Language:

Malignant astrocyte swelling and impaired glutamate clearance drive the expansion of injurious spreading depolarization foci

Journal of cerebral blood flow and metabolism, 2022-04, Vol.42 (4), p.584-599 [Peer Reviewed Journal]

The Author(s) 2021 ;Distributed under a Creative Commons Attribution 4.0 International License ;The Author(s) 2021 2021 International Society for Cerebral Blood Flow and Metabolism ;ISSN: 0271-678X ;EISSN: 1559-7016 ;DOI: 10.1177/0271678X211040056 ;PMID: 34427145

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Malignant astrocyte swelling and impaired glutamate clearance drive the expansion of injurious spreading depolarization foci
Author: Menyhárt, Ákos ; Frank, Rita ; Farkas, Attila E ; Süle, Zoltán ; Varga, Viktória É ; Nyúl-Tóth, Ádám ; Meiller, Anne ; Ivánkovits-Kiss, Orsolya ; Lemale, Coline L ; Szabó, Írisz ; Tóth, Réka ; Zölei-Szénási, Dániel ; Woitzik, Johannes ; Marinesco, Stephane ; Krizbai, István A ; Bari, Ferenc ; Dreier, Jens P ; Farkas, Eszter
Subjects: Animals ; Astrocytes - metabolism ; Brain Edema - pathology ; Brain Injuries - metabolism ; Edema - metabolism ; Glutamic Acid - metabolism ; Life Sciences ; Original ; Rats ; Sodium-Potassium-Chloride Symporters - metabolism
Is Part Of: Journal of cerebral blood flow and metabolism, 2022-04, Vol.42 (4), p.584-599
Description: Spreading depolarizations (SDs) indicate injury progression and predict worse clinical outcome in acute brain injury. We demonstrate in rodents that acute brain swelling upon cerebral ischemia impairs astroglial glutamate clearance and increases the tissue area invaded by SD. The cytotoxic extracellular glutamate accumulation (>15 µM) predisposes an extensive bulk of tissue (4–5 mm2) for a yet undescribed simultaneous depolarization (SiD). We confirm in rat brain slices exposed to osmotic stress that SiD is the pathological expansion of prior punctual SD foci (0.5–1 mm2), is associated with astrocyte swelling, and triggers oncotic neuron death. The blockade of astrocytic aquaporin-4 channels and Na+/K+/Cl− co-transporters, or volume-regulated anion channels mitigated slice edema, extracellular glutamate accumulation (<10 µM) and SiD occurrence. Reversal of slice swelling by hyperosmotic mannitol counteracted glutamate accumulation and prevented SiD. In contrast, inhibition of glial metabolism or inhibition of astrocyte glutamate transporters reproduced the SiD phenotype. Finally, we show in the rodent water intoxication model of cytotoxic edema that astrocyte swelling and altered astrocyte calcium waves are central in the evolution of SiD. We discuss our results in the light of evidence for SiD in the human cortex. Our results emphasize the need of preventive osmotherapy in acute brain injury.
Publisher: London, England: SAGE Publications
Language: English
Identifier: ISSN: 0271-678X
EISSN: 1559-7016
DOI: 10.1177/0271678X211040056
PMID: 34427145
Source: SAGE Open Access Journals
GFMER Free Medical Journals
MEDLINE
PubMed Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Malignant astrocyte swelling and impaired glutamate clearance drive the expansion of injurious spreading depolarization foci

The Author(s) 2021 ;Distributed under a Creative Commons Attribution 4.0 International License ;The Author(s) 2021 2021 International Society for Cerebral Blood Flow and Metabolism ;ISSN: 0271-678X ;EISSN: 1559-7016 ;DOI: 10.1177/0271678X211040056 ;PMID: 34427145

Searching Remote Databases, Please Wait