Objective: To explore the potential evidence of active peripheral nerve necrosis when n-hexane produces toxic effects on peripheral nerves. Methods: In May 2023, 36 SPF grade SD male rats with a body weight of 200-220 g were divided into 4 groups with 9 rats in each group and given normal saline and different doses of n-hexane (168, 675, 2 700 mg/kg) by gavage for 6 consecutive weeks (5 days/week). Three rats in each group were killed at the 2nd, 4th and 6th week, respectively. The spinal cord to sciatic nerve tissue was broken and the supernatant was extracted for SDS-PAGE protein isolation. The expression level of Sarm1 protein was analyzed with the β-Actin color strip of internal reference protein by Western blot. The expression of Sarm1 protein was analyzed by the gray ratio of the two. At the 6th week, the sciatic nerve sections of the each group were observed by light microscope and electron microscope. Results: The number of axons was obviously reduced by light microscopy. According to electron microscope, myelin lesions were mainly local disintegration, deformation, and different thickness. The deformation of axonal surface became smaller. The axons in the nerve bundle membrane showed degeneration and reduction. The gray ratio of Sarm1 protein and internal reference protein bands in each group had no significant change at the second week of exposure, and the ratio of SARM1 protein to internal reference protein bands was 1.47 in the high dose group at the fourth week, and 1.51 and 1.89 in the middle and high dose group at the sixth week, respectively. Conclusion: Waller\'s degeneration was observed in sciatic neuropathologic manifestations of n-hexane-poisoned rats, and the expression level of Sarm1 protein increased.
目的： 探讨正己烷对大鼠周围神经产生的毒性作用对周围神经主动坏死现象的产生提供潜在证据。 方法： 于2023年5月，选择体重为200~220 g的36只SPF级SD雄性大鼠，随机分成4组，每组9只，对照组、低、中、高剂量组分别予生理盐水、不同剂量正己烷（168、675、2 700 mg/kg）连续6周（5 d/周）灌胃。各组分别于第2、4、6周处死3只大鼠，取大鼠脊髓至坐骨神经组织，破碎、离心并取上清液进行聚丙烯酰胺凝胶电泳（SDS-PAGE）分离蛋白，用Western blot法检测Toll白介素受体基序蛋白1（Sarm1）蛋白表达水平，并与内参蛋白β-Actin显色条带进行灰度分析，以二者灰度比值分析Sarm1蛋白表达情况。第6周各组大鼠坐骨神经光镜、电镜切片进行观察。 结果： 光镜示轴突数量明显减少；电镜示髓鞘病变主要为局部崩解、变形、厚薄不一，轴突腔面变形变小，神经束膜内轴突呈退行、减少表现，高剂量部分轴索呈华勒氏退行性病理表现。各组大鼠染毒Sarm1与内参蛋白显色条带灰度比值第2周无明显变化，第4周高剂量组为1.47，第6周中剂量组和高剂量组分别为1.51、1.89，均为明显表达。 结论： 正己烷中毒大鼠的坐骨神经病理表现中观察到华勒氏退行性病变现象，同时Sarm1蛋白表达水平上升。.

This study aimed to elucidate vincristine (VCR)-induced peripheral neuropathy in aged rats, a poorly understood neurotoxicity. Both young and old Wistar rats were administered VCR (0.1 mg/kg, intraperitoneally (i.p.)) and compared to age-matched controls (0.9% saline; 10 mg/mL, i.p.). Mechanical (MN) and thermal nociceptive (TN) responses were assessed on days 0, 6, 11, and 17. Locomotor response, cognitive ability, and anxious-like behavior were evaluated on days 14, 15, and 16. Results showed MN and TN responses in both young and old VCR-exposed rats. In old rats, VCR exacerbated MN (on days 6, 11, and 17) and TN (on days 6 and 17) responses. VCR also induced cognitive impairments and anxiety-like behavior. Histological analysis revealed Wallerian degeneration in the spinal cords of VCR-exposed rats accompanied by macrophage migration. Furthermore, VCR increased Ca2+-ATPase activity while inhibiting Na+, K+-ATPase activity in young and old rats. VCR altered the homeostasis of Mg2+-ATPase activity. Lipid peroxidation and nitrite and nitrate levels increased in young and old rats exposed to VCR. This study provides valuable insights into VCR\'s mechanistic pathways in aged rats, emphasizing the need for further research in this area.

