title: Up-regulation of neurofilament light chains is associated with diminished immunoreactivities for MAP2 and tau after ischemic stroke in rodents and in a human case.
abstract: As stroke therapies are still limited to a minority of patients, efforts have been intensified to an improved understanding of pathophysiological processes during ischemia formation, potentially allowing the development of specific therapeutic interventions. In this context, cytoskeletal elements became evident as key players during the transition process towards long-lasting tissue damage. This study focused on ischemia-related alterations of the cytoskeleton with a special focus on microtubule-associated proteins and neurofilament light chains (NF-L). Immunohistochemical analyses were applied to brain sections of mice and rats after experimental stroke and to autoptic samples from a stroke patient. To consider translational aspects, a thromboembolic model of stroke in rats, closely mimicking the human situation, was used in addition to the filament-based model of focal cerebral ischemia in mice. One day after ischemia onset, immunoreactivity of microtubule-associated protein tau and microtubule-associated protein-2 (MAP2) was reduced in ischemic areas. These findings were consistently present in the ischemia-affected striatum and the neocortex. In a quite opposite fashion, ischemic areas displayed NF-L-immunoreactivity in neuropathologically altered fibers, local agglomerations probably related to degraded cell bodies and neocortical pyramidal cells. Notably, up-regulation of NF-L was also confirmed in infarcted tissue from a human brain sample. Furthermore, analyses of rodent brain tissue revealed corkscrew curl-like fibers as a special feature of MAP2 in the ischemia-affected hippocampus. In conclusion, this study provides evidence for an opposite reaction of microtubule-associated proteins and neurofilaments after focal cerebral ischemia. Accordingly, cytoskeletal elements appear as a promising target for stroke treatment.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 04103 Leipzig, Germany. Electronic address: hartig@medizin.uni-leipzig.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.affiliation: Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Krueger
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 04103 Leipzig, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hofmann
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 04103 Leipzig, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Preißler
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 04103 Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Märkel
authors.affiliation: Department for Neuropathology, University of Leipzig, Liebigstr. 26, 04103 Leipzig, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Frydrychowicz
authors.affiliation: Department for Neuropathology, University of Leipzig, Liebigstr. 26, 04103 Leipzig, Germany.
authors.forename: Wolf C
authors.initials: WC
authors.lastname: Mueller
authors.affiliation: Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Michalski
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism*; D015854:Up-Regulation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins
keywords: Cytoskeleton; Ischemic brain; Microtubule; Stroke; Tau; Triple fluorescence labeling