Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection
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.
Reid, Madigan M.; Belayev, Ludmila; Khoutorova, Larissa; Mukherjee, Pranab K.; Obenaus, Andre; Shelvin, Kierany; Knowles, Stacey; Hong, Sung Ha; and Bazan, Nicolas G., "Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection" (2023). School of Graduate Studies Faculty Publications. 145.