Intranasal insulin attenuates hypoxia-ischemia-induced short-term sensorimotor behavioral disturbances, neuronal apoptosis, and brain damage in neonatal rats.

Autor:	Talati CP; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Lee JW; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Lu S; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.; Department of Neurology, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Ojeda NB; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Prakash V; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.; Department of Pathology, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Dankhara N; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Nielson TC; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Sandifer SP; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Bidwell GL 3rd; Department of Neurology, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Pang Y; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Fan LW; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Bhatt AJ; Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Jazyk:	angličtina
Zdroj:	Current research in neurobiology [Curr Res Neurobiol] 2023 Dec 27; Vol. 6, pp. 100123. Date of Electronic Publication: 2023 Dec 27 (Print Publication: 2024).
DOI:	10.1016/j.crneur.2023.100123
Abstrakt:	There is a significant need for additional therapy to improve outcomes for newborns with acute Hypoxic-ischemic (HI) encephalopathy (HIE). New evidence suggests that insulin could be neuroprotective. This study aimed to investigate whether intranasal insulin attenuates HI-induced brain damage and neurobehavioral dysfunction in neonatal rats. Postnatal day 10 (P10), Sprague-Dawley rat pups were randomly divided into Sham + Vehicle, Sham + Insulin, HI + Vehicle, and HI + Insulin groups with equal male-to-female ratios. Pups either had HI by permanent ligation of the right common carotid artery followed by 90 min of hypoxia (8% O2) or sham surgery followed by room air exposure. Immediately after HI or Sham, pups were given fluorescence-tagged insulin (Alex-546-insulin)/vehicle, human insulin (25 μg), or vehicle in each nare under anesthesia. Shortly after administration, widespread Alex-546-insulin-binding cells were detected in the brain, primarily co-localized with neuronal nuclei-positive neurons on double-immunostaining. In the hippocampus, phospho-Akt was activated in a subset of Alex-546-insulin double-labeled cells, suggesting activation of the Akt/PI3K pathway in these neurons. Intranasal insulin (InInsulin) reduced HI-induced sensorimotor behavioral disturbances at P11. InInsulin prevented HI-induced increased Fluoro-Jade C+ degenerated neurons, cleaved caspase 3+ neurons, and volume loss in the ipsilateral brain at P11. There was no sex-specific response to HI or insulin. The findings confirm that intranasal insulin provides neuroprotection against HI brain injury in P10 rats associated with activation of intracellular cell survival signaling. If further pre-clinical research shows long-term benefits, intranasal insulin has the potential to be a promising non-invasive therapy to improve outcomes for newborns with HIE. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Abhay Bhatt, Lir-Wan Fan has patent #“16/891,789; Compositions, Systems, and Methods for Treating or Reducing Hypoxia-Ischemia Induced Brain Damage and Neurobehavioral Dysfunction in Neonates.” to Lir-Wan Fan, Abhay Bhatt. Pending rebuttal to examiner response. (© 2024 The Authors.)
Databáze:	MEDLINE
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