Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.

Biofilms are gelatinous masses of microorganisms attached to wound surfaces. Previous studies suggest that biofilms generate resistance towards antibiotic treatments. It was reported that hydrogels containing xylitol and antibiotic combinations produced additive antibiofilm inhibition. However, hydrogel formulations lack specificity, due to which xylitol cannot penetrate into the biofilm matrix and gets easily degraded by bacterial beta lactamase enzymes. It was hypothesized that the incorporation of xylitol in PLGA (polylactic-co-glycolic acid) nanoparticles will enhance penetration into the EPS (extra polymeric substance) component of the biofilm matrix and potentially overcome the antibiotic resistance associated with the biofilms. The purpose of this study was to develop PLGA nanoparticles loaded with xylitol, which will enhance bacterial biofilm penetration. The nanoparticles were loaded with different amounts of xylitol (0.5–5% w/w) and characterized for physiochemical and drug release properties. The metabolic antibiofilm activity of the PLGA nanoparticles containing xylitol was demonstrated by an XTT assay using as references the cultures of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) and the polymicrobial biofilms of both bacterial strains. Live/dead viability staining was also performed to investigate the viability ratio of bacterial cells present in the biofilms. The biofilm penetration study of the PLGA nanoparticles was assessed by combining the nanoparticles with conjugated concanavalin A (Con A)-fluorescein isothiocyanate (FITC) and by viewing using confocal laser scanning electron microscopy (CLSM). In conclusion, the PLGA nanoparticles loaded with xylitol were successfully developed and were found to promote the antibiofilm activity of xylitol in infected wounds.

Background: Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method. Methods: In this study, 0.05 mM KA was administered at dose of 10 µL/100 g body weight, at a rate of 10 µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher. Results: This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment. Conclusions: Kainic acid intra-spinal injection at the concentration of 0.05 mM, and rate 10 µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

Spinal cord injury (SCI) is severe damage to part of the central nervous system (CNS) that can result in impaired sensory and motor function, significantly impacting the quality of life for patients and creating a substantial economic burden on society. The process of SCI involves both primary and secondary injury, with the latter being a series of heightened responses triggered by the initial damage. The complex nature of SCI’s pathological mechanisms has made it challenging to develop effective treatment strategies in clinical settings. Small extracellular vesicles (sEVs) are membrane-bound vesicles with a size range of ≤ 200 nm, released from cells into extracellular spaces. These vesicles are heterogeneous and can originate from various intracellular compartments, including endosomal and non-endosomal sources. A growing body of evidence points to the potential of sEVs in repairing SCI. This review explores the preparation, functions, routes of administration, advantages, challenges, and advanced therapies for sEVs. It also examines the mechanisms through which various types of sEVs can promote healing in SCI and assesses the effectiveness of combining sEVs with other treatment approaches. Furthermore, the review discusses the opportunities and obstacles associated with using sEVs to repair SCI.

Background Nerve injuries initiate a complex immune response that is crucial for triggering repairprocesses but can also exacerbate tissue damage if dysregulated. A tightly regulated balancebetween pro-inflammatory and anti-inflammatory signals is essential for optimal nerveregeneration, as excessive or prolonged inflammation can impede repair, while insufficientimmune activation may delay debris clearance and regeneration. Purpose This review aims to examine the roles of key immune cells, including macrophages,neutrophils, T cells, and B cells exert diverse roles in this process, orchestrating the inflammatoryenvironment and promoting tissue remodeling. Central to their function is metabolicreprogramming, which dictates immune cell activation, phenotype, and regenerative capacity. Method Relevant literature on immune responses and metabolic regulation in nerve injury wasanalyzed to explore how shifts between glycolysis, oxidative phosphorylation, and fatty acidoxidation govern the balance between inflammatory and reparative states. Macrophages displayremarkable functional plasticity, transitioning from pro-inflammatory (M1-like) to proregenerative(M2-like) phenotypes in response to metabolic and microenvironmental cues.Emerging therapeutic strategies aim to harness this immune-metabolic plasticity to improveoutcomes after nerve injury. Results Evidence suggests that metabolic reprogramming is a critical determinant of immune cellbehavior in nerve repair. Interventions such as small-molecule modulators, metabolicglycoengineering, and targeted delivery systems are being explored to fine-tune immune cellmetabolism and restore inflammatory balance. However, challenges remain in achieving cell-typespecificity, managing the intricacies of the immune milieu, and ensuring safe and effective clinicaltranslation. This review examines the cellular and metabolic mechanisms underlying immunemediatednerve repair, highlights the critical importance of inflammatory balance in determiningregenerative outcomes, and discusses promising metabolic targets and therapeutic approaches. Conclusion Understanding the interplay between immune responses and cellular metabolismoffers promising opportunities to enhance nerve regeneration. Advances in immunometabolismmay facilitate the development of precision therapeutic strategies aimed at optimizinginflammatory balance and improving functional recovery following nerve injury.