Explore the vast range of titles available.

Background The Sciatic nerve (SN) exhibits distinct sex and side-related differences, which have significant implications for clinical practice. The study investigated the sex and side-related morphologic and morphometric variations of the nerve using cadavers. Methods This is a cross-sectional cadaveric study involving 62 Ugandan cadavers. Continuous variables were reported using descriptive statistics and discrete variables were reported as percentages. Ordinary two-way ANOVA was used to compare the dimensions and proportion of the patterns of the SN. Results The study identified six categories of exit patterns of the SN, type A (“Below and undivided”) occurred in a majority of cases (62.9%). A penta-furcate branching pattern dominated the whole population. Bifurcate termination pattern was found in most SNs (90.3% and 87.1% for right and left limbs respectively) while the rest have the trifurcate termination pattern, with no side or sex-related variations. The average dimensions of SN were within normal ranges, and showed no side-related differences but with a sex difference (significantly higher in males than females), mean length of the SN in centimetres (length A: Males, right limbs = 30.58  ±  9.00; left limbs = 31.30  ±  6.20; Females, right = 26.07  ±  6.58; left = 26.30  ±  5.56). The difference in the length “A” for the males left limb and females right limb was statistically significant with a p -value of 0.0195. Conclusions Most of the examined SNs showed normal anatomical characteristics with rare cases of sex-related dimorphism in the termination level and morphometry (length and diameter) of the nerve. The observed sexual dimorphisms in sciatic nerves are of clinical and surgical interest; hence, suggesting the need for further investigations in different populations, especially using advanced techniques such as ultrasonography anatomic techniques.

Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1–dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K–phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2–PI3K–p-Akt signalling pathway. Hervera et al. show that extracellular vesicles containing NOX2 complexes are released from macrophages and incorporated into injured axons, leading to axonal regeneration through PI3K–p-Akt signalling.

Sciatic nerve crush injury triggers sterile inflammation within the distal nerve and axotomized dorsal root ganglia (DRGs). Granulocytes and pro-inflammatory Ly6C high monocytes infiltrate the nerve first and rapidly give way to Ly6C negative inflammation-resolving macrophages. In axotomized DRGs, few hematogenous leukocytes are detected and resident macrophages acquire a ramified morphology. Single-cell RNA-sequencing of injured sciatic nerve identifies five macrophage subpopulations, repair Schwann cells, and mesenchymal precursor cells. Macrophages at the nerve crush site are molecularly distinct from macrophages associated with Wallerian degeneration. In the injured nerve, macrophages ‘eat’ apoptotic leukocytes, a process called efferocytosis, and thereby promote an anti-inflammatory milieu. Myeloid cells in the injured nerve, but not axotomized DRGs, strongly express receptors for the cytokine GM-CSF. In GM-CSF-deficient ( Csf2 -/- ) mice, inflammation resolution is delayed and conditioning-lesion-induced regeneration of DRG neuron central axons is abolished. Thus, carefully orchestrated inflammation resolution in the nerve is required for conditioning-lesion-induced neurorepair.

Pycnogenol, a standardized French maritime pine bark extract, is known for its antioxidant, anti-inflammatory, and neuroprotective properties. This study evaluated its therapeutic potential in sciatic nerve regeneration following crush injury in female Sprague Dawley rats. Twenty-one rats were assigned to Sham, Control, and Pycnogenol (100 mg/kg/day) groups. After standardized nerve injury, Pycnogenol was administered for 28 days. Functional recovery was assessed using the Sciatic Functional Index (SFI), pinprick, and cold allodynia tests. Histopathology, muscle weight, and ELISA for nerve growth factor (NGF) were evaluated post-euthanasia. By Day 14, the Pycnogenol group showed significantly better SFI scores (83.60 ± 2.26 vs. 89.81 ± 2.42, p  < 0.001), with continued improvement through Day 28 (49.42 ± 3.0 vs. 62.95 ± 2.93, p  < 0.001). Histological analysis revealed enhanced muscle regeneration, increased fiber area, and improved myelination. ELISA confirmed significantly elevated NGF levels, supporting Pycnogenol’s neuroprotective role. These findings highlight its potential in peripheral nerve injury treatment. Further research is needed to confirm efficacy in humans, explore molecular mechanisms, and compare it with existing neuro-regenerative therapies. Pycnogenol may serve as a promising agent in neurology and regenerative medicine.

Peripheral nerve injury results in limited nerve regeneration and severe functional impairment. Mesenchymal stem cells (MSCs) are a remarkable tool for peripheral nerve regeneration. The involvement of human umbilical cord MSC‐derived extracellular vesicles (hUCMSC‐EVs) in peripheral nerve regeneration, however, remains unknown. In this study, we evaluated functional recovery and nerve regeneration in rats that received hUCMSC‐EV treatment after nerve transection. We observed that hUCMSC‐EV treatment promoted the recovery of motor function and the regeneration of axons; increased the sciatic functional index; resulted in the generation of numerous axons and of several Schwann cells that surrounded individual axons; and attenuated the atrophy of the gastrocnemius muscle. hUCMSC‐EVs aggregated to rat nerve defects, down‐regulated interleukin (IL)‐6 and IL‐1β, up‐regulated IL‐10 and modulated inflammation in the injured nerve. These effects likely contributed to the promotion of nerve regeneration. Our findings indicate that hUCMSC‐EVs can improve functional recovery and nerve regeneration by providing a favourable microenvironment for nerve regeneration. Thus, hUCMSC‐EVs have considerable potential for application in the treatment of peripheral nerve injury.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery. Bioresorbable electronic stimulators can deliver electrical stimulation in rodents to enhance functional muscle recovery after nerve injury. Here, the authors present a bioresorbable dynamic covalent polymer that enables reliable, long-lived operation of soft, stretchable devices of this type.

Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.

Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

Early experimental evidence suggests that predegenerated nerve graft enhance axonal growth compared to freshly harvested nerve graft in nerve gap repair. However, the practicality of surgically pre-conditioning nerves for grafting remains a major obstacle. Herein, we aim to investigate the feasibility of focal lesioning of nerve tissue using high-intensity focused ultrasound (HIFU) and compare the regenerative effects of predegenerated nerve grafts to freshly harvested grafts in a rat sciatic nerve transection and repair model. As a proof of principle, sciatic nerves were exposed for HIFU lesioning to increase targeting accuracy. HIFU induced focal thermal lesioning to the sciatic nerve, resulting in p75 and cJun up-regulation at the distal segment observed at 7 days post-sonication. All behavioural outcome metrics including von Frey sensory test and walking gait were similar between animals with freshly harvested and predegenerated nerve grafts except soleus muscle weight was significantly higher in the latter group. As well, similar axon histomorphometric results were found in 2-week survival animals. Our findings showed that it is possible to induce Wallerian degeneration in distal nerve for grafting using non-invasive HIFU. However, limited beneficial effects of predegenerated grafts were obtained compared to freshly harvested grafts in nerve gap repair.

Motor axon regeneration following peripheral nerve injury is critical for motor recovery but therapeutic interventions enhancing this are not available. We conduct a phenotypic screen on human motor neurons and identified blebbistatin, a non-muscle myosin II inhibitor, as the most effective neurite outgrowth promotor. Despite its efficacy in vitro, its poor bioavailability limits in vivo application. We, therefore, utilize a blebbistatin analog, NMIIi2, to explore its therapeutic potential for promoting axon regeneration. Local NMIIi2 application directly to injured axons enhances regeneration in human motor neurons. Furthermore, following a sciatic nerve crush injury in male mice, local NMIIi2 administration to the axonal injury site facilitates motor neuron regeneration, muscle reinnervation, and functional recovery. NMIIi2 also promotes axon regeneration in sensory, cortical, and retinal ganglion neurons. These findings highlight the therapeutic potential of topical NMII inhibition for treating axon damage. Therapeutic interventions for motor axon regeneration following peripheral nerve injury are currently unavailable. Here authors show local administration of a non-muscle myosin II inhibitor at the injury site increases motor and sensory function recovery in vivo.