Heme oxygenase-1 induction in the brain during lipopolysaccharide-induced acute inflammation

Miyagawa, Shigeru; Nakatsuka, Ichiro; Hayashi, Yusuke; Higuchi, Hitoshi; Shimada, Masahiko; Miyawaki, Takuya

doi:10.2147/ndt.s3063

Cited by 21 publications

(7 citation statements)

References 24 publications

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“…1d). Our findings are similar to results obtained in adult animals, in which a subseptic dose of LPS induced HO-1 mRNA in the hippocampus and hypothalamus (Maeda et al 2008). HO-1 is also induced in other highly vascularized tissues, such as heart and lung by systemic LPS (Wiesel et al 2000).…”

Section: Discussionsupporting

confidence: 91%

Expression of the Nrf2‐system at the blood‐CSF barrier is modulated by neonatal inflammation and hypoxia‐ischemia

D’Angelo

Sandberg

et al. 2012

J of Inher Metab Disea

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Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant systems shown to play a neuroprotective role in the adult by preserving blood–brain barrier function. The choroid plexus, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2-and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia-ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti-oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxidant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia-ischemia.

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Section: Discussionsupporting

confidence: 91%

Expression of the Nrf2‐system at the blood‐CSF barrier is modulated by neonatal inflammation and hypoxia‐ischemia

D’Angelo

Sandberg

et al. 2012

J of Inher Metab Disea

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“…Further, strong induction of HO-1, detectable with western blot analysis, is usually highest at time points less than 24 h after stress (hyperthermia, ischemia, etc.) [49,50]. Therefore, the finding in the present study, that HO-1 dot blot analysis of total brain homogenate from aged animals undergoing chronic rather than acute stress shows insignificant differences, is not unexpected.…”

Section: Discussionsupporting

confidence: 63%

Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease

Siedlak¹,

Casadesús

Webber³

et al. 2009

Free Radical Research

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Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer’s, Parkinson’s and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit.

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“…with LPS (2 mg/kg; E.coli 055 B5) [30,31] or vehicle (saline 0.9%), once per day, on postnatal days 25-28 to mimic a severe infection state [32]. …”

Section: Methodsmentioning

confidence: 99%

N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups

et al. 2013

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Background and AimsGlutaric aciduria type I (GA-I) is characterized by accumulation of glutaric acid (GA) and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS) in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC) on theses markers.MethodsRat pups were injected with GA (5umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150mg/kg/day; intragastric gavage; for the same period). LPS (2mg/kg; E.coli 055 B5) or vehicle (saline 0.9%) was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed.ResultsGA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance) content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers.ConclusionsThese results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could represent a possible adjuvant therapy in treatment of children with GA-I.

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Heme oxygenase-1 induction in the brain during lipopolysaccharide-induced acute inflammation

Cited by 21 publications

References 24 publications

Expression of the Nrf2‐system at the blood‐CSF barrier is modulated by neonatal inflammation and hypoxia‐ischemia

Expression of the Nrf2‐system at the blood‐CSF barrier is modulated by neonatal inflammation and hypoxia‐ischemia

Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease

N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups

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