Influence of resveratrol release on the tissue response to mechanically adaptive cortical implants

Abstract

The stability and longevity of recordings obtained from intracortical microelectrodes continues to remain an area of concern for neural interfacing applications. The limited longevity of microelectrode performance has been associated with the integrity of the blood brain barrier (BBB) and the neuroinflammatory response to the microelectrode. Here, we report the investigation of an additive approach that targets both mechanical and chemical factors believed to contribute to chronic BBB instability and the neuroinflammatory response associated with implanted intracortical microelectrodes. The implants investigated were based on a mechanically adaptive, compliant nanocomposite (NC), which reduces the tissue response and tissue strain. This material was doped with various concentrations of the antioxidant resveratrol with the objective of local and rapid delivery. In vitro analysis of resveratrol release, antioxidant activity, and cytotoxicity suggested that a resveratrol content of 0.01% was optimal for in vivo assessment. Thus, probes made from the neat NC reference and probes containing resveratrol (NC Res) were implanted into the cortical tissue of rats for up to sixteen weeks. Histochemical analysis suggested that at three days post-implantation, neither materials nor therapeutic approaches (independently or in combination) could alter the initial wound healing response. However, at two weeks post-implantation, the NC Res implant showed a reduction in activated microglia/macrophages and improvement in neuron density at the tissue-implant interface when compared to the neat NC reference. However, sixteen weeks post-implantation, when the antioxidant was exhausted, NC Res and the neat NC reference exhibited similar tissue responses. The data show that NC Res provides short-term, short-lived benefits due to the antioxidant release, and a long-term reduction in neuroinflammation on account of is mechanical adaptive, compliant nature. Together, these results demonstrate that local delivery of resveratrol can provide an additive advantage by providing a consistent reduction in the tissue response.

Microelectrode implantation in motor cortex causes fine motor deficit: Implications on potential considerations to Brain Computer Interfacing and Human Augmentation

“…Because neuroinflammation has the potential to cause detriments in a variety of ways, one focus of our lab is techniques to mitigate neuroinflammation. Successes have been found in methods such as administration of anti-oxidants 47 , 60 , 61 , mechanically compliant implants 62 , reducing vascular damage during implantation 63 , and nanopatterned implants to better mimic native brain architecture 64 . It also must be considered that the current study was carried out on healthy young rats, and not a disease model representing the typical patient population receiving an implant in the brain.…”

Investigating the Association between Motor Function, Neuroinflammation, and Recording Metrics in the Performance of Intracortical Microelectrode Implanted in Motor Cortex

“…Immunohistochemistry was utilized to quantify the tissue reaction for activated microglia, astrocytes, blood–brain barrier permeability, and total neurons directly around the electrode implant site. Standard immunohistochemistry protocols used in our lab were conducted on the sliced brain tissue [ 40 , 41 , 45 ]. Briefly, two frozen slides per animal (each containing three tissue slices from layers III and V of the cortex) were equilibrated to room temperature (RT) for one hour.…”

Use of affinity allows anti‐inflammatory and anti‐microbial dual release that matches suture wound resolution

“…RSV's anti‐inflammatory activity comes from its antioxidant properties, scavenging free radicals involved in inflammation to help prevent chronic inflammation from occurring. A 100 μ M solution of DPPH in ethanol was created, according to published protocol . This DPPH solution was incubated with dual‐loaded pCD coated suture release samples in a 1:1 ratio for 30 min, after which scavenging can be determined by reading color change spectrophotometrically at 517 nm.…”

“…A 100 μM solution of DPPH in ethanol was created, according to published protocol. 46 This DPPH solution was incubated with dualloaded pCD coated suture release samples in a 1:1 ratio for 30 min, after which scavenging can be determined by reading color change spectrophotometrically at 517 nm. A positive control of 1 mg/mL RSV and a negative control of PBS were used to determine % DPPH scavenging.…”

“…In published literature, 5-25 μM (1.14-5.7 μg/mL) has been cited as an effective RSV dosage to modulate inflammation in neural tissue. 46 The completed release shows an (a) (b) average daily release of 1.37 μg/mL [ Fig. 5(a)] from the sutures, which is appropriate for therapeutic effectiveness.…”