Effect of leuprolide acetate, a GnRH agonist, on neuroinflammation and anxiety-like behavior after mild hypoxic-ischemic encephalopathy in rat model.
Journal
Neuroimmunomodulation
ISSN: 1423-0216
Titre abrégé: Neuroimmunomodulation
Pays: Switzerland
ID NLM: 9422763
Informations de publication
Date de publication:
22 Aug 2023
22 Aug 2023
Historique:
received:
12
05
2023
accepted:
31
07
2023
medline:
23
8
2023
pubmed:
23
8
2023
entrez:
22
8
2023
Statut:
aheadofprint
Résumé
Mild hypoxic-ischemic encephalopathy (HIE) is a condition that predisposes to negative outcomes such as neuroanatomical injury, mood disorders, and motor or cognitive disabilities. The neuroinflammation plays an important role in the neurological damage, therefore reducing it could provide neuroprotection. The leuprolide acetate (LA) has shown to have neuroregenerative and immunomodulator properties in other nervous system injuries. The aim of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor activity and behavior in a subacute phase. Forty-five Wistar rats on postnatal day 7 were divided into Sham, HIE treated with saline solution (HIE-SS) and HIE-LA. The HIE was performed cutting of the right carotid artery followed by 60 min of hypoxia. The expression of the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and the chemokine CXCL-1 were evaluated 72 h after HIE by RT-qPCR and the motor activity and behavior were evaluated by open field test at postnatal day 33. HIE-SS animals showed increased expression of IL-1β, TNF-α, IFN-γ and CXCL-1 genes in injured tissue. However, the HIE-LA group exhibited similar expression levels of IL-1β and TNF-α to the Sham group, while IFN-γ and CXCL-1 mRNA expression were attenuated with LA treatment. LA treatment also prevented anxiety-like behavior in the open field test. Treatment with LA partially reverses HIE-induced neuroinflammation and prevents anxiety-like behavior in neonatal rats.
Sections du résumé
BACKGROUND
BACKGROUND
Mild hypoxic-ischemic encephalopathy (HIE) is a condition that predisposes to negative outcomes such as neuroanatomical injury, mood disorders, and motor or cognitive disabilities. The neuroinflammation plays an important role in the neurological damage, therefore reducing it could provide neuroprotection. The leuprolide acetate (LA) has shown to have neuroregenerative and immunomodulator properties in other nervous system injuries.
OBJECTIVE
OBJECTIVE
The aim of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor activity and behavior in a subacute phase.
METHOD
METHODS
Forty-five Wistar rats on postnatal day 7 were divided into Sham, HIE treated with saline solution (HIE-SS) and HIE-LA. The HIE was performed cutting of the right carotid artery followed by 60 min of hypoxia. The expression of the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and the chemokine CXCL-1 were evaluated 72 h after HIE by RT-qPCR and the motor activity and behavior were evaluated by open field test at postnatal day 33.
RESULTS
RESULTS
HIE-SS animals showed increased expression of IL-1β, TNF-α, IFN-γ and CXCL-1 genes in injured tissue. However, the HIE-LA group exhibited similar expression levels of IL-1β and TNF-α to the Sham group, while IFN-γ and CXCL-1 mRNA expression were attenuated with LA treatment. LA treatment also prevented anxiety-like behavior in the open field test.
CONCLUSION
CONCLUSIONS
Treatment with LA partially reverses HIE-induced neuroinflammation and prevents anxiety-like behavior in neonatal rats.
Identifiants
pubmed: 37607495
pii: 000533388
doi: 10.1159/000533388
pmc: PMC10614564
doi:
Types de publication
News
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
The Author(s). Published by S. Karger AG, Basel.
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