Pathology and Pathogenesis of Brain Lesions Produced by Clostridium Perfringens Type D Epsilon Toxin.

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dc.contributor.authorFinnie, J.W.
dc.contributor.authorUzal, F.A.
dc.date.issued2022
dc.description.abstractClostridium perfringens type D epsilon toxin (ETX) produces severe, and frequently fatal, neurologic disease in ruminant livestock. The disorder is of worldwide distribution and, although vaccination has reduced its prevalence, ETX still causes substantial economic loss in livestock enterprises. The toxin is produced in the intestine as a relatively inactive prototoxin, which is subsequently fully enzymatically activated to ETX. When changed conditions in the intestinal milieu, particularly starch overload, favor rapid proliferation of this clostridial bacterium, large amounts of ETX can be elaborated. When sufficient toxin is absorbed from the intestine into the systemic circulation and reaches the brain, two neurologic syndromes can develop from this enterotoxemia. If the brain is exposed to large amounts of ETX, the lesions are fundamentally vasculocentric. The neurotoxin binds to microvascular endothelial receptors and other brain cells, the resulting damage causing increased vascular permeability and extravasation of plasma protein and abundant fluid into the brain parenchyma. While plasma protein, particularly albumin, pools largely perivascularly, the vasogenic edema becomes widely distributed in the brain, leading to a marked rise in intracranial pressure, coma, sometimes cerebellar herniation, and, eventually, often death. When smaller quantities of ETX are absorbed into the bloodstream, or livestock are partially immune, a more protracted clinical course ensues. The resulting brain injury is characterized by bilaterally symmetrical necrotic foci in certain selectively vulnerable neuroanatomic sites, termed focal symmetrical encephalomalacia. ETX has also been internationally listed as a potential bioterrorism agent. Although there are no confirmed human cases of ETX intoxication, the relatively wide species susceptibility to this toxin and its high toxicity mean it is likely that human populations would also be vulnerable to its neurotoxic actions. While the pathogenesis of ETX toxicity in the brain is incompletely understood, the putative mechanisms involved in neural lesion development are discussed.
dc.description.statementofresponsibilityJohn W. Finnie, Francisco A. Uzal
dc.identifier.citationInternational Journal of Molecular Sciences, 2022; 23(16):9050-1-9050-17
dc.identifier.doi10.3390/ijms23169050
dc.identifier.issn1422-0067
dc.identifier.issn1422-0067
dc.identifier.orcidFinnie, J.W. [0000-0003-2277-1693]
dc.identifier.urihttps://hdl.handle.net/2440/146051
dc.language.isoen
dc.publisherMDPI AG
dc.rights© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.source.urihttps://doi.org/10.3390/ijms23169050
dc.subjectClostridium perfringens type D; epsilon toxin; neuropathology; pathogenesis
dc.subject.meshBrain
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshClostridium perfringens
dc.subject.meshEnterotoxemia
dc.subject.meshNecrosis
dc.subject.meshIntracranial Pressure
dc.titlePathology and Pathogenesis of Brain Lesions Produced by Clostridium Perfringens Type D Epsilon Toxin.
dc.typeJournal article
pubs.publication-statusPublished

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