Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

Abstract

Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) ( NGF /PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF /PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF /PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF /PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF /PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.

Protective functions of salvianolic acid B in PC-12 cells against hydrogen peroxide-triggered damage by mediation of microRNA-26a

“…SCI injury can be split into three phases: the acute, secondary and chronic injury processes [4]. Currently, drug and surgical treatments are the main therapeutic strategies for SCI [5], nevertheless, the side effects of these treatments are inevitable. In various researches, local oxidative damage has been reported to occur after SCI [6,7].…”

Targeted delivery of reduced graphene oxide nanosheets using multifunctional ultrasound nanobubbles for visualization and enhanced photothermal therapy

“…22 Recently, ultrasound-targeted NB destruction (UTND), as a safe and effective method, has been able to destruct contrast agents in ultrasound-irradiated locations, which plays a substantial role in improving the efficient delivery of exogenous genes and drugs noninvasively by sonoporation of NBs. 22,23,25,26 As a result, a novel contrast agent having a combination of rGO sheets with NBs can be synthesized, which has both ultrasound molecular imaging and photothermal capabilities; thus allowing monitoring of the PTT process in real time.…”

Holistic Approach to Axonal Regeneration in Cases of Spinal Cord Injury

“…Tuinstra et al further established a multichannel bridge coating which was capable of delivering neurotrophin encoding lentiviruses to promote axonal regeneration following SCI [90]. Ideally, artificial tissue engineering techniques are meant to coat neural multichannel bridges with Schwann cells and macrophages, growth factors and neurotrophic factors, and an extracellular matrix in order to stimulate axonal growth and movement [54,64,91]. In summary, researchers should seek to improve the efficacy of SCI treatment, combined with the simultaneous transplantation of stem cells, by developing techniques which guide the regrowth of nerve cells.…”