Comparative analysis of chronic neuropathic pain and pain assessment in companion animals and humans.

Chronic neuropathic pain is underdiagnosed in companion animals. This paper will review the definition of pain and how classification and grading of neuropathic pain can be applied from human to veterinary medicine to increase the recognition of and the confidence in a neuropathic pain diagnosis. The mechanisms of nociception and the pathophysiology of the sensory systems that underlie the transition to chronic pain are described.

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.

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 Dearth of Representation in FDA Approved Drug Trials.

The generalizability of data derived from randomized controlled trials is of paramount importance given their utility in the Food & Drug Administration (FDA) drug approval process. An essential part of this process is the inclusion of reliably reported gender, race and ethnicity data in trials that lead to FDA drug approval. Despite previous mandates by the FDA and Clinicaltrials.

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.

Case Report: MRI, Clinical, and Pathological Correlates of Bromethalin Toxicosis in Three Dogs.

Bromethalin toxicosis is an increasingly common clinical presentation in dogs that may be fatal depending on the extent of intoxication. Antemortem diagnosis of bromethalin toxicosis was achieved in three dogs by demonstration of the active metabolite desmethylbromethalin in fat or serum. Magnetic resonance imaging (MRI) findings were consistent with a diffuse leukoencephalopathy with restricted diffusion and prominent involvement of the corticospinal motor tracts on T2-weighted and diffusion-weighted sequences.

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.

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.

Deletion of lynx1 reduces the function of α6* nicotinic receptors.

The α6 nicotinic acetylcholine receptor (nAChR) subunit is an attractive drug target for treating nicotine addiction because it is present at limited sites in the brain including the reward pathway. Lynx1 modulates several nAChR subtypes; lynx1-nAChR interaction sites could possibly provide drug targets. We found that dopaminergic cells from the substantia nigra pars compacta (SNc) express lynx1 mRNA transcripts and, as assessed by co-immunoprecipitation, α6 receptors form stable complexes with lynx1 protein, although co-transfection with lynx1 did not affect nicotine-induced currents from cell lines transfected with α6 and β2.

Optically transparent multi-suction electrode arrays.

Multielectrode arrays (MEAs) allow for acquisition of multisite electrophysiological activity with submillisecond temporal resolution from neural preparations. The signal to noise ratio from such arrays has recently been improved by substrate perforations that allow negative pressure to be applied to the tissue; however, such arrays are not optically transparent, limiting their potential to be combined with optical-based technologies. We present here multi-suction electrode arrays (MSEAs) in quartz that yield a substantial increase in the detected number of units and in signal to noise ratio from mouse cortico-hippocampal slices and mouse retina explants.

Lynx1 shifts α4β2 nicotinic receptor subunit stoichiometry by affecting assembly in the endoplasmic reticulum.

Glycosylphosphatidylinositol-anchored neurotoxin-like receptor binding proteins, such as lynx modulators, are topologically positioned to exert pharmacological effects by binding to the extracellular portion of nAChRs. These actions are generally thought to proceed when both lynx and the nAChRs are on the plasma membrane. Here, we demonstrate that lynx1 also exerts effects on α4β2 nAChRs within the endoplasmic reticulum.

Lynx1 supports neuronal health in the mouse dorsal striatum during aging: an ultrastructural investigation.

Nicotinic acetylcholine receptors have been shown to participate in neuroprotection in the aging brain. Lynx protein modulators dampen the activity of the cholinergic system through direct interaction with nicotinic receptors. Although lynx1 null mutant mice exhibit augmented learning and plasticity, they also exhibit macroscopic vacuolation in the dorsal striatum as they age, detectable at the optical microscope level.

SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis.

Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5.

Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network.

Hereditary spastic paraplegias (HSPs; SPG1-45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology.