Search bioRxiv⌕ Search

Biology subjects

Rasueva, T.

Publications and source records attributed to Rasueva, T..

3 recordsLinked to original sources

Fusogens for Axon Repair in Spinal Cord and Peripheral Nerve Injuries - Studies, Methods, and Mechanisms (systematic review with meta-analysis)

IntroductionThe exploration of alternative strategies for neural tissue regeneration and repair is giving rise to a novel paradigm in neurosurgery: fusogenic therapy. This approach promises rapid restoration of peripheral nerve and spinal cord function by circumventing Wallerian degeneration and eliminating the delay associated with axonal regrowth. Its potential stems from the capacity of fusogens to induce axonal fusion and achieve immediate membrane sealing, complemented by their pronounced neuroprotective properties. However, experimental data on fusogens and their effects are inconsistent, often contentious, and derived using heterogeneous methodologies. MethodsWe present the first comprehensive systematic review covering nearly four decades of research on fusogens for axonal membrane repair and 26 years of their experimental and clinical application in mammalian and human models for peripheral and central nervous system restoration. The review includes a meta-analysis of fusogen efficacy following traumatic spinal cord and peripheral nerve injuries. ResultsConducted in accordance with the PRISMA 2020 flow protocol and PICO criteria, our analysis incorporates 86 sources, 20 of which were included in the meta-analysis. DiscussionIn summary, we have systematized the prevailing approaches and methods for fusogen application, delineated key contentious issues, and identified promising directions for the development of axonal fusion technology.

neuroscience↗

Fusogen-induced recovery of spinal cord function andmorphology after complete transection

BackgroundSpinal cord injury is a critical issue in neurosurgery, lacking established clinical methods for functional restoration. This study reports the effects of a fusogen sealant, composed of polyethylene glycol and chitosan, in an experimental model of complete spinal cord transection in pigs. ObjectiveTo evaluate the functional and morphological recovery of the spinal cord in an animal model of complete transection following treatment with a polyethylene glycol-chitosan conjugate. Materials and methodsHungarian Mangalica pigs (m = 20.0 {+/-} 2.0 kg, N = 5) underwent complete transection of the thoracic spinal cord, followed by an extended laminectomy and transpedicular fixation. In the experimental group (N = 3), a synthesized gel based on a polyethylene glycol-chitosan conjugate was applied to the spinal gap; the other group (N = 2) served as a control. The postoperative period lasted 60 days and included multi-component rehabilitation. Clinical-functional status was assessed using established neurological scales. In vivo retrograde tracing of the spinal cord was performed using hydroxystilbamidine (FluoroGold). Following the experiment, immunofluorescent histology was conducted using primary antibodies to neurofilament (NF-200), a fluorochrome-conjugated secondary antibody, and the nuclear dye 4,6-diamidino-2-phenylindole (DAPI). The resulting morphology was examined via fluorescence and light microscopy. ResultsControl animals maintained lower paraplegia, anesthesia, and pelvic dysfunction throughout the experiment. In contrast, the experimental group showed positive changes, including the return of sensation from day two. By the end of the study, all animals in this group could assume an upright posture and ambulate on all limbs. These outcomes were statistically significant. Microscopy revealed axons traversing the injury site in the experimental group, whereas control samples showed degenerative post-traumatic changes. ConclusionsThis study demonstrates that a fusogen sealant based on a polyethylene glycol-chitosan conjugate promotes significant morphofunctional recovery after complete spinal cord transection, supporting its therapeutic potential.

neuroscience↗

A phrenic-sparing cephalic reanastomosis model: Acute effects and implications

BackgroundHead transplantation (HT), also known as cephalosomatic anastomosis (CSA), is a surgical procedure proposed as a potential method to extend lifespan in cases of terminal bodily failure. CSA requires a thorough evaluation of each step using appropriate experimental animal models, with pigs being particularly suitable due to their anatomical and physiological similarities to humans. The critical challenge in HT is spinal cord fusion, which current research suggests can be facilitated using fusogens. To refine the technical aspects of the procedure, we conducted head replantation in a pig model using polyethylene glycol (PEG)-chitosan conjugate (Neuro-PEG). In this article, we evaluate the technical aspects of this procedure, the rate of recovery of ventilation after spinal cord fusion, and phrenic sparing in a model of autologous decapitation-reanastomosis in a single swine. MethodsA Hungarian Mangalica pig was submitted to surgical separation of the head while maintaining blood flow to the brain through cannulation of the primary cervical vessels. After cephalic separation, the head was reconnected, and the cervical spinal cord fused. ResultsThe animal was weaned from ventilation after 5 h and kept on spontaneous breathing. The animal regained full consciousness, demonstrated early signs of sensory recovery, and restored brain functions. ConclusionPending further confirmatory studies, a phrenic-sparing cephalic reanastomosis with spinal cord fusion using fusogens has clarified the technical aspects of the procedure. A head replantation model with complete vascular cannulation was developed, resulting in the recovery of spontaneous breathing and brain functions.

bioengineering↗