Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells.

The zinc finger protein ZFYVE21 is involved in immune signaling. Using humanized mouse models, primary human cells, and patient samples, we identified a T cell-autonomous role for ZFYVE21 in promoting chronic vascular inflammation associated with allograft vasculopathy. Ischemia-reperfusion injury (IRI) stimulated endothelial cells to produce Hedgehog (Hh) ligands, which in turn induced the production of ZFYVE21 in a population of T memory cells with high amounts of the Hh receptor PTCH1 (PTCH cells, CD3CD4CD45ROPTCH1PD-1), vigorous recruitment to injured endothelia, and increased effector responses in vivo.

Pathologic characterization of canine multiple system degeneration in the Ibizan hound.

Canine multiple system degeneration (CMSD) is a progressive hereditary neurodegenerative disorder commonly characterized by neuronal degeneration and loss in the cerebellum, olivary nuclei, substantia nigra, and caudate nuclei. In this article, we describe 3 cases of CMSD in Ibizan hounds. All patients exhibited marked cerebellar ataxia and had cerebellar atrophy on magnetic resonance imaging.

Comparative Pathology of the Peripheral Nervous System.

The peripheral nervous system (PNS) relays messages between the central nervous system (brain and spinal cord) and the body. Despite this critical role and widespread distribution, the PNS is often overlooked when investigating disease in diagnostic and experimental pathology. This review highlights key features of neuroanatomy and physiology of the somatic and autonomic PNS, and appropriate PNS sampling and processing techniques.

Nerve Fiber Regeneration in Toxic Peripheral Neuropathy.

There is a striking difference in the potential for regeneration of injured axons in the central and peripheral nervous systems, which is important in neurotoxicologic studies. In contrast to the former, there is a ready mechanism for replacement of peripheral nerve axons that have degenerated following exposure to toxins, where long-distance axon regeneration and substantial functional recovery can occur. This relates at least in part to the nature of the glial and other supporting cells of the peripheral nerve.

Common Structural Lesions of the Peripheral Nervous System.

This review illustrates common lesions of peripheral nerve myelinated fibers that occur in toxic neuropathy. These distinctive structural changes help to define the site of toxicant activity and thus predict the course of neurotoxic disease and recovery. Neuronopathy is the condition where the primary injury is directed to the neuronal cell body giving rise to a peripheral nerve axon.