Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection

Autor: Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung-Ha Hong, Nicolas G. Bazan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-42126-w
Popis: Abstract Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in the subcortex. Additionally, the FFAs elicit a comprehensive downregulation of inflammatory microglia/monocyte-derived macrophages and astrocyte-associated genes in the subcortical region. Functional analysis reveals inhibition of immune-related pathways and production of upstream molecules related to detrimental signaling events in post-stroke acute and subacute phases.
Databáze: Directory of Open Access Journals
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