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 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.
Authors
- Claudia Bassani
- Luigi Anastasia (ORCID: https://orcid.org/0000-0002-0712-2161)
- David Pitt (ORCID: https://orcid.org/0000-0002-6407-9542)
- Gianvito Martino (ORCID: https://orcid.org/0000-0003-1295-9131)
- Daniela Triolo
- Hélène C. Descamps (ORCID: https://orcid.org/0000-0001-5591-5839)
- Marco Bacigaluppi
- Giorgia Serena Gullotta (ORCID: https://orcid.org/0000-0002-9580-6765)
- Marco Piccoli (ORCID: https://orcid.org/0000-0002-9461-2715)
- Jia Newcombe (ORCID: https://orcid.org/0000-0001-9609-7975)
- Cinthia Farina (ORCID: https://orcid.org/0000-0002-4466-9676)
- Andrea Bergamaschi (ORCID: https://orcid.org/0000-0001-9010-2577)
- Emanuela Colombo (ORCID: https://orcid.org/0000-0001-8754-1739)
- Maria Henley
- Michela Bartoccetti
Institutions
- Vita-Salute San Raffaele University (IT)
- Yale University (US)
- IRCCS Policlinico San Donato (IT)
- National Hospital for Neurology and Neurosurgery (GB)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
- University College London (GB)
Publication Details
- Journal
- Neurobiology of Disease
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1016/j.nbd.2024.106670
- Citations
- 5
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.24
Funders
- Ministero della Salute