Spinal cord injury (SCI) is a serious medical condition. The search for an effective cure remains a persistent challenge. Current treatments, unfortunately, are unable to sufficiently improve neurological function, often leading to lifelong disability. This systematic review and meta-analysis evaluated the effectiveness of stem cell therapy for SCI using canine models. It also explored the optimal protocol for implementing stem cell therapy. A comprehensive search of studies was conducted from 2000 to October 2022. This study focused on five outcomes: motor function score, histopathology, IHC, western blot, and SEP. The results demonstrated a significant improvement in locomotion post-SCI in dogs treated with stem cell therapy. The therapy also led to an average increase of 3.15 points in the Olby score of the treated dogs compared to the control group. These findings highlights stem cell therapy\'s potential as a promising SCI treatment. The meta-analysis suggests that using bone marrow stem cells, undergoing neural differentiation in vitro, applying a surgical implantation or intrathecal route of administration, associating matrigel in combination with stem cells, and a waiting period of two weeks before starting treatment can enhance SCI treatment effectiveness.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a transmembrane protein that, when cleaved by metalloproteases through a process called ectodomain shedding, binds to the EGF receptor (EGFR), activating downstream signaling. The HB-EGF/EGFR pathway is crucial in development and is involved in numerous pathophysiological processes. In this issue of The FEBS Journal, Sireci et al. reveal a previously unexplored function of the HB-EGF/EGFR pathway in promoting neuronal progenitor proliferation and sensory neuron regeneration in the zebrafish olfactory epithelium in response to injury.

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small in number and restricted to the sub-ventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, and the olfactory epithelium, is a gift of evolution for the adaptive brain function which requires persistent plastic changes of these regions. It is known that most adult NSCs are latent, showing long cell cycles. In the past decade, the concept of quiescent NSCs (qNSCs) has been widely accepted by researchers in the field, and great progress has been made in the biology of qNSCs. Although the spontaneous neuronal regeneration derived from adult NSCs is not significant, understanding how the behaviors of qNSCs are regulated sheds light on stimulating endogenous NSC-based neuronal regeneration. In this review, we mainly focus on the recent progress of the developmental origin and regulatory mechanisms that maintain qNSCs under normal conditions, and that mobilize qNSCs under pathological conditions, hoping to give some insights for future study.

Traumatic brain injuries(TBI) pose significant challenges to human health, specifically neurological disorders and related motor activities. After TBI, the injured neuronal tissue is known for hardly regenerated and recovered to their normal neuron physiology and tissue compositions. For this reason, tissue engineering strategies that promote neuronal regeneration have gained increasing attention. This study explored the development of a novel neural tissue regeneration cryogel by combining brain-derived decellularized extracellular matrix (ECM) with heparin sulfate crosslinking that can perform nerve growth factor (NGF) release ability. Morphological and mechanical characterizations of the cryogels were performed to assess their suitability as a neural regeneration platform. After that, the heparin concnentration dependent effects of varying NGF concentrations on cryogel were investigated for their controlled release and impact on neuronal cell differentiation. The results revealed a direct correlation between the concentration of released NGF and the heparin sulfate ratio in cryogel, indicating that the cryogel can be tailored to carry higher loads of NGF with heparin concentration in cryogel that induced higher neuronal cell differentiation ratio. Furthermore, the study evaluated the NGF loaded cryogels on neuronal cell proliferation and brain tissue regeneration in vivo. The in vivo results suggested that the NGF loaded brain ECM derived cryogel significantly affects the regeneration of brain tissue. Overall, this research contributes to the development of advanced neural tissue engineering strategies and provides valuable insights into the design of regenerative cryogels that can be customized for specific therapeutic applications.

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries.

Spinal cord injuries are very common worldwide, leading to permanent nerve function loss with devastating effects in the affected patients. The challenges and inadequate results in the current clinical treatments are leading scientists to innovative neural regenerative research. Advances in nanoscience and neural tissue engineering have opened new avenues for spinal cord injury (SCI) treatment. In order for designed nerve guidance conduit (NGC) to be functionally useful, it must have ideal scaffold properties and topographic features that promote the linear orientation of damaged axons. In this study, it is aimed to develop channeled polycaprolactone (PCL)/Poly-D,L-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, modify their surfaces by IKVAV pentapeptide/gold nanoparticles (AuNPs) or polypyrrole (PPy) and investigate the behavior of motor neurons on the designed scaffold surfaces in vitro under static/bioreactor conditions. Their potential to promote neural regeneration after implantation into the rat SCI by shaping the film scaffolds modified with neural factors into a tubular form is also examined. It is shown that channeled groups decorated with AuNPs highly promote neurite orientation under bioreactor conditions and also the developed optimal NGC (PCL/PLGA G1-IKVAV/BDNF/NGF-AuNP50) highly regenerates SCI. The results indicate that the designed scaffold can be an ideal candidate for spinal cord regeneration.

The progression of diabetes frequently results in a myriad of neurological disorders, including ischemic stroke, depression, blood-brain barrier impairment, and cognitive dysfunction. Notably, diabetes-associated cognitive impairment, a prevalent comorbidity during the course of diabetes, progressively affects patients\' cognitive abilities and may reciprocally influence diabetes management, thereby severely impacting patients\' quality of life. Extracellular vesicles, particularly nanoscale exosomes, have garnered considerable attention in recent years. These exosomes carry and transfer various functional molecules, such as proteins, lipids, and diverse non-coding RNAs, serving as novel regulators and communicators in intercellular interactions. Of particular interest, mesenchymal stem cell-derived exosomes (MSC-Exos) have been reported to traverse the blood-brain barrier and ameliorate intracerebral pathologies. This review elucidates the role of MSC-Exos in diabetes-related cognitive impairment, with a focus on their applications as biomarkers, modulation of neuronal regeneration and synaptic plasticity, anti-inflammatory properties, antioxidative effects, and their involvement in regulating the functionality of β-amyloid proteins during the course of cognitive impairment. The immense therapeutic potential of MSC-Exos in the treatment of diabetes-induced cognitive dysfunction is emphasized.

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Alzheimer\'s disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. The Morris water maze (MWM) and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved. In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid β (Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated Aβ phagocytosis, promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.

Drug delivery for the treatment of neurological disorders has long been considered complex due to difficulties in ensuring the drug targeting on a specific site of the damaged neural tissues and its prolonged release. A syringe-injectable polymeric hydrogel with mechanical moduli matching those of brain tissues can provide a solution to deliver the drugs to the specific region through intracranial injections in a minimally invasive manner. In this study, an injectable therapeutic hydrogel with antioxidant pomegranate polyphenols, punicalagin, is reported for efficient neuronal repair. The hydrogels composed of tyramine-functionalized hyaluronic acid and collagen crosslinked by enzymatic reactions have great injectability with high shape fidelity and effectively encapsulate the polyphenol therapeutics. Furthermore, the punicalagin continuously released from the hydrogels over several days could enhance the growth and differentiation of the neurons. Our findings for efficacy of the polyphenol therapeutic-encapsulated injectable hydrogels on neuronal regeneration would be promising for designing a new type of antioxidative biomaterials in brain disorder therapy.