Dexamethasone Reduces the Foreign Body Reaction to Intraneural Electrode Implants in the Peripheral Nerve of the Rat.

Intraneural electrodes must be in intimate contact with nerve fibers to have a proper function, but this interface is compromised due to the foreign body reaction (FBR). The FBR is characterized by a first inflammatory phase followed by a second anti-inflammatory and fibrotic phase, which results in the formation of a tissue capsule around the implant, causing physical separation between the active sites of the electrode and the nerve fibers. We have tested systemically several anti-inflammatory drugs such as dexamethasone (subcutaneous), ibuprofen and maraviroc (oral) to reduce macrophage activation, as well as clodronate liposomes (intraperitoneal) to reduce monocyte/macrophage infiltration, and sildenafil (oral) as an antifibrotic drug to reduce collagen deposition in an FBR model with longitudinal Parylene C intraneural implants in the rat sciatic nerve. Treatment with dexamethasone, ibuprofen, or clodronate significantly reduced the inflammatory reaction in the nerve in comparison to the saline group after 2 weeks of the implant, whereas sildenafil and maraviroc had no effect on infiltration of macrophages in the nerve. However, only dexamethasone was able to significantly reduce the matrix deposition around the implant. Similar positive results were obtained with dexamethasone in the case of polyimide-based intraneural implants, another polymer substrate for the electrode. These results indicate that inflammation triggers the FBR in peripheral nerves, and that anti-inflammatory treatment with dexamethasone may have beneficial effects on lengthening intraneural interface functionality. Anat Rec, 301:1722-1733, 2018. © 2018 Wiley Periodicals, Inc.

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons.

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo.

Dietary resveratrol prevents Alzheimer's markers and increases life span in SAMP8.

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.