Melatonin attenuates reactive astrogliosis and glial scar formation following cerebral ischemia and reperfusion injury mediated by GSK-3β and RIP1K.
astrocytes
axonal regeneration
cerebral ischemia
glial scar
melatonin
neuroinflammation
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
26
10
2021
received:
30
06
2021
accepted:
15
11
2021
pubmed:
27
11
2021
medline:
6
5
2022
entrez:
26
11
2021
Statut:
ppublish
Résumé
Even though astrocytes have been widely reported to support several brain functions, studies have emerged that they exert deleterious effects on the brain after ischemia and reperfusion (I/R) injury. The present study investigated the neuroprotective effects of melatonin on the processes of reactive astrogliosis and glial scar formation, as well as axonal regeneration after transient middle cerebral artery occlusion. Male Wistar rats were randomly divided into four groups: sham-operated, I/R, I/R treated with melatonin, and I/R treated with edaravone. All drugs were administered via intraperitoneal injection at the onset of reperfusion and were continued until the rats were sacrificed on Day 7 or 14 after the surgery. Melatonin presented long-term benefits on cerebral damage after I/R injury, as demonstrated by a decreased infarct volume, histopathological changes, and reduced neuronal cell death. We also found that melatonin attenuated reactive astrogliosis and glial scar formation and, consequently, enhanced axonal regeneration and promoted neurobehavioral recovery. Furthermore, glycogen synthase kinase-3 beta (GSK-3β) and receptor-interacting serine/threonine-protein 1 kinase (RIP1K), which had previously been revealed as proteins involved in astrocyte responses, were significantly reduced after melatonin administration. Taken together, melatonin effectively counteracted the deleterious effects due to astrocyte responses and improved axonal regeneration to promote functional recovery during the chronic phase of cerebral I/R injury by inhibiting GSK-3β and RIP1K activities.
Substances chimiques
Neuroprotective Agents
0
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1818-1832Informations de copyright
© 2021 Wiley Periodicals LLC.
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