Astrocyte TrkB promotes brain injury and edema formation in ischemic stroke

Astrocyte TrkB promotes brain injury and edema formation in ischemic stroke

Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in...

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Bibliographic Details
Published in:Neurobiology of disease Vol. 201; p. 106670
Main Authors: Colombo, Emanuela, Bacigaluppi, Marco, Bartoccetti, Michela, Triolo, Daniela, Bassani, Claudia, Bergamaschi, Andrea, Descamps, Hélène C., Gullotta, Giorgia Serena, Henley, Maria, Piccoli, Marco, Anastasia, Luigi, Pitt, David, Newcombe, Jia, Martino, Gianvito, Farina, Cinthia
Format: Journal Article
Language:English
Published: United States Elsevier Inc 15-10-2024
Elsevier
Subjects:
AQP4
Astrocyte
Stroke
TrkB
MCAO
PBS
Stroke
BBB
GLT1
TBS
MRI
CNS
DAPI
AQP4
PFA
Astrocyte
GFAP
BSA
GLAST
TrkB
FBS
BrdU
2ME2
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Summary:Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in astrocytes after human and experimental stroke, and transgenic mice lacking astrocyte TrkB displayed significantly smaller lesion volume, lower brain atrophy and better motor performance than control animals after transient middle cerebral artery occlusion. Neuropathological studies evidenced that edema directly correlated with astrogliosis and was limited in transgenic mice. Importantly, adaptive levels of the water channel AQP4 was astrocyte TrkB-dependent as AQP4 upregulation after stroke did not occur in mice lacking astrocyte TrkB. In vitro experiments with wild-type and/or TrkB-deficient astrocytes highlighted TrkB-dependent upregulation of AQP4 via activation of HIF1-alpha under hypoxia. Collectively, our observations indicate that TrkB signaling in astrocytes contributes to the development of edema and worsens cerebral ischemia. •Astrocyte TrkB is upregulated in human and experimental brain ischemia.•Mice lacking astrocyte TrkB display reduced lesion volume and edema after stroke.•Astrocyte TrkB supports hypoxia-induced AQP4 levels via HIF-1α.
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ISSN:0969-9961
1095-953X
1095-953X
DOI:10.1016/j.nbd.2024.106670