ABSTRACT
The field of chemogenetics has rapidly expanded over the last decade, and engineered receptors are currently utilized in the lab to better understand molecular interactions in the nervous system. We propose that chemogenetic receptors can be used for far more than investigational purposes. The potential benefit of adding chemogenetic neuromodulation to the current neurosurgical toolkit is substantial. There are several conditions currently treated surgically, electrically, and pharmacologically in clinic, and this review highlights how chemogenetic neuromodulation could improve patient outcomes over current neurosurgical techniques. We aim to emphasize the need to take these techniques from bench to bedside.
Subject(s)
Neurons , Electrodes , HumansABSTRACT
Nerve guidance conduits (NGCs) have the potential to replace autografts in repairing peripheral nerve injuries, but their efficacy still needs to be improved. The efficacy of NGCs is augmented by neurotrophic factors that promote axon growth and by enzymes capable of degrading molecules that inhibit axon growth. In the current study, two types of NGCs loaded with factors (both neurotrophin-3 and chondroitinase ABC) are constructed and their abilities to repair an 8 mm gap in the rat sciatic nerve are examined. The factors are encapsulated in microparticles made of a phase-change material (PCM) or collagen and then sandwiched between two layers of electrospun fibers. The use of PCM allows to achieve pulsed release of the factors upon irradiation with a near-infrared laser. The use of collagen enables slow, continuous release via diffusion. The efficacy is evaluated by measuring compound muscle action potentials (CMAP) in the gastrocnemius muscle and analyzing the nerve histology. Continuous release of the factors from collagen results in enhanced CMAP amplitude and increased axon counts in the distal nerve relative to the plain conduit. In contrast, pulsed release of the same factors from PCM shows a markedly adverse impact on the efficacy, possibly by inhibiting axon growth.
Subject(s)
Chondroitin ABC Lyase , Peripheral Nerve Injuries , Animals , Axons , Nerve Regeneration , Rats , Sciatic NerveABSTRACT
BACKGROUND: Neurodegenerative diseases and spinal cord injury can affect respiratory function often through motor neuron loss innervating the diaphragm. To reinnervate this muscle, new motor neurons could be transplanted into the phrenic nerve (PN), allowing them to extend axons to the diaphragm. These neurons could then be driven by an optogenetics approach to regulate breathing. This type of approach has already been demonstrated in the peripheral nerves of mice. However, there is no established thoracoscopic approach to PN injection. Also, there is currently a lack of preclinical large animal models of diaphragmatic dysfunction in order to evaluate the efficacy of potential treatments. OBJECTIVE: To evaluate the feasibility of thoracoscopic drug delivery into the PN and to assess the viability of hemidiaphragmatic paralysis in a porcine model. METHODS: Two Landrace farm pigs underwent a novel procedure for thoracoscopic PN injections, including 1 nonsurvival and 1 survival surgery. Nonsurvival surgery involved bilateral PN injections and ligation. Survival surgery included a right PN injection and transection proximal to the injection site to induce hemidiaphragmatic paralysis. RESULTS: PN injections were successfully performed in both procedures. The animal that underwent survival surgery recovered postoperatively with an established right hemidiaphragmatic paralysis. Over the 5-d postoperative period, the animal displayed stable vital signs and oxygenation saturation on room air with voluntary breathing. CONCLUSION: Thoracoscopic targeting of the porcine PN is a feasible approach to administer therapeutic agents. A swine model of hemidiaphragmatic paralysis induced by unilateral PN ligation or transection may be potentially used to study diaphragmatic reinnervation following delivery of therapeutics.
