Biology subjects

Dobos, A. B.

Publications and source records attributed to Dobos, A. B..

5 recordsLinked to original sources

bioRxiv2026

Modular chronic cranial platform for longitudinal functional ultrasound, optical, and ECoG recording in a gyrencephalic model species

Understanding cortical function in large, gyrencephalic brains requires following the same tissue over time and interrogating it through complementary methods - yet in practice each recording modality is run on its own preparation, across separate animals and sessions that cannot be quantitatively related, while the recorded cortex can rarely be revisited. Functional ultrasound (fUS), widefield optical imaging, and electrocorticography (ECoG) are individually mature and strongly complementary, but no single preparation has combined all three within the same chronically accessible tissue in a gyrencephalic brain. Here we present a modular chronic cranial platform, validated in three cats with implants remaining functional for up to 3.3 years that unites these modalities in one customized chamber built around fUS as an anchor modality. The platform also supports fUS imaging in awake, head-unrestrained animals, with activation maps remaining spatially consistent across imaging days. By providing stable, quantitatively reproducible access to the same cortical region over time, this platform enables longitudinal, multimodal characterization of cortical function within individual subjects.

neuroscience↗

bioRxiv2026

Pharmacokinetically optimized anesthesia enables long-term functional ultrasound imaging in the cat visual cortex

Functional ultrasound imaging (fUSI) measures cerebral blood-volume responses, so anesthesia protocols developed for BOLD fMRI may not preserve its signal. We screened three fMRI-derived anesthesia regimens for visually evoked fUSI in the cat visual cortex. Isoflurane-ketamine-medetomidine produced the strongest and most consistent responses, but the standard intramuscular medetomidine bolus suppressed the signal in one sensitive cat. Pharmacokinetic modeling guided replacement of this bolus with controlled intravenous dosing, restoring the visual response while maintaining physiological stability. The same weight-based regimen produced robust responses in the other animals. In a direct within-session test, response strength was equivalent in recordings separated by more than three hours. Across 464 recordings from 51 sessions in three cats, it showed no temporal drift during follow-up extending to 23 months. Visually evoked activation also remained clear relative to a small awake dataset, although equivalence was not established. PK-guided control of medetomidine exposure therefore enables stable, repeated fUSI of the cat visual cortex over hours to years.

neuroscience↗

bioRxiv2026

Prevention of mRNA vaccine-induced anaphylaxis by peripheral cyclooxygenase inhibitors in an anti-PEG hyperimmune pig model: clinical relevance for nanomedicine-induced infusion reactions

Anti-polyethylene glycol (PEG) hyperimmune pigs, immunized against PEG, provide a sensitive experimental model for the rare anaphylactic reactions induced by mRNA-PEGylated lipid nanoparticle (LNP)-based COVID-19 vaccines, such as Comirnaty. These pseudo-allergic infusion reactions can usually be prevented or attenuated by multicomponent anti-inflammatory premedication regimens; however, no established protocol exists for mRNA-LNP-based COVID-19 vaccines. The aim of the present study was to identify an effective premedication strategy capable of preventing or attenuating these reactions in hypersensitive subjects, using the hyperimmune porcine model. We compared the protective effects of individual pretreatment components; dexamethasone, famotidine, levocetirizine, acetaminophen, diclofenac, indomethacin, by analyzing hemodynamic endpoints (systemic and pulmonary arterial pressure, pulse pressure). All tested compounds modulated Comirnaty-induced anaphylactic responses; however, only cyclooxygenase (COX) inhibitors provided complete protection against anaphylaxis and other abnormal processes. This finding is consistent with the low incidence of infusion reactions to cancer nanomedicines at the Shaare Zedek Oncology Center in Israel which uses COX-inhibitors as premedication. Given that most currently used human infusion-reaction prevention protocols do not include COX inhibitors, and that steroid-containing regimens may potentially counteract vaccine efficacy, our results suggest that COX inhibitors may offer a clinically effective standalone option or form the basis of simplified premedication regimens for preventing this life-threatening condition.

