Tricellulin, α-Catenin and Microfibrillar-Associated Protein 5 Exhibit Concomitantly Altered Immunosignals along with Vascular, Extracellular and Cytoskeletal Elements after Experimental Focal Cerebral Ischemia

Int J Mol Sci. 2023 Jul 25;24(15):11893. doi: 10.3390/ijms241511893.

Abstract

Along with initiatives to understand the pathophysiology of stroke in detail and to identify neuroprotective targets, cell-stabilizing elements have gained increasing attention. Although cell culture experiments have indicated that tricellulin, α-catenin and microfibrillar-associated protein 5 (MFAP5) contribute to cellular integrity, these elements have not yet been investigated in the ischemic brain. Applying immunofluorescence labeling, this study explored tricellulin, MFAP5 and α-catenin in non-ischemic and ischemic brain areas of mice (24, 4 h of ischemia) and rats (4 h of ischemia), along with collagen IV and fibronectin as vascular and extracellular matrix constituents and microtubule-associated protein 2 (MAP2) and neurofilament light chain (NF-L) as cytoskeletal elements. Immunosignals of tricellulin and notably MFAP5 partially appeared in a fiber-like pattern, and α-catenin appeared more in a dotted pattern. Regional associations with vascular and extracellular constituents were found for tricellulin and α-catenin, particularly in ischemic areas. Due to ischemia, signals of tricellulin, MFAP5 and α-catenin decreased concomitantly with MAP2 and NF-L, whereby MFAP5 provided the most sensitive reaction. For the first time, this study demonstrated ischemia-related alterations in tricellulin, MFAP5 and α-catenin along with the vasculature, extracellular matrix and cytoskeleton. Confirmatory studies are needed, also exploring their role in cellular integrity and the potential for neuroprotective approaches in stroke.

Keywords: NVU; experimental stroke; focal cerebral ischemia; microfibrillar-associated protein 5; neurovascular unit; tricellulin; α-catenin.

MeSH terms

  • Animals
  • Brain Ischemia* / metabolism
  • Cerebral Infarction
  • Contractile Proteins
  • Cytoskeleton / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Ischemia
  • MARVEL Domain Containing 2 Protein
  • Mice
  • Rats
  • Stroke* / metabolism
  • alpha Catenin

Substances

  • alpha Catenin
  • MARVEL Domain Containing 2 Protein
  • Marveld2 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Contractile Proteins