the limitation of traditional tissue-engineered nerve grafts, jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration. To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration, we performed a cDNA microarray analysis of gene expression profiling, a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues. A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration. Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.

Doping-induced assembly interface for noninvasive in vivo local and systemic immunomodulation.

Peripheral neural interfaces, potent in modulating local and systemic immune responses for disease treatment, face significant challenges due to the peripheral nerves' broad distribution in tissues like the fascia, periosteum, and skin. The incongruity between static electronic components and the dynamic, complex organization of the peripheral nervous system often leads to interface failure, stalling circuit research and clinical applications. To overcome these, we developed a self-assembling, tissue-adaptive electrode composed of a single-component cocktail nanosheet colloid, including dopants, conducting polymers, stabilizers, and an MXene catalyst. Delivered via a jet injector to designated nerve terminals, this assembly utilizes reactive oxygen species to catalytically dope poly (3,4-ethylenedioxythiophene), enhancing π-π interactions between nanosheets, and yielding a conductive, biodegradable interface. This interface effectively regulates local immune activity and promotes sensory and motor nerve functional restoration in nerve-injured mice, while engaging the vagal-adrenal axis in freely moving mice, eliciting catecholamine neurotransmitter release, and suppressing systemic cytokine storms. This innovative strategy specifically targets nerve substructures, bolstering local and systemic immune modulation, and paving the way for the development of self-adaptive dynamic neural interfaces.

Fibular canal syndrome: modern principles of diagnosis and treatment

Fibular tunnel syndrome is the most common tunnel syndrome of the lower extremity. Compression of the fibular nerve most often occurs at the level of the fibular head. The article describes in detail the etiology and pathogenesis of this tunnel neuropathy. Clinical manifestations of fibular tunnel syndrome are considered, methods of diagnosis and treatment are described. The prognosis of peroneal nerve neuropathy is favorable, and in most patients there is a complete or almost complete restoration of nerve function. If conservative treatment is ineffective, surgical techniques are recommended.

Comparison between the Effects of Ultrasound Guided Local Insulin Injections versus Hydrodissection of Normal Saline in Carpal Tunnel Syndrome Patients with Diabetes Mellitus

Background Hydrodissection is a minimally invasive procedure of injecting fluid into anatomic spaces to facilitate dissection and adhesiolysis in peripheral nerve entrapments. The near-nerve local insulin injection is thought to promote neuronal growth and regeneration, and could be important in restoring nerve function following metabolic or vascular damage. Aim of the Work to compare the short-term effects of insulin and normal saline local injections in the treatment of patients with diabetes mellitus who have mild-to-moderate carpal tunnel syndrome. Patients and Methods A comparative study was conducted on 30 carpal tunnel syndrome patients with diabetes mellitus during recruited from Ain Shams University Hospital, Neurosonology, neurology department during the period January 2020 to March 2021 according to the regulation of Ain Shams University ethical and scientific committee. The privacy of participants and confidentiality of the data were guaranteed during various phases of the study. Results the Hydrodissection (10 ml of normal saline) of the median nerve is significantly effective in the treatment of mild to moderate carpal tunnel syndrome in patients with diabetes mellitus and alleviates the symptoms of CTS. Also the study showed that the local insulin injection (10 IU of NPH) alone is significantly effective in the management of mild to moderate carpal tunnel syndrome of diabetic patients, which shows significant response within two weeks of follow up. The study shows that Hydrodissection is slightly superior to insulin for treatment of CTS. Furthermore our current study compares the failure rate of both treatment modalities which implies that Hydrodissection group are less failure rate than insulin group, but this difference is insignificant due small sample size of both groups. Conclusion Hydrodissection and local insulin injection are effective methods in the management of mild to moderate Carpal Tunnel Syndrome of diabetic patients with superiority of ultrasound guided hydrodissection to Insulin. It is noteworthy this study is considered a pioneer in comparing HD and Insulin in managing CTS.

Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury.

Over the years, electroconductive hydrogels (ECHs) have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury (PNI) with diabetes, given their favorable mechanical and electrical properties identical to endogenous nerve tissue. Nevertheless, PNI causes the loss of locomotor function and inflammatory pain, especially in diabetic patients. It has been established that bone marrow stem cells-derived exosomes (BMSCs-Exos) have analgesic, anti-inflammatory and tissue regeneration properties. Herein, we designed an ECH loaded with BMSCs-Exos (ECH-Exos) electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief. Given its potent adhesive and self-healing properties, this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure, avoiding the cumbersome implantation process. Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells. Meanwhile, Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway, thereby attenuating inflammatory pain in diabetic PNI. Additionally, ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo, consequently ameliorating muscle denervation atrophy and further promoting functional restoration. Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration, functional restoration and pain relief in patients with diabetic PNI.

