Melatonin improves quality and longevity of chronic neural recording

Abstract

The chronic performance of implantable neural electrodes is hindered by inflammatory brain tissue responses, including microglia activation, glial scarring, and neuronal loss. Melatonin (MT) has shown remarkable neuroprotective and neurorestorative effects in treating central nervous system (CNS) injuries and degeneration by inhibiting caspase-1, -3, and -9 activation and mitochondrial cytochrome c release, as well as reducing oxidative stress and neuroinflammation. This study examined the effect of MT administration on the quality and longevity of neural recording from an implanted microelectrode in the visual cortex of mice for 16 weeks. MT (30 mg/kg) was administered via daily intraperitoneal injection for acute (3 days before and 14 days post-implantation) and chronic (3 days before and 16 weeks post-implantation) exposures. During the first 4 weeks, both MT groups showed significantly higher single-unit (SU) yield, signal-to-noise ratio (SNR), and amplitude compared to the vehicle control group. However, after 4 weeks of implantation, the SU yield of the acute treatment group dropped to the same level as the control group, while the chronic treatment group maintained significantly higher SU yield compared to both acute (week 5-16) and control (week 0-16) mice. Histological studies revealed a significant increase in neuronal viability and decrease in neuronal apoptosis around the implanted electrode at week 16 in the chronic group in comparison to control and acute subjects, which is correlated with reduced oxidative stress and increased number of pro-regeneration arginase-1 positive microglia cells. These results demonstrate the potent effect of MT treatment in maintaining a high-quality electrode-tissue interface and suggest that MT promotes neuroprotection possibly through its anti-apoptotic, anti-inflammatory, and anti-oxidative properties.

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

“…Additionally, there was significantly more activated microglia/macrophages ( Figure 2 B), reactive astrocytes ( Figure 2 C), and blood–brain barrier permeability ( Figure 2 D) within the first 50 µm of the electrode site compared to further distances. Increased detection of markers for reactive inflammation and breach to the blood–brain barrier are consistent with many previous studies [ 23 , 29 , 37 , 58 ].…”

“…Unfortunately, few studies have found an association between the relationship of the microelectrode performance and the neuroinflammatory response of the implanted devices. Notably, some studies utilizing therapeutics have indicated that proinflammatory molecules and blood–brain barrier permeability have connections to recording performance and histological outcomes [ 34 , 35 , 36 , 37 ]. More recently, we have demonstrated that implanting microelectrodes in the motor cortex causes immediate and lasting motor deficits.…”

Alterations in Ion Channel Expression Surrounding Implanted Microelectrode Arrays in the Brain

“…While acute alterations in potassium channel expression may be responsible for the shift in synaptic circuitry in vivo, the underpinnings responsible for the shift in ion channel expression will need to be identified in future work. Sources may include reactive signaling cascades initiated by insertion (such as the release of inflammatory cytokines that alter ion channel expression and function) 9,17 , and strategies to modify inflammatory mechanisms have improved long-term recording quality in previous reports 80,81 . This work may provide new insight into mechanisms of tissue reactivity surrounding devices that may contribute to signal loss.…”

Nanoparticle Doped PEDOT for Enhanced Electrode Coatings and Drug Delivery

“…Melatonin is an antioxidant and signaling molecule shown to minimize inflammation after injury. Recent work has demonstrated that melatonin is capable of preserving neuronal health around implanted neural electrodes and maintaining high recording quality over time when systemically administered daily . This finding highly motivates the development of local delivery of melatonin from neural electrodes.…”