Inflammatory response and white matter damage after microinjections of endothelin-1 into the rat striatum

• Published in: Brain research Vol. 1200; pp. 78 - 88
• Main Authors: Souza-Rodrigues, R.D, Costa, A.M.R, Lima, R.R, Dos Santos, C.D, Picanço-Diniz, C.W, Gomes-Leal, W
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 20-03-2008; Amsterdam Elsevier; New York, NY
• Subjects: Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - metabolism; Animals; Axonal damage; Axons - drug effects; Axons - metabolism; Axons - pathology; Biological and medical sciences; Biomarkers - analysis; Biomarkers - metabolism; Brain Ischemia - chemically induced; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cerebral Arteries - drug effects; Cerebral Arteries - metabolism; Cerebral Arteries - physiopathology; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - physiology; Corpus Striatum - drug effects; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Demyelinating Diseases - chemically induced; Demyelinating Diseases - pathology; Demyelinating Diseases - physiopathology; Disease Progression; Encephalitis - chemically induced; Encephalitis - pathology; Encephalitis - physiopathology; Endothelin-1 - toxicity; Focal ischemia; Macrophages; Male; Medical sciences; Microcirculation - drug effects; Microcirculation - metabolism; Microcirculation - physiopathology; Microglia - drug effects; Microglia - metabolism; Microinjections; Myelin; Myelin Basic Protein - analysis; Myelin Basic Protein - metabolism; Nerve Fibers, Myelinated - drug effects; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - pathology; Neurology; Neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; Rats; Rats, Wistar; Vascular diseases and vascular malformations of the nervous system; Focal ischemia; Axonal damage; Macrophages; Myelin; Neutrophils; Nervous system diseases; Rat; Rodentia; Central nervous system; Cardiovascular disease; Basal ganglion; Corpus striatum; Endothelin 1; Inflammation; White matter; Encephalon; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Focal ischemia,Neutrophils,Macrophages,Myelin,Axonal damage; Animal; Central nervous system disease; Brain ischemia; Neutrophil; Cerebrovascular disease; Macrophage
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.11.025

Abstract Following acute and chronic neurodegenerative disorders, a cascade of pathological events including inflammatory response, excitotoxicity and oxidative stress induces secondary tissue loss in both gray and white matter. Axonal damage and demyelination are important components of the white matter demise during these diseases. In spite of this, a few studies have addressed the patterns of inflammatory response, axonal damage and demyelination following focal ischemic damage to the central nervous system (CNS). In the present study, we describe the patterns of inflammatory response, axonal damage and myelin impairment following microinjections of 10 pmol of endothelin-1 into the rat striatum. Animals were perfused at 1 day, 3 days and 7 days after injection. 20 μm sections were stained by hematoxylin and immunolabeled for neutrophils (anti-MBS-1), activated macrophages/microglia (anti-ED1), damaged axons (anti-βAPP) and myelin (anti-MBP). The evolution of acute inflammation was quantitatively assessed by cell counts in different survival times. There was recruitment of both neutrophils and macrophages to the damaged striatal parenchyma with maximum recruitment at 1 day and 7 days, respectively. Progressive myelin impairment in the striatal white matter tracts has been observed mainly at later survival times. β-APP+ endbulbs were not present in all evaluated time points. These results suggest that progress myelin impairment in the absence of damage to axonal cylinder is a feature of white matter pathology following endothelin-1-induced focal striatal ischemia.