Neuritin, also known as candidate plasticity gene 15 (CPG15), was first identified as one of the activity-dependent gene products in the brain. Previous studies have been reported that Neuritin induces neuritogenesis, neurite arborization, neurite outgrowth and synapse formation, which are involved in the development and functions of the central nervous system. However, the role of Neuritin in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of Neuritin steering Schwann cell dedifferentiation during Wallerian degeneration (WD) in injured peripheral nerve. Herein, using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that Neuritin vividly accelerates Schwann cell dedifferentiation. Moreover, we found that Neuritin promotes Schwann cell demyelination as well as axonal degeneration, phagocytosis, secretion capacity. In summary, we first described Neuritin acts as a positive regulator for Schwann cell dedifferentiation and WD after peripheral nerve injury.

暂无摘要。

Spinal cord contusion injury results in Wallerian degeneration of spinal cord axonal tracts, which are necessary for locomotor function. Axonal swelling and loss of axonal density at the contusion site, characteristic of Wallerian degeneration, commence within hours of injury. Tempol, a superoxide dismutase mimetic, was previously shown to reduce the loss of spinal cord white matter and improve locomotor function in an experimental model of spinal cord contusion, suggesting that tempol treatment might inhibit Wallerian degeneration of spinal cord axons. Here, we report that tempol partially inhibits Wallerian degeneration, resulting in improved locomotor recovery. We previously reported that Wallerian degeneration is reduced by inhibitors of aldose reductase (AR), which converts glucose to sorbitol in the polyol pathway. We observed that tempol inhibited sorbitol production in the injured spinal cord to the same extent as the AR inhibitor, sorbinil. Tempol also prevented post-contusion upregulation of AR (AKR1B10) protein expression within degenerating axons, as previously observed for AR inhibitors. Additionally, we hypothesized that tempol inhibits axonal degeneration by preventing loss of the glutathione pool due to polyol pathway activity. Consistent with our hypothesis, tempol treatment resulted in greater glutathione content in the injured spinal cord, which was correlated with increased expression and activity of gamma glutamyl cysteine ligase (γGCL; EC 6.3.2.2), the rate-limiting enzyme for glutathione synthesis. Administration of the γGCL inhibitor buthionine sulfoximine abolished all observed effects of tempol administration. Together, these results support a pathological role for polyol pathway activation in glutathione depletion, resulting in Wallerian degeneration after spinal cord injury (SCI). Interestingly, methylprednisolone, oxandrolone, and clenbuterol, which are known to spare axonal tracts after SCI, were equally effective in inhibiting polyol pathway activation. These results suggest that prevention of AR activation is a common target of many disparate post-SCI interventions.

Axons successfully repaired with polyethylene glycol (PEG) fusion tecnology restored axonal continuity thereby preventing their Wallerian degeneration and minimizing muscle atrophy. PEG fusion studies in animal models and preliminary clinical trials involving patients with digital nerve repair have shown promise for this therapeutic approach. PEG fusion is safe to perform, and given the enormous potential benefits, there is no reason not to explore its therapeutic potential.

OBJECTIVE: Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics.
METHODS: This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones.
RESULTS: The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms.
CONCLUSIONS: These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.

Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways. Previously, inflammation was thought to be detrimental to the body, but further research has shown that appropriate inflammation promotes nerve regeneration, axon regeneration, and myelin formation. On the contrary, excessive inflammation can cause nerve tissue damage and pathological changes, and even lead to neurological diseases. Therefore, after nerve injury, various cells in the body interact with cytokines and chemokines to promote peripheral nerve repair and regeneration by inhibiting the negative effects of inflammation and harnessing the positive effects of inflammation in specific ways and at specific times. Understanding the interaction between neuroinflammation and nerve regeneration provides several therapeutic ideas to improve the inflammatory microenvironment and promote nerve regeneration.

OBJECTIVE: After vertical parasagittal hemispherotomy a restricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective cohort study analyses the anatomic site and the time course of the diffusion restriction after vertical parasagittal hemispherotomy.
METHODS: Fifty-nine patients were included into this study, all of them having had one pre-operative and at least one post-operative MRI, including diffusion imaging at b‑values of 0 and 1000 s/mm2 with a calculated ADC.
RESULTS: Diffusion restriction occurred exclusively on the operated site in all patients. In the basal ganglia, diffusion restriction was present in 37 of 38 patients at the first postoperative day with a duration of 38 days. In the midbrain, the posterior limb of the internal capsule and the thalamus, a restricted diffusion became postoperatively prominent at day 9 in all three localizations, with a duration of 36, 34 and 36 days, respectively. The incidence of thalamic lesions was lower if a preoperative damage had occurred.
CONCLUSIONS: The restricted diffusion in the basal ganglia resembles direct effects of the operation at its edges, whereas the later appearing diffusion restriction in the midbrain and the posterior limb of the internal capsule rather belong to a degeneration of the descending fibers being transected by the hemispherotomy in the sense of a Wallerian degeneration. The presence of preoperative hemispheric lesions influences the development of diffusion restriction at subacute fiber degeneration.

Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca2+ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.