Muscle-derived stem cell exosomes with overexpressed miR-214 promote the regeneration and repair of rat sciatic nerve after crush injury to activate the JAK2/STAT3 pathway by targeting PTEN.

This study aimed to investigate the effect of muscle-derived stem cell (MDSC) exosomes with overexpressed miR-214 on the regeneration and repair of rat sciatic nerve after crush injury and its molecular mechanism. First, primary MDSCs, Schwann cells (SCs) and dorsal root ganglion (DRG) neurons were isolated and cultured, and the characteristics of MDSCs-derived exosomes were identified by molecular biology and immunohistochemistry. NC mimics and miR-214 mimics were transfected to obtain exo-NC and exo-miR-214. An in vitro co-culture system was established to determine the effect of exo-miR-214 on nerve regeneration. The restoration of sciatic nerve function of rats by exo-miR-214 was evaluated by walking track analysis. Immunofluorescence for NF and S100 was used to detect the regeneration of axon and myelin sheath in injured nerve. The Starbase database was used to analyze the downstream target genes of miR-214. QRT-PCR and dual luciferase reporter assays were used to validate the miR-214 and PTEN interaction relationship. And the expression of the JAK2/STAT3 pathway-related proteins in sciatic nerve tissues were detected by western blot. The above experiments showed that MDSCs-derived exosomes with overexpressed miR-214 was found to promote the proliferation and migration of SCs, increase the expression of neurotrophic factors, promote axon extension of DRG neurons and positively affect the recovery of nerve structure and function. In addition, PTEN was a target gene of miR-214. Exo-miR-214 can significantly inhibit the expression level of PTEN, increase the protein expression levels of p-JAK2 and p-STAT3 and the ratio of p-JAK2/JAK2 and p-STAT3/STAT3, also MDSCs-derived exosomes with overexpressed miR-214 can reduce the occurrence of denervated muscle atrophy. In summary, the MDSCs-derived exosomes with overexpressed miR-214 is involved in peripheral nerve regeneration and repair in rats after sciatic nerve crush injury to activate the JAK2/ STAT3 pathway by targeting PTEN.

Biohybrid neural implant

An article in Science Advances reports a biohybrid neural interface device that integrates a cell layer on a microelectrode array, achieving high-resolution mapping of neuronal inputs and restoration of nerve function.

Nerve function restoration following targeted muscle reinnervation after varying delayed periods.

Targeted muscle reinnervation has been proposed for reconstruction of neuromuscular function in amputees. However, it is unknown whether performing delayed targeted muscle reinnervation after nerve injury will affect restoration of function. In this rat nerve injury study, the median and musculocutaneous nerves of the forelimb were transected. The proximal median nerve stump was sutured to the distal musculocutaneous nerve stump immediately and 2 and 4 weeks after surgery to reinnervate the biceps brachii. After targeted muscle reinnervation, intramuscular myoelectric signals from the biceps brachii were recorded. Signal amplitude gradually increased with time. Biceps brachii myoelectric signals and muscle fiber morphology and grooming behavior did not significantly differ among rats subjected to delayed target muscle innervation for different periods. Targeted muscle reinnervation delayed for 4 weeks can acquire the same nerve function restoration effect as that of immediate reinnervation.

Gut microbiota in a mouse model of obesity and peripheral neuropathy associated with plasma and nerve lipidomics and nerve transcriptomics

