Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia giving rise to oligodendrocytes, the myelin forming cells in the central nervous system (CNS). While OPCs are highly proliferating during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated, they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar, a barrier mainly formed by reactive astrocytes, microglia, and the deposition of inhibitory extracellular matrix components. If, on one hand, glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.