Inter-alpha Inhibitor Proteins Modulate Neuroinflammatory Biomarkers After Hypoxia-Ischemia in Neonatal Rats
Year: 2019
Type: article
Abstract: Neuroinflammation contributes to hypoxic-ischemic (HI) brain injury. Inter-alpha inhibitor proteins (IAIPs) have important immunomodulatory properties. Human (h) plasma-derived IAIPs reduce brain injury and improve neurobehavioral outcomes after HI. However, the effects of hIAIPs on neuroinflammatory biomarkers after HI have not been examined. We determined whether hIAIPs attenuated HI-related neuroinflammation. Postnatal day-7 rats exposed to sham-placebo, or right carotid ligation and 8% oxygen for 90 minutes with placebo, and hIAIP treatment were studied. hIAIPs (30 mg/kg) or PL was injected intraperitoneally immediately, 24, and 48 hours after HI. Rat complete blood counts and sex were determined. Brain tissue and peripheral blood were prepared for analysis 72 hours after HI. The effects of hIAIPs on HI-induced neuroinflammation were quantified by image analysis of positively stained astrocytic (glial fibrillary acid protein [GFAP]), microglial (ionized calcium binding adaptor molecule-1 [Iba-1]), neutrophilic (myeloperoxidase [MPO]), matrix metalloproteinase-9 (MMP9), and MMP9-MPO cellular markers in brain regions. hIAIPs reduced quantities of cortical GFAP, hippocampal Iba-1-positive microglia, corpus callosum MPO, and cortical MMP9-MPO cells and the percent of neutrophils in peripheral blood after HI in male, but not female rats. hIAIPs modulate neuroinflammatory biomarkers in the neonatal brain after HI and may exhibit sex-related differential effects.
DOI: 10.1093/jnen/nlz051
Authors: Adriel Barrios-Anderson, Xiaodi Chen, Sakura Nakada, Ray Chen, Yow-Pin Lim, Barbara S Stonestreet
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Cytokines and the blood-brain barrier in the ovine fetus, COBRE for Perinatal Biology, COBRE for Reproductive Health, Inter-alpha Inhibitors in Hypoxic-Ischemic Brain Injury, Beneficial Effects of Inter-alpha Inhibitors in Fetal Brain Injury, Inter-alpha inhibitors: Novel neuroinflammatory modulator of neonatal brain injury
OpenAlex ID: W2954863426