An Open-Source 3D-Printed Hindlimb Stabilization Apparatus for Reliable Measurement of Stimulation-Evoked Ankle Flexion in Rat.

Currently there are numerous methods to evaluate peripheral nerve stimulation interfaces in rats, with stimulation-evoked ankle torque being one of the most prominent. Commercial rat ankle torque measurement systems and custom one-off solutions have been published in the literature. However, commercial systems are proprietary and costly and do not allow for customization. One-off lab-built systems have required specialized machining expertise, and building plans have previously not been made easily accessible. Here, detailed building plans are provided for a low-cost, open-source, and basic ankle torque measurement system from which additional customization can be made. A hindlimb stabilization apparatus was developed to secure and stabilize a rat's hindlimb, while allowing for simultaneous ankle-isometric torque and lower limb muscle electromyography (EMG). The design was composed mainly of adjustable 3D-printed components to accommodate anatomical differences between rat hindlimbs. Additionally, construction and calibration procedures of the rat hindlimb stabilization apparatus were demonstrated in this study. In vivo torque measurements were reliably acquired and corresponded to increasing stimulation amplitudes. Furthermore, implanted leads used for intramuscular EMG recordings complemented torque measurements and were used as an additional functional measurement in evaluating the performance of a peripheral nerve stimulation interface. In conclusion, an open-source and noninvasive platform, made primarily with 3D-printed components, was constructed for reliable data acquisition of evoked motor activity in rat models. The purpose of this apparatus is to provide researchers a versatile system with adjustable components that can be tailored to meet user-defined experimental requirements when evaluating motor function of the rat hindlimbs.

Platelets and hemostatic proteins are co-localized with chronic neuroinflammation surrounding implanted intracortical microelectrodes.

Intracortical microelectrodes induce vascular injury upon insertion into the cortex. As blood vessels rupture, blood proteins and blood-derived cells (including platelets) are introduced into the 'immune privileged' brain tissues at higher-than-normal levels, passing through the damaged blood-brain barrier. Blood proteins adhere to implant surfaces, increasing the likelihood of cellular recognition leading to activation of immune and inflammatory cells. Persistent neuroinflammation is a major contributing factor to declining microelectrode recording performance. We investigated the spatial and temporal relationship of blood proteins fibrinogen and von Willebrand Factor (vWF), platelets, and type IV collagen, in relation to glial scarring markers for microglia and astrocytes following implantation of non-functional multi-shank silicon microelectrode probes into rats. Together with type IV collagen, fibrinogen and vWF augment platelet recruitment, activation, and aggregation. Our main results indicate blood proteins participating in hemostasis (fibrinogen and vWF) persisted at the microelectrode interface for up to 8-weeks after implantation. Further, type IV collagen and platelets surrounded the probe interface with similar spatial and temporal trends as vWF and fibrinogen. In addition to prolonged blood-brain barrier instability, specific blood and extracellular matrix proteins may play a role in promoting the inflammatory activation of platelets and recruitment to the microelectrode interface. STATEMENT OF SIGNIFICANCE: Implanted microelectrodes have substantial potential for restoring function to people with paralysis and amputation by providing signals that feed into natural control algorithms that drive prosthetic devices. Unfortunately, these microelectrodes do not display robust performance over time. Persistent neuroinflammation is widely thought to be a primary contributor to the devices' progressive decline in performance. Our manuscript reports on the highly local and persistent accumulation of platelets and hemostatic blood proteins around the microelectrode interface of brain implants. To our knowledge neuroinflammation driven by cellular and non-cellular responses associated with hemostasis and coagulation has not been rigorously quantified elsewhere. Our findings identify potential targets for therapeutic intervention and a better understanding of the driving mechanisms to neuroinflammation in the brain.

Characterization of a Temporary Peripheral Nerve Stimulation Electrode Utilizing a Bioabsorbable Suture Substrate.

Electrical stimulation after peripheral nerve injury (PNI) has the potential to promote more rapid and complete recovery of damaged fiber tracts. While permanently implanted devices are commonly used to treat chronic or persistent conditions, they are not ideal solutions for transient medical therapies due to high costs, increased risk of surgical injury, irritation, infection, and persistent inflammation at the site of the implant. Furthermore, removal of temporary leads placed on or around peripheral nerves may have unacceptable risk for nerve injury, which is counterproductive in developing therapies for PNI treatment. Transient devices which provide effective clinical stimulation while being capable of harmless bioabsorption may overcome key challenges in these areas. However, current bioabsorbable devices are limited in their robustness and require complex fabrication strategies and novel materials which may complicate their clinical translation pathway. In this study, we present a simple bioabsorbable / biodegradable electrode fabricated by modifying standard absorbable sutures, and we present data characterizing our prototype's stability in vitro and in vivo.

Renal Nerve Activity and Arterial Depressor Responses Induced by Neuromodulation of the Deep Peroneal Nerve in Spontaneously Hypertensive Rats.

Hypertension is a main cause of death in the United States with more than 103 million adults affected. While pharmacological treatments are effective, blood pressure (BP) remains uncontrolled in 50-60% of resistant hypertensive subjects. Using a custom-wired miniature electrode, we previously reported that deep peroneal nerve stimulation (DPNS) elicited acute cardiovascular depressor responses in anesthetized spontaneously hypertensive rats (SHRs). Here, we further study this effect by implementing a wireless system and exploring different stimulation parameters to achieve a maximum depressor response. Our results indicate that DPNS consistently induces a reduction in BP and suggests that renal sympathetic nerve activity (RSNA) is altered by this bioelectronic treatment. To test the acute effect of DPNS in awake animals, we developed a novel miniaturized wireless microchannel electrode (w-µCE), with a Z-shaped microchannel through which the target nerves slide and lock into the recording/stimulation chamber. Animals implanted with w-µCE and BP telemetry systems for 3 weeks showed an average BP of 150 ± 14 mmHg, which was reduced significantly by an active DPNS session to 135 ± 8 mmHg (p < 0.04), but not in sham-treated animals. The depressor response in animals with an active w-µCE was progressively returned to baseline levels 14 min later (164 ± 26 mmHg). This depressor response was confirmed in restrained fully awake animals that received DPNS for 10 days, where tail-cuff BP measurements showed that systolic BP in SHR lowered 10% at 1 h and 16% 2 h after the DPNS when compared to the post-implantation baseline. Together, these results support the use of DPN neuromodulation as a possible strategy to lower BP in drug-resistant hypertension.