Tumor-derived extracellular vesicles disrupt the blood-brain barrier endothelium following high-frequency irreversible electroporation.

High-frequency irreversible electroporation (H-FIRE), a nonthermal brain tumor ablation therapeutic, generates a central tumor ablation zone while transiently disrupting the peritumoral blood-brain barrier (BBB). We hypothesized that bystander effects of H-FIRE tumor cell ablation, mediated by small tumor-derived extracellular vesicles (sTDEV), disrupt the BBB endothelium. Monolayers of bEnd.

A prospective evaluation of succinct prednisone tapering after brain tumor irradiation in dogs.

Background: To ameliorate anticipated or ongoing neurological deficits, dogs undergoing brain tumor irradiation often are prescribed lengthy courses of prednisone PO during and after radiotherapy (RT). This practice can contribute to unwanted corticosteroid-associated morbidity and may be unnecessary.

Objective: Determine whether long-term corticosteroid dependency can be minimized by use of succinct prednisone tapering.

Burst sine wave electroporation (B-SWE) for expansive blood-brain barrier disruption and controlled non-thermal tissue ablation for neurological disease.

The blood-brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier. This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE). Using an rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared.

Ultrasound-Guided Mechanical High-Intensity Focused Ultrasound (Histotripsy) Through an Acoustically Permeable Polyolefin-Based Cranioplasty Device.

Unlabelled: Histotripsy is a non-thermal focused ultrasound therapy in development for the non-invasive ablation of cancerous tumors. Intracranial histotripsy has been limited by significant pressure attenuation through the skull, requiring large, complex array transducers to overcome this effect.

Objective: Recently, a biocompatible, polyolefin-based cranioplasty device was developed to allow ultrasound (US) transmission into the intracranial space with minimal distortion.

An Illustrated Scoping Review of the Magnetic Resonance Imaging Characteristics of Canine and Feline Brain Tumors.

Magnetic resonance imaging (MRI) is used pervasively in veterinary practice for the antemortem diagnosis of intracranial tumors. Here, we provide an illustrated summary of the published MRI features of primary and secondary intracranial tumors of dogs and cats, following PRISMA scoping review guidelines. The PubMed and Web of Science databases were searched for relevant records, and input from stakeholders was solicited to select data for extraction.

Evaluation of neurofilament light chain as a biomarker in dogs with structural and idiopathic epilepsy.

Background: Neurofilament light chain (NfL) is a frequently used biomarker in humans for both diagnostic and therapeutic monitoring purposes in various neurologic diseases.

Hypothesis/objectives: It was hypothesized that dogs with diagnosed structural epilepsy (SE) would have a significantly higher serum NfL concentrations compared to dogs with idiopathic epilepsy (IE). The secondary hypothesis was that dogs would have a significantly higher serum NfL concentrations when measured within 7 days after a seizure compared to being seizure-free for at least 30 days.

Randomized Controlled Trial of Durotomy as an Adjunct to Routine Decompressive Surgery for Dogs With Severe Acute Spinal Cord Injury.

Although many interventions for acute spinal cord injury (SCI) appear promising in experimental models, translation directly from experimental animals to human patients is a large step that can be problematic. Acute SCI occurs frequently in companion dogs and may provide a model to ease translation. Recently, incision of the dura has been highlighted in both research animals and human patients as a means of reducing intraspinal pressure, with a view to improving perfusion of the injured tissue and enhancing functional recovery.

Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumors.

Neurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood-brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment.

Magnetic resonance and computed tomographic imaging characteristics and potential molecular mechanisms of feline meningioma associated calvarial hyperostosis.

Meningiomas are the most common feline primary brain tumours, and calvarial hyperostosis (CH) is frequently documented in association with this neoplastic entity. The clinical significance of and mechanisms driving the formation of CH in cats with meningiomas are poorly understood, although tumour invasion into the skull and tumour production of cytokines and enzymes have been implicated as causes of CH in humans. This retrospective study investigated relationships between signalment, MRI or CT imaging features, histopathologic tumour characteristics, alkaline phosphatase (ALP) isoenzyme concentrations, tumour expression of matrix metalloproteinases (MMP)-2, MMP-9, and interleukin-6 (IL-6), and progression free survival times (PFS) following surgical treatment in 27 cats with meningiomas with (n = 15) or without (n = 12) evidence of CH.

The T2-FLAIR mismatch sign as an imaging biomarker for oligodendrogliomas in dogs.

Background: In humans, the T2-weighted (T2W)-fluid-attenuated inversion recovery (FLAIR) mismatch sign (T2FMM) is a specific imaging biomarker for the isocitrate dehydrogenase 1 (IDH1)-mutated, 1p/19q non-codeleted low-grade astrocytomas (LGA). The T2FMM is characterized by a homogeneous hyperintense T2W signal and a hypointense signal with a hyperintense peripheral rim on FLAIR sequences. In gliomas in dogs, the T2FMM has not been described.

