Biology subjects

Airan, R.

Publications and source records attributed to Airan, R..

4 recordsLinked to original sources

bioRxiv2026

Ultrasonic local anesthetic uncaging enables noninvasive, targeted, and transient knock-out of brain function

Noninvasive, spatially localized brain inhibition would enable precise neural circuit interrogation, mapping, and treatment. We previously presented SonoRopi, an acoustically activatable liposomal formulation of ropivacaine, and demonstrated its utility for targeted peripheral nerve anesthesia. Here, we extend SonoRopi to localized brain anesthesia following intravenous administration and transcranial focused ultrasound application. Ultrasonic uncaging of SonoRopi releases ropivacaine, which crosses the intact blood-brain barrier to anesthetize the sonicated region. SonoRopi uncaging in mouse primary visual cortex suppressed visually evoked cortical activity for one hour, while uncaging in rat somatosensory hindlimb cortex produced lateralized, reversible hindlimb sensory anesthesia. Off-target control sonication preserved function in both paradigms. No acute histologic injury or open-field behavioral abnormalities were detected following this intervention. SonoRopi thereby enables noninvasive, spatially targeted, reversible brain inhibition with physiologic and behavioral efficacy in two rodent species.

bioengineering↗

bioRxiv2026

Ultrasonic potentiation of ketamine neuromodulation

The psychiatric utility of ketamine is limited by its dissociative and systemic side effects. Recently, to enable precision ketamine pharmacotherapy, we introduced SonoKet, ketamine-loaded acoustically activatable liposomes that enable focused ultrasound (FUS)-targeted ketamine delivery to millimeter-sized brain regions. In initial studies, we observed that SonoKet uncaging targeted ketamine to the ultrasound-treated brain region, while inducing greater electrophysiologic and behavioral functional effects than dose-matched free ketamine. To further define these uncaging-potentiated neuromodulatory effects, we used solid-phase microextraction (SPME) coupled to LC-MS/MS to investigate the effect of ultrasound and SonoKet uncaging on key neurotransmitters in real-time. SPME probes were used to sample ketamine, its metabolites, and glutamate, GABA, serotonin (5-HT), and dopamine in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and retrosplenial cortex (RsC) of awake rats. Sampling occurred before and after intravenous administration of either SonoKet, free ketamine, or saline, with FUS targeted to either a frontolimbic or caudal brain region. FUS alone did not yield significant changes in neurotransmitter concentration, nor did it affect the pharmacodistribution of free ketamine. In contrast, FUS generally increased the neurotransmitter response to free ketamine, suggesting an ultrasonic potentiation of ketamine neuromodulation. SonoKet (0.75 mg/kg) uncaging with FUS elicited further elevations in glutamate, GABA, and 5-HT within the FUS-targeted region, along with an increase in dopamine in the NAc when the frontolimbic region was sonicated. These increases were similar to or higher than those induced by 10 mg/kg free ketamine alone or 0.75 mg/kg free ketamine combined with FUS, especially with frontolimbic SonoKet uncaging. Altogether, FUS potentiates ketamine-induced neuromodulation, with spatially specific and synergistically greater effects when ketamine is spatially localized via ultrasonic uncaging. This strategy could augment ketamine pharmacotherapy for psychiatric diseases, while limiting its dissociative and abuse liabilities. HighlightsO_LIFocused ultrasound potentiated ketamine-driven glutamate, serotonin, and dopamine release C_LIO_LILocalized ketamine delivery with SonoKet uncaging drove synergistically greater region-specific neurochemical responses C_LIO_LIUncaging boosts ketamine effects at a fraction of the ketamine dose C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/741494v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@15c75c8org.highwire.dtl.DTLVardef@138d06eorg.highwire.dtl.DTLVardef@fc0c56org.highwire.dtl.DTLVardef@18e233b_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2024

Ultrasonic cerebrospinal fluid clearance improves outcomes in hemorrhagic brain injury models

Introduction (Abstract)Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates the removal of pathogenic substances from the cerebrospinal fluid (CSF) and the brain interstitium. This protocol clears neurofilament light chain (NfL) - an aging byproduct - in aged mice and clears red blood cells (RBCs) from the central nervous system in two mouse models of hemorrhagic brain injury. Cleared RBCs accumulate in the cervical lymph nodes from both the CSF and interstitial compartments, indicating clearance through meningeal lymphatics. Treating these hemorrhagic brain injury models with this ultrasound protocol reduced neuroinflammatory and neurocytotoxic profiles, improved behavioral outcomes, decreased morbidity and, importantly, increased survival. RBC clearance efficacy was blocked by mechanosensitive channel antagonism and was effective when applied in anesthetized subjects, indicating a mechanosensitive channel mediated mechanism that does not depend on sensory stimulation or a specific neural activity pattern. Notably, this protocol qualifies for an FDA non-significant risk designation given its low intensity, making it readily clinically translatable. Overall, our results demonstrate that this low-intensity transcranial focused ultrasound protocol clears hemorrhage and other harmful substances from the brain via the meningeal lymphatic system, potentially offering a novel therapeutic tool for varied neurologic disorders.

bioengineering↗

bioRxiv2020

Deep-fUS: functional ultrasound imaging of the brain using deep learning and sparse data

Functional ultrasound (fUS) is a rapidly emerging modality that enables whole-brain imaging of neural activity in awake and mobile rodents. To achieve sufficient blood flow sensitivity in the brain microvasculature, fUS relies on long ultrasound data acquisitions at high frame rates, posing high demands on the sampling and processing hardware. Here we develop an end-to-end image reconstruction approach based on deep learning that significantly reduces the amount of data necessary while retaining the imaging performance. We trained a convolutional neural network to learn the power Doppler reconstruction function from sparse sequences of ultrasound data with a compression factor up to 95%, using high-quality images from in vivo acquisitions in rats. We tested the imaging performance in a functional neuroimaging application. We demonstrate that time series of power Doppler images can be reconstructed with sufficient accuracy to detect the small changes in cerebral blood volume (~10%) characteristic of task-evoked cortical activation, even though the network was not formally trained to reconstruct such image series. The proposed platform may facilitate the development of this neuroimaging modality in any setting where dedicated hardware is not available or in clinical scanners.

bioengineering↗