BackgroundPeripheral neuropathy (PN) is a common complication in obesity, prediabetes, and type 2 diabetes, though its pathogenesis remains incompletely understood. In a murine high-fat diet (HFD) obesity model of PN, dietary reversal (HFD-R) to a low-fat standard diet (SD) restores nerve function and the nerve lipidome to normal. As the gut microbiome represents a potential link between dietary fat intake and nerve health, the current study assessed shifts in microbiome community structure by 16S rRNA profiling during the paradigm of dietary reversal (HFD-R) in various gut niches. Dietary fat content (HFD versus SD) was also correlated to gut flora and metabolic and PN phenotypes. Finally, PN-associated microbial taxa that correlated with the plasma and sciatic nerve lipidome and nerve transcriptome were used to identify lipid species and genes intimately related to PN phenotypes.ResultsMicrobiome structure was altered in HFD relative to SD but rapidly reversed with HFD-R. Specific taxa variants correlating positively with metabolic health associated inversely with PN, while specific taxa negatively linked to metabolic health positively associated with PN. In HFD, PN-associated taxa variants, including Lactobacillus, Lachnoclostridium, and Anaerotruncus, also positively correlated with several lipid species, especially elevated plasma sphingomyelins and sciatic nerve triglycerides. Negative correlations were additionally present with other taxa variants. Moreover, relationships that emerged between specific PN-associated taxa variants and the sciatic nerve transcriptome were related to inflammation, lipid metabolism, and antioxidant defense pathways, which are all established in PN pathogenesis.ConclusionsThe current results indicate that microbiome structure is altered with HFD, and that certain taxa variants correlate with metabolic health and PN. Apparent links between PN-associated taxa and certain lipid species and nerve transcriptome-related pathways additionally provide insight into new targets for microbiota and the associated underlying mechanisms of action in PN. Thus, these findings strengthen the possibility of a gut-microbiome-peripheral nervous system signature in PN and support continuing studies focused on defining the connection between the gut microbiome and nerve health to inform mechanistic insight and therapeutic opportunities.5A96nAvwbUx__NCbnk38-bVideo

A tannic acid doped hydrogel with small extracellular vesicles derived from mesenchymal stem cells promotes spinal cord repair by regulating reactive oxygen species microenvironment

Spinal cord injury (SCI) is a serious disease of the central nervous system that is associated with a poor prognosis; furthermore, existing clinical treatments cannot restore nerve function in an effective manner. Inflammatory responses and the increased production of reactive oxygen species (ROS) in the microenvironment of the lesion are major obstacles that inhibit the recovery of SCI. Small extracellular vesicles (sEVs), derived from mesenchymal stem cells, are suitable options for cell-free therapy and have been shown to exert therapeutic effects in SCI, thus providing a potential strategy for microenvironment regulation. However, the effective retention, controlled release, and integration of small extracellular vesicles into injured spinal cord tissue are still a major challenge. Herein, we fabricated an N-acryloyl glycinamide/gelatin methacrylate/Laponite/Tannic acid (NAGA/GelMA/LPN/TA, NGL/T) hydrogel with sustainable sEV release (sEVs-NGL/T) to promote the recovery of motor function after SCI. The newly developed functional sEVs-NGL/T hydrogel exhibited excellent antioxidant properties in an H2O2-simulated peroxidative microenvironment in vitro. Implantation of the functional sEVs-NGL/T hydrogel in vivo could encapsulate sEVs, exhibiting efficient retention and the sustained release of sEVs, thereby synergistically inducing significant restoration of motor function and urinary tissue preservation. These positive effects can be attributed to the effective mitigation of the inflammatory and ROS microenvironment. Therefore, sEVs-NGL/T therapy provides a promising strategy for the sEV-based therapy in the treatment of SCI by comprehensively regulating the pathological microenvironment.

Symptoms: Unilateral Hearing Loss and Facial Paresis

Symptoms: Unilateral Hearing Loss and Facial Paresis

Cerebroprotein hydrolysate injection is involved in promoting long-term angiogenesis, vessel diameter and density after cerebral ischemia in mice

AimsIn this study, we aimed investigate the impacts of CH-I on angiogenesis, effects for vascular structure changes and long-term neurological recovery after ischemic stroke as well as the potential mechanisms. Main methodsYoung male mice subjected to intraluminal middle cerebral artery occlusion were administrated with CH-I once daily from day 1 to day 14 after stroke. The infarct volume was evaluated by TTC staining at day 7 after stroke. Neurological deficits were measured 1 to 28 days after stroke. Microvascular density, astrocyte coverage, and angiogenesis were assessed by IF, qRT-PCR, and WB at regular intervals after stroke. LSCI and TPMI measured changes in blood flow and vascular density and width from the day after stroke to day 28. Key findingsCompared with the dMCAO group, CH-I treatment significantly improved neurological recovery and reduced the infarct at day 7 after stroke. CH-I treatment increased the expression of the CD31, BrdU+/CD31+ microvessels and GFAP positive vessels in the peri-infarct cortex at day 7 to 28 after stroke. The expression of protein and gene were enhanced in CH-I group. CH-I significantly improved cerebral blood flow at day 7 after stroke. CH-I increased the vascular density and vascular width at day 14 after stroke. SignificanceCH-I has been shown to restore nerve function, reduce the rate of cerebral infarction, increase microvascular density, and promote angiogenesis. CH-I improved cerebral blood flow, protected blood vessels from postoperative stenosis, and improved vascular plasticity.