High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas.

Background: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas.

Methods: Hydrogel tissue scaffolds and numerical modeling were used to inform H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model.

Solid Fiber Inside of Capillary and Modified Fusion-Spliced Fiber Optic Microneedle Devices for Improved Light Transmission Efficiency.

Convection-enhanced delivery (CED) is a drug delivery technique used to deliver therapeutics directly to the brain and is a continually evolving technique to treat glioblastoma. Early versions of CED have proven to result in inadequate drug volume dispersed (V), increasing the likelihood of tumor recurrence. Fiber optic microneedle devices (FMDs) with the ability to deliver fluid and thermal energy simultaneously have shown an ability to increase V, but FMDs have historically had low light transmission efficiency.

Advancements in drug delivery methods for the treatment of brain disease.

The blood-brain barrier (BBB) presents a formidable obstacle to the effective delivery of systemically administered pharmacological agents to the brain, with ~5% of candidate drugs capable of effectively penetrating the BBB. A variety of biomaterials and therapeutic delivery devices have recently been developed that facilitate drug delivery to the brain. These technologies have addressed many of the limitations imposed by the BBB by: (1) designing or modifying the physiochemical properties of therapeutic compounds to allow for transport across the BBB; (2) bypassing the BBB by administration of drugs alternative routes; and (3) transiently disrupting the BBB (BBBD) using biophysical therapies.

High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood-Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation.

Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood-brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms.

Constant Pressure Convection-Enhanced Delivery Increases Volume Dispersed With Catheter Movement in Agarose.

Convection-enhanced delivery (CED) has been extensively studied for drug delivery to the brain due to its inherent ability to bypass the blood-brain barrier. Unfortunately, CED has also been shown to inadequately distribute therapeutic agents over a large enough targeted tissue volume to be clinically beneficial. In this study, we explore the use of constant pressure infusions in addition to controlled catheter movement as a means to increase volume dispersed (Vd) in an agarose gel brain tissue phantom.

Clinical, Diagnostic, and Imaging Findings in Three Juvenile Dogs With Paraspinal Hyperesthesia or Myelopathy as a Consequence of Hemophilia A: A Case Report.

Three juvenile dogs presented with an acute onset of paraspinal hyperesthesia and/or neurologic deficits. These dogs underwent anesthesia for MRI and additional diagnostics. The thoracolumbar MRI in Dog 1 revealed an accumulation of T2-weighted (T2W) hyperintense, T1-weighted (T1W) iso- to hyperintense, contrast enhancing extradural material.

Comparison of linear and volumetric criteria for the determination of therapeutic response in dogs with intracranial gliomas.

Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques.

Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method.

Incidence, risk factors, and outcomes for early postoperative seizures in dogs with rostrotentorial brain tumors after intracranial surgery.

Background: Seizures in the early postoperative period after intracranial surgery may affect outcome in dogs.

Objectives: To determine the incidence of early postoperative seizures (EPS) in dogs with brain tumors, identify specific risk factors for EPS, and determine if EPS affects outcome.

Animals: Eighty-eight dogs that underwent 125 intracranial surgeries for diagnosis and treatment of rostrotentorial brain tumors.

Biocompatibility of the fiberoptic microneedle device chronically implanted in the rat brain.

The fiberoptic microneedle device (FMD) is a fused-silica microcatheter capable of co-delivery of fluids and light that has been developed for convection-enhanced delivery and photothermal treatments of glioblastoma. Here we investigate the biocompatibility of FMD fragments chronically implanted in the rat brain in the context of evaluating potential mechanical device failure. Fischer rats underwent craniectomy procedures for sham control (n = 16) or FMD implantation (n = 16) within the brain.

An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields.

The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing.

Primary orthostatic tremor and orthostatic tremor-plus in dogs: 60 cases (2003-2020).

Background: Orthostatic tremor (OT) is a rare movement disorder characterized by high-frequency (>12 Hz) involuntary, rhythmic, sinusoidal movements affecting predominantly the limbs while standing.

Objective: To describe the signalment, presenting complaints, phenotype, diagnostic findings, treatment, and outcome of a large sample of dogs with OT.

Animals: Sixty dogs diagnosed with OT based on conscious electromyography.

High-frequency irreversible electroporation brain tumor ablation: exploring the dynamics of cell death and recovery.

Improved therapeutics for malignant brain tumors are urgently needed. High-frequency irreversible electroporation (H-FIRE) is a minimally invasive, nonthermal tissue ablation technique, which utilizes high-frequency, bipolar electric pulses to precisely kill tumor cells. The mechanisms of H-FIRE-induced tumor cell death and potential for cellular recovery are incompletely characterized.