The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients.
Atomic force microscopy
Biomarker
Cerebral ischemia
MAP2
NF-L
Stroke
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
05
01
2021
accepted:
22
03
2021
pubmed:
2
5
2021
medline:
28
12
2021
entrez:
1
5
2021
Statut:
ppublish
Résumé
In the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.
Identifiants
pubmed: 33931805
doi: 10.1007/s12035-021-02372-3
pii: 10.1007/s12035-021-02372-3
pmc: PMC8280005
doi:
Substances chimiques
Biomarkers
0
MAP2 protein, human
0
Microtubule-Associated Proteins
0
Neurofilament Proteins
0
neurofilament protein L
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4051-4069Subventions
Organisme : European Social Funds (ESF)
ID : 100270131
Organisme : European Research Council Advanced Grant
ID : 741350
Informations de copyright
© 2021. The Author(s).
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