Biology subjects

Castagnola, E.

Publications and source records attributed to Castagnola, E..

5 recordsLinked to original sources

bioRxiv2026

On-demand, reversible blood-brain barrier opening via electrical activation of piezoelectric nanoparticles for targeted brain drug delivery

Delivering therapeutics to the brain remains one of the most persistent challenges in medicine, because the blood-brain barrier (BBB) excludes over 98% of small-molecule drugs and virtually all biologics from the central nervous system (CNS). We developed electrical BBB modulation (eBBB), an on-demand platform combining vascular-targeting poly-L-lactic acid nanoparticles with high-definition transcranial direct current stimulation to achieve spatially and temporally controlled BBB opening. eBBB produced localized, reversible increases in BBB permeability confined to the stimulated cortex, with the opening area tunable via electrode geometry. This transient window enhanced regional delivery of a small-molecule drug, full-length immunoglobulins, and adeno-associated viral vectors, which are cargo classes otherwise completely excluded by the intact BBB. Neurovascular unit architecture was preserved with no lasting histological damage. Integrating a biodegradable nanomaterial with a clinically evaluated stimulation technology, eBBB offers a programmable, minimally invasive strategy for regional CNS drug delivery across brain malignancies and neurological disorders. One sentence summaryElectrical activation of piezoelectric nanoparticles reversibly opens the blood-brain barrier for minimally invasive drug delivery to targeted cortical regions.

bioengineering↗

bioRxiv2024

Posture-dependent modulation of marmoset cortical motor maps detected via rapid multichannel epidural stimulation

In this study, rapid topographical changes were detected in the forelimb motor maps in the primary motor cortex (M1) of awake marmoset monkeys using our previously developed accurate short-time stimulation mapping procedure (Takemi et al. 2017; Kosugi et al. 2018). The results revealed that although the hotspot (the location in M1 that elicited a forelimb muscle twitch with the lowest stimulus intensity) remained constant across postures, the stimulus intensity required to elicit the forelimb muscle twitch in the perihotspot region and the size of motor representations were posture-dependent. Hindlimb posture was particularly effective in inducing these modulations. The angle of the body axis relative to the gravitational vertical line did not alter the motor maps. These results provide a proof of concept that a rapid stimulation mapping system with chronically implanted cortical electrodes can capture the dynamic regulation of forelimb motor maps in natural conditions. The flexible nature of the motor maps necessitates the reconsideration of the results of motor control and neuroplasticity studies. Neural mechanisms regulating forelimb muscle representations in M1 by the hindlimb sensorimotor state warrant further exploration.

neuroscience↗

bioRxiv2023

Real-time in vivo thoracic spinal glutamate sensing reveals spinal hyperactivity during myocardial ischemia

Myocardial ischemia-reperfusion (IR) can cause ventricular arrhythmias and sudden cardiac death via sympathoexcitation. The spinal cord neural network is crucial in triggering these arrhythmias and evaluating its neurotransmitter activity during IR is critical for understanding ventricular excitability control. To assess the real-time in vivo spinal neural activity in a large animal model, we developed a flexible glutamate-sensing multielectrode array. To record the glutamate signaling during IR injury, we inserted the probe into the dorsal horn of the thoracic spinal cord at the T2-T3 where neural signals generated by the cardiac sensory neurons are processed and provide sympathoexcitatory feedback to the heart. Using the glutamate sensing probe, we found that the spinal neural network was excited during IR, especially after 15 mins, and remained elevated during reperfusion. Higher glutamate signaling was correlated with the reduction in the cardiac myocyte activation recovery interval, showing higher sympathoexcitation, as well as dispersion of the repolarization which is a marker for increased risk of arrhythmias. This study illustrates a new technique for measuring the spinal glutamate at different spinal cord levels as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/531911v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@d2e503org.highwire.dtl.DTLVardef@1b93bdeorg.highwire.dtl.DTLVardef@99ceaorg.highwire.dtl.DTLVardef@11d053e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

Real-time multi-channel measurements of tonic serotonin (5-hydroxytryptamine, 5-HT) concentrations across different brain regions are of utmost importance to the understanding of 5-HTs role in anxiety, depression, and impulse control disorders, which will improve the diagnosis and treatment of these neuropsychiatric illnesses. Chronic sampling of 5-HT is critical in tracking disease development as well as the time course of pharmacological treatments. Despite their value, in vivo chronic multi-site measurements of 5-HT have not been reported. To fill this technological gap, we batch fabricated implantable glassy carbon (GC) microelectrode arrays (MEAs) on a flexible SU-8 substrate to provide an electrochemically stable and biocompatible device/tissue interface. Then, to achieve multi-site detection of tonic 5-HT concentrations, we incorporated the poly(3,4-ethylenedioxythiophene)/functionalized carbon nanotube (PEDOT/CNT) coating on the GC microelectrodes in combination with a new square wave voltammetry (SWV) approach, optimized for selective 5-HT measurement. In vitro, the PEDOT/CNT coated GC microelectrodes achieved high sensitivity towards 5-HT, good fouling resistance in the presence of 5-HT, and excellent selectivity towards the most common neurochemical interferents. In vivo, our PEDOT/CNT-coated GC MEAs were able to successfully detect basal 5-HT concentrations at different locations of the CA2 hippocampal region of mice in both anesthetized and awake head-fixed conditions. Furthermore, the implanted PEDOT/CNT-coated MEA achieved stable detection of tonic 5-HT concentrations for one week. Finally, histology data in the hippocampus shows reduced tissue damage and inflammatory responses compared to stiff silicon probes. To the best of our knowledge, this PEDOT/CNT-coated GC MEA is the first implantable flexible multisite sensor capable of chronic in vivo multi-site sensing of tonic 5-HT. This implantable MEA can be custom-designed according to specific brain region of interests and research questions, with the potential to combine electrophysiology recording and multiple analyte sensing to maximize our understanding of neurochemistry. HighlightsO_LIPEDOT/CNT-coated GC microelectrodes enabled sensitive and selective tonic detection of serotonin (5-HT) using a new square wave voltammetry (SWV) approach C_LIO_LIPEDOT/CNT-coated GC MEAs achieved multi-site in vivo 5-HT tonic detection for one week. C_LIO_LIFlexible MEAs lead to reduced tissue damage and inflammation compared to stiff silicon probes. C_LI

bioengineering↗

bioRxiv2022

Integrated microprism and micro-electrode array for chronic in vivo two-photon imaging and electrophysiology across all cortical layers

Electrophysiology is a vital tool in neuroscience research with increasing translational value. It is used to record or modulate neuronal activity with high temporal but lower spatial resolution. Optical technologies, such as two-photon microscopy (TPM) can complement electrophysiological recordings with large-scale imaging at cellular resolution. Combining these two provides a powerful platform to elucidate and coordinate multimodal functions. Prior attempts have been limited to the superficial brain from a top-down optical view. Here, we describe a novel combination of transparent microelectrode arrays (MEAs) with glass microprisms for simultaneous electrophysiology and optical imaging of all cortical layers in a vertical plane. We tested our device in Thy1-GCaMP6 mice for over 4 months and demonstrated its capability for multisite single-unit recording, microstimulation, and simultaneous TPM calcium imaging. Using this setup, we reveal how amplitude, frequency, and depth of microstimulation impact neural activation patterns across the cortical column. This work presents a multimodal tool that extends integrated electrophysiology and optical imaging from the superficial brain to the whole cortical column, opening new avenues of neuroscience research and neurotechnology development.

bioengineering↗