Ischemia reduces inter‐alpha inhibitor proteins in the brain of the ovine fetus

Spasova, Mariya S; Chen, Xiaodi; Sadowska, Grazyna B.; Horton, Edward R.; Lim, Yow‐Pin; Stonestreet, Barbara S.

doi:10.1002/dneu.22451

Cited by 12 publications

(30 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it is important to emphasize that in our previous study in fetal sheep, we did not have values beyond 48 h after ischemia. Therefore, we cannot rule out the possibility that IAIP levels in the brain might have increased at a later time point because we observed a normalization of the values by 24 and 48 h after ischemia (Spasova et al, 2016).…”

Section: Discussionmentioning

confidence: 93%

“…Both the major moieties of IAIPs, IαI and PαI , were detected by Western immunoblot (Figs. 2 and 3) (Spasova et al, 2014; Spasova et al, 2016). IαI was higher ( P ≪ 0.001 ) in ipsilateral damaged cerebral cortices 24 h after HI compared with the right cerebral cortex in the sham control group (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These findings suggest that ischemia is associated with increased IAIP utilization and/or decreased production in the CNS (Spasova et al, 2016). Nonetheless, brain ischemia in the fetal sheep did not result in alterations in plasma concentrations of IAIPs (Spasova et al, 2016). Therefore, IAIPs represent endogenous anti‐inflammatory molecules that could be regulated in the brain during injury related events.…”

Section: Introductionmentioning

confidence: 99%

“…The ubiquitous presence of endogenous IAIPs in numerous types of brain cells and brain regions in the central nervous system (CNS) of rodents suggests that endogenous IAIPs represent an important, but previously unrecognized constituent of the normal brain composition, and most likely function (Chen et al, 2016; Spasova et al, 2014). In addition, we have previously shown that IAIP expression is reduced shortly after ischemia in the cerebral cortex and cerebellum of fetal sheep and returns toward non‐ischemic levels between 24 and 48 h after an ischemic insult (Spasova et al, 2016). These findings suggest that ischemia is associated with increased IAIP utilization and/or decreased production in the CNS (Spasova et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, we have previously shown that IAIP expression is reduced shortly after ischemia in the cerebral cortex and cerebellum of fetal sheep and returns toward non‐ischemic levels between 24 and 48 h after an ischemic insult (Spasova et al, 2016). These findings suggest that ischemia is associated with increased IAIP utilization and/or decreased production in the CNS (Spasova et al, 2016). Nonetheless, brain ischemia in the fetal sheep did not result in alterations in plasma concentrations of IAIPs (Spasova et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Alterations in inter‐alpha inhibitor protein expression after hypoxic‐ischemic brain injury in neonatal rats

Disdier

Zhang

Fukunaga

et al. 2017

Intl J of Devlp Neuroscience

Self Cite

View full text Add to dashboard Cite

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full-term birth-related complications that reflect widespread damage to cerebral cortical structures. Inflammation has been implicated in the long-term evolution and severity of HI brain injury. Inter-Alpha Inhibitor Proteins (IAIPs) are immune modulator proteins that are reduced in systemic neonatal inflammatory states. We have shown that endogenous IAIPs are present in neurons, astrocytes and microglia and that exogenous treatment with human plasma purified IAIPs decreases neuronal injury and improves behavioral outcomes in neonatal rats with HI brain injury. In addition, we have shown that endogenous IAIPs are reduced in the brain of the ovine fetus shortly after ischemic injury. However, the effect of HI on changes in circulating and endogenous brain IAIPs has not been examined in neonatal rats. In the current study, we examined changes in endogenous IAIPs in the systemic circulation and brain of neonatal rats after exposure to HI brain injury. Postnatal day 7 rats were exposed to right carotid artery ligation and 8% oxygen for 2h. Sera were obtained immediately, 3, 12, 24, and 48h and brains 3 and 24h after HI. IAIPs levels were determined by a competitive enzyme-linked immunosorbent assay (ELISA) in sera and by Western immunoblots in cerebral cortices. Serum IAIPs were decreased 3h after HI and remained lower than in non-ischemic rats up to 7days after HI. IAIP expression increased in the ipsilateral cerebral cortices 24h after HI brain injury and in the hypoxic contralateral cortices. However, 3h after hypoxia alone the 250kDa IAIP moiety was reduced in the contralateral cortices. We speculate that changes in endogenous IAIPs levels in blood and brain represent constituents of endogenous anti-inflammatory neuroprotective mechanism(s) after HI in neonatal rats.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Alterations in inter‐alpha inhibitor protein expression after hypoxic‐ischemic brain injury in neonatal rats

