BRIEF RESEARCH REPORT article

Front. Neurosci.

Sec. Translational Neuroscience

Volume 19 - 2025 | doi: 10.3389/fnins.2025.1593948

This article is part of the Research TopicRecent Advances in Translational Neurovascular and Cerebroprotection ResearchView all 4 articles

Local arrangement of microfibrillar-associated protein 5 with components of the neurovascular unit, extracellular matrix, and cytoskeleton in non-and ischemia-affected brain regions of mice

Provisionally accepted
  • Leipzig University, Leipzig, Germany

The final, formatted version of the article will be published soon.

Stroke often leads to death or functional impairment, while neuroprotective strategies are still lacking. Among the mechanisms contributing to long-lasting tissue damage and yielding thus interest for therapeutic targets, an affection of cytoskeletal elements has been considered. Following the first detection of the microfibrillar-associated protein 5 (MFAP5) in the brain, this study aimed to explore its local arrangement with components of the neurovascular unit (NVU), extracellular matrix (ECM), and cytoskeleton in non-and ischemia-affected neocortical regions of mice. Fluorescence labeling was used to visualize MFAP5 simultaneously with neurons, glial cells, vasculature, perineuronal nets and fibronectin as part of the ECM, and neurofilament light chain (NF-L) and microtubule-associated protein 2 (MAP2) as representatives of the cytoskeleton. Fluorescence-based microscopy, confocal laser scanning microscopy, and 3D surface reconstruction served for analyses. MFAP5 was detected in a predominantly fiber-like and partially surrounding formation associated with neuronal processes and cell bodies. In the ischemia-affected region, MFAP5 markedly diminished, but a few fiber-like structures were maintained with a thinned, partially fragmented, and twisted aspect. MFAP5 exhibited no clear regional association with microglia, astroglia, or parts of the vasculature and ECM. However, the local arrangement of MFAP5 and its change due to focal cerebral ischemia was comparable to that of NF-L and MAP2. This study provided a comprehensive description of MFAP5 after experimental stroke and identified similarities with MAP2 and NF-L. Thus, MFAP5 might represent a component of the neuronal cytoskeleton and is of interest for further research regarding pathophysiological processes and the potential for neuroprotective approaches.

Keywords: Stroke, focal cerebral ischemia, neurovascular unit, NVU, Microfibrillar-associated protein 5, MFAP5, NF-L, MAP2

Received: 14 Mar 2025; Accepted: 12 May 2025.

Copyright: © 2025 Höfling, Rossner, Flachmeyer, Härtig and Michalski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dominik Michalski, Leipzig University, Leipzig, Germany

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