immunology↗

bioRxiv2026

Hemoperfusion of pigs with a carbon-cellulose cartridge: a pilot study revealing a new animal model of extended anaphylactic shock

To investigate the immune mechanisms underlying extracorporeal circulation-associated anaphylactoid reactions, we inserted externally perfused cartridges into the venous circulation of pigs, including a cellulose-coated activated-charcoal adsorbent (Adsorba(R) 300C), a polysulfone hollow-fiber membrane hemofilter, and polypropylene hollow-fiber-based heart-lung machine gas-exchange oxygenators. Blood was circulated using a roller pump, and the animals were monitored for systemic and pulmonary arterial pressures (SAP, PAP) changes, blood levels of complement C3a, thromboxane B2, and hemoglobin, blood cell counts and hematocrit. None of the cartridges caused major changes in these endpoints except the Adsorba(R) 300C, which displayed a fulminant anaphylactoid reaction characterized by profound hypotension, maximal pulmonary hypertension, hemoconcentration, thrombocytopenia and a surge of C3a and thromboxane B2, i.e., hallmarks of complement activation-related pseudoallergy. Within 15 min, the reaction advanced to profound hemodynamic collapse, which was managed with norepinephrine and cardiopulmonary resuscitation. After brief rebound hypertension, shock recurred despite repeated rounds of resuscitation until death. Considering that major adverse reactions with overlapping symptoms have been reported in humans subjected to hemoperfusion with the same cartridge, this porcine model provides clinically relevant insights into the mechanisms of extracorporeal circulation-induced anaphylactoid responses. Furthermore, the Adsorba(R) 300C-induced physiological changes along the immune-cardiopulmonary axis represents a new animal model for irreversible cardiovascular collapse escalating into shock.

immunology↗

bioRxiv2023

The COVID-19 mRNA vaccine Comirnaty induces anaphylactic shock in an anti-PEG hyperimmune large animal model: Role of complement in cardiovascular, hematological, and inflammatory mediator changes

BackgroundComirnaty, Pfizer-BioNTechs polyethylene-glycol (PEG)-containing Covid-19 vaccine, can cause hypersensitivity reactions (HSRs) in a small fraction of immunized people which can, very rarely, culminate in life-threatening anaphylaxis. A role of anti-PEG antibodies (Abs) has been proposed, but causality has not yet been proven in an animal model. This study aimed to provide such evidence using anti-PEG hyperimmune pigs (i.e., pigs displaying very high levels of anti-PEG Abs). We also sought to find evidence for the role of complement (C) activation and thromboxane A2 (TXA2) release in blood as contributing effects to anaphylaxis. MethodsPigs (n=6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v. the rise of anti-PEG IgG and IgM was measured in serial blood samples with ELISA. After 2-3 weeks, during the height of seroconversion, the animals were injected i.v. with 1/3 human vaccine dose (HVD) of Comirnaty, and the hemodynamic (PAP, SAP), cardiopulmonary (HR, EtCO2,), hematological parameters (WBC, granulocyte, lymphocyte, and platelet counts) and blood immune mediators (anti-PEG IgM and IgG Abs, C3a and TXA2) were measured as endpoints of HSRs. ResultsA week after immunization of 6 pigs with Doxebo, the level of anti-PEG IgM and IgG rose 5-10-thousands-fold in all animals, and they all developed anaphylactic shock to i.v. injection of 1/3 HVD of Comirnaty. The reaction, starting within 1 min, led to the abrupt decline of SAP along with maximal pulmonary hypertension, decreased pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and paralleling rises of plasma C3a and TXB2 levels. These vaccine effects were not observed in non-immunized pigs. ConclusionsConsistent with previous studies with PEGylated nano-liposomes, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty. The reaction involves C activation, and, hence, it represents C activation-related pseudo-allergy (CARPA). The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.

pharmacology and toxicology↗