Transient receptor potential cation channels subfamily V member 4 (TRPV4) are non-selective cation channels expressed in different cell types of the central nervous system. These channels can be activated by diverse physical and chemical stimuli, including heat and mechanical stress. In astrocytes, they are involved in the modulation of neuronal excitability, control of blood flow, and brain edema formation. All these processes are significantly impaired in cerebral ischemia due to insufficient blood supply to the tissue, resulting in energy depletion, ionic disbalance, and excitotoxicity. The polymodal cation channel TRPV4, which mediates Ca²⁺ influx into the cell because of activation by various stimuli, is one of the potential therapeutic targets in the treatment of cerebral ischemia. However, its expression and function vary significantly between brain cell types, and therefore, the effect of its modulation in healthy tissue and pathology needs to be carefully studied and evaluated. In this review, we provide a summary of available information on TRPV4 channels and their expression in healthy and injured neural cells, with a particular focus on their role in ischemic brain injury.

Astrocytes are responsible for maintaining homoeostasis and cognitive functions through calcium signalling, a process that is altered in brain diseases. Current bioelectronic tools are designed to study neurons and are not suitable for controlling calcium signals in astrocytes. Here, we show that electrical stimulation of astrocytes using electrodes coated with graphene oxide and reduced graphene oxide induces respectively a slow response to calcium, mediated by external calcium influx, and a sharp one, exclusively due to calcium release from intracellular stores. Our results suggest that the different conductivities of the substrate influence the electric field at the cell–electrolyte or cell–material interfaces, favouring different signalling events in vitro and ex vivo. Patch-clamp, voltage-sensitive dye and calcium imaging data support the proposed model. In summary, we provide evidence of a simple tool to selectively control distinct calcium signals in brain astrocytes for straightforward investigations in neuroscience and bioelectronic medicine.

Brain ischemia is a severe condition caused by reduced cerebral blood flow, leading to the disruption of ion gradients in brain tissue. This imbalance triggers spreading depolarizations, which are waves of neuronal and glial depolarization propagating through the gray matter. Microelectrode arrays (MEAs) are essential for real-time monitoring of these electrophysiological processes both in vivo and in vitro, but their sensitivity and signal quality are critical for accurate detection of extracellular brain activity. In this study, we evaluate the performance of a flexible microelectrode array based on gold-coated zinc oxide nanorods (ZnO NRs), referred to as nano-fMEA, specifically for high-fidelity electrophysiological recording under pathological conditions. Acute mouse brain slices were tested under two ischemic models: oxygen–glucose deprivation (OGD) and hyperkalemia. The nano-fMEA demonstrated significant improvements in event detection rates and in capturing subtle fluctuations in neural signals compared to flat fMEAs. This enhanced performance is primarily attributed to an optimized electrode–tissue interface that reduces impedance and improves charge transfer. These features enabled the nano-fMEA to detect weak or transient electrophysiological events more effectively, making it a valuable platform for investigating neural dynamics during metabolic stress. Overall, the results underscore the promise of ZnO NRs in advancing electrophysiological tools for neuroscience research.

Brain ischemia is a serious condition caused by reduced cerebral blood flow, causing disruption of ion gradients in brain tissue. This ionic imbalance induces spreading depolarization—waves of neuronal and glial depolarization propagating through the gray matter. Microelectrode arrays (MEAs) enable real-time monitoring of these dynamics in vivo and in vitro, but their sensitivity and signal quality is critical for detecting extracellular brain activity. This study investigates the response of flexible MEA based on gold-coated Zinc Oxide nanorods (ZnO NRs) - called nano-fMEA, for monitoring neural activity under pathological conditions. Nano-fMEA electromechanical properties are shown and discussed to highlight the superior performance of this platform. Conventional MEAs and nano-fMEAs are evaluated on acute mouse brain slices in two ischemic models: oxygen-glucose deprivation (OGD) and hyperkalemia. The findings reveal that the nano-fMEA significantly improves event detection rates and captures subtle fluctuations in neural activity compared to conventional rigid MEAs. This enhanced sensitivity is attributed to the optimized electrode-tissue interface, which reduces impedance and improves charge transfer. The results indicate that the nano-fMEA is particularly effective in detecting weak or transient signals, making it a valuable tool for studying neural dynamics during metabolic stress. Overall, the research underscores the promise of ZnO NRs in advancing electrophysiological tools for neuroscience applications.