Neural Regeneration Research最新文献

Nerve stimulation is a rapidly developing field, demonstrating positive outcomes across several conditions. Despite potential benefits, current nerve stimulation devices are large, complicated, and are powered via implanted pulse generators. These factors necessitate invasive surgical implantation and limit potential applications. Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications. However, device miniaturization presents a serious engineering challenge. This review presents significant advancements from several groups that have overcome this challenge and developed millimetric-sized nerve stimulation devices. These are based on antennas, mini-coils, magneto-electric and opto-electronic materials, or receive ultrasound power. We highlight key design elements, findings from pilot studies, and present several considerations for future applications of these devices.

Abstract: Multiple sclerosis is an inflammatory disorder characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Although current first-line therapies can help manage symptoms and slow down disease progression, there is no cure for multiple sclerosis. The gut-brain axis refers to complex communications between the gut flora and the immune, nervous, and endocrine systems, which bridges the functions of the gut and the brain. Disruptions in the gut flora, termed dysbiosis, can lead to systemic inflammation, leaky gut syndrome, and increased susceptibility to infections. The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors, and gut flora may play a pivotal role in regulating immune responses related to multiple sclerosis. To develop more effective therapies for multiple sclerosis, we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis. This review provides an overview of the role of the gut flora in multiple sclerosis.

Abstract: Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.

Abstract: Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age-and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

Abstract: The N-terminal EF-hand calcium-binding proteins 1-3 (NECAB1-3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-beta A4 precursor protein-binding family A members 2 and 3, key regulators of β-amyloid production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not well-characterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein-protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.

Abstract: Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically short-chain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood-brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood-brain barriers, thereby alleviating symptoms of Parkinson's disease.

Abstract: Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury-specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research (in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc (AXER-204), fasudil, phosphatase and tensin homolog protein (PTEN) antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide, (-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.