Disdier

Zhang

Fukunaga

et al. 2017

Intl J of Devlp Neuroscience

Self Cite

View full text Add to dashboard Cite

show abstract

Ontogeny of inter‐alpha inhibitor protein (IAIP) expression in human brain

Kim

Monte

Hovanesian

et al. 2019

J of Neuroscience Research

Self Cite

View full text Add to dashboard Cite

Inter‐alpha inhibitor proteins (IAIPs) are naturally occurring immunomodulatory molecules found in most tissues. We have reported ontogenic changes in the expression of IAIPs in brain during development in sheep and abundant expression of IAIPs in fetal and neonatal rodent brain in a variety of cellular types and brain regions. Although a few studies identified bikunin, light chain of IAIPs, in adult human brain, the presence of the complete endogenous IAIP protein complex has not been reported in human brain. In this study, we examined the immunohistochemical expression of endogenous IAIPs in human cerebral cortex from early in development through the neonatal period and in adults using well‐preserved postmortem brains. We examined total, nuclear, and cytoplasmic staining of endogenous IAIPs and their expression in neurofilament light polypeptide–positive neurons and glial fibrillary acidic protein (GFAP)–positive astrocytes. IAIPs were ubiquitously detected for the first time in cerebral cortical cells at 24–26, 27–28, 29–36, and 37–40 weeks of gestation and in adults. Quantitative analyses revealed that IAIPs were predominately localized in the nucleus in all age groups, but cytoplasmic IAIP expression was more abundant in adult than in the younger ages. Immunoreactivity of IAIPs was expressed in neurons and astrocytes in all age groups. In addition, IAIP co‐localization with GFAP‐positive astrocytes was more abundant in adults than in the developing brain. We conclude that IAIPs exhibit ubiquitous expression, and co‐localize with neurons and astrocytes in the developing and adult human brain suggesting a potential role for IAIPs in development and endogenous neuroprotection.

show abstract

Endothelial Progenitor Cells Modulate Inflammation-Associated Stroke Vasculome

Acosta

Lee

Nguyen

et al. 2019

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Stroke remains a major unmet clinical need that warrants novel therapies. Following an ischemic insult, the cerebral vasculature secretes inflammatory molecules, creating the stroke vasculome profile. The present study evaluated the therapeutic effects of endothelial cells on the inflammation-associated stroke vasculome. qRT-PCR analysis revealed that specific inflammation-related vasculome genes BRM, IκB, Foxf1, and ITIH-5 significantly upregulated by oxygen glucose deprivation (OGD. Interestingly, co-culture of human endothelial cells (HEN6) with human endothelial cells (EPCs) during OGD significantly blocked the elevations of BRM, IκB, and Foxf1, but not ITIH-5. Next, employing the knockdown/antisense technology, silencing the inflammation-associated stroke vasculome gene, IκB, as opposed to scrambled knockdown, blocked the EPC-mediated protection of HEN6 against OGD. In vivo, stroke animals transplanted with intracerebral human EPCs (300,000 cells) into the striatum and cortex 4 h post ischemic stroke displayed significant behavioral recovery up to 30 days post-transplantation compared to vehicle-treated stroke animals. At 7 days post-transplantation, quantification of the fluorescent staining intensity in the cortex and striatum revealed significant upregulation of the endothelial marker RECA1 and a downregulation of the stroke-associated vasculome BRM, IKB, Foxf1, ITIH-5 and PMCA2 in the ipsilateral side of cortex and striatum of EPC-transplanted stroke animals relative to vehicle-treated stroke animals. Altogether, these results demonstrate that EPCs exert therapeutic effects in experimental stroke possibly by modulating the inflammation-plagued vasculome.

show abstract

Ischemia reduces inter‐alpha inhibitor proteins in the brain of the ovine fetus

Cited by 12 publications

References 81 publications

Alterations in inter‐alpha inhibitor protein expression after hypoxic‐ischemic brain injury in neonatal rats

Alterations in inter‐alpha inhibitor protein expression after hypoxic‐ischemic brain injury in neonatal rats

Ontogeny of inter‐alpha inhibitor protein (IAIP) expression in human brain

Endothelial Progenitor Cells Modulate Inflammation-Associated Stroke Vasculome

Contact Info

Product

Resources

About