ABSTRACT
The central nervous system (CNS) plays a central role in the control of sensory and motor functions, and the disruption of its barriers can result in severe and debilitating neurological disorders. Neurotrophins are promising therapeutic agents for neural regeneration in the damaged CNS. However, their penetration across the blood-brain barrier remains a formidable challenge, representing a bottleneck for brain and spinal cord therapy. Herein, a nanocapsule-based delivery system is reported that enables intravenously injected nerve growth factor (NGF) to enter the CNS in healthy mice and nonhuman primates. Under pathological conditions, the delivery of NGF enables neural regeneration, tissue remodeling, and functional recovery in mice with spinal cord injury. This technology can be utilized to deliver other neurotrophins and growth factors to the CNS, opening a new avenue for tissue engineering and the treatment of CNS disorders and neurodegenerative diseases.
Subject(s)
Blood-Brain Barrier/metabolism , Nanocapsules/chemistry , Nerve Growth Factors/pharmacology , Nerve Regeneration/drug effects , Spinal Cord Injuries/drug therapy , Acrylic Resins/chemistry , Animals , Biocompatible Materials/chemistry , Blood-Brain Barrier/ultrastructure , Cross-Linking Reagents/chemistry , Drug Liberation , Injections, Intravenous , Macaca mulatta , Methacrylates/chemistry , Mice, Inbred BALB C , Nerve Growth Factors/administration & dosage , Nerve Growth Factors/blood , Nerve Growth Factors/cerebrospinal fluid , PC12 Cells , Permeability , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/chemistry , Polyesters/chemistry , Rats , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathologyABSTRACT
Although several options are available to address adjacent segment disease (ASD), the most effective surgical treatment has not been determined. In addition, it is important to subdivide ASD into stenosis with or without instability to determine if a decompression alone vs an extension of fusion is necessary. A systematic search of multiple medical reference databases was conducted for studies on surgical treatment of ASD. The primary outcome measures used were radiographic and clinical success rates. Meta-analysis was completed to determine effect summary values, 95% confidence intervals, and Q statistic and I2 values, using the random effects model for heterogeneity. The search yielded 662 studies, of which 657 were excluded. A total of 5 (level IV) studies with a total of 118 patients were included in this review. In 2 studies (46 patients), stenosis without instability was the indication for reoperation for ASD. However, extension of fusion was the modality of choice for the treatment of ASD in all studies. Overall clinical improvement (in back and/or leg pain scores) was noted in 71.3% of patients (95% confidence interval, 37.4-100), while radiographic fusion was noted in 89.3% of patients (95% confidence interval, 51.2-100). Following reoperation for ASD, revision surgery rates ranged from 4.5% to 23.1% at last clinical follow-up. There is variability in the clinical improvement following lumbar fusion for ASD. In addition, little literature exists regarding the optimal treatment options for patients with ASD for stenosis with or without instability. [Orthopedics. 2018; 41(2):e161-e167.].
