Fetal brain injury in experimental intrauterine asphyxia and inflammation in Göttingen minipigs

Lyng, Kristin; Munkeby, Berit H.; Scheie, David; Mallard, Carina; Hagberg, Henrik; Stray‐Pedersen, Babill; Saugstad, Ola Didrik; Frøen, J. Frederik

doi:10.1515/jpm.2006.041

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…Neonatal infection and inflammation are also known to lead to neurodevelopmental impairment (Stoll et al, 2004;Mallard and Wang, 2012). Over the past years, studies involving animal models of fetal/neonatal inflammation have played a key role in elucidating mechanisms involved in preterm brain injury (Eklind et al, 2001;Lyng et al, 2006;Mallard and Hagberg, 2007;Wang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro evaluation of the effect of 2‐(4‐morpholinethyl)1‐phenylcyclohexanecarboxylate on inflammation‐sensitized hyperoxia‐induced developing brain injury

Posod

Krepp

Urbanek

et al. 2013

J of Neuroscience Research

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Supraphysiological oxygen concentrations are toxic to the developing brain. Inflammatory processes increase the risk for brain injury. Sigma-1 receptor agonists are potent suppressors of inflammation-related events and are powerful immunomodulatory and antioxidative agents. Neuroprotective effects of sigma-1 receptor agonists have been described previously for neonatal and adult models of brain injury. The aim of this study was to assess the selective sigma-1 receptor agonist 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084) in models of inflammation-sensitized hyperoxia-induced developing brain injury. For in vivo studies, rat pups were randomly presensitized with 1) lipopolysaccharide or 2) vehicle on postnatal day 3. On day 6, pups received either 1) PRE-084 or 2) vehicle and were subsequently exposed to hyperoxic conditions for 6, 12, or 24 hr. At the end of exposure, animals were sacrificed and brains were processed for caspase-3 analysis using immunohistochemistry and Western blotting. For in vitro studies, oligodendroglial cells were subjected to hyperoxic conditions in the presence or absence of proinflammatory cytokines and PRE-084. Cell membrane integrity and cell viability were assessed by means of lactate dehydrogenase and 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays. Inflammatory presensitization significantly increased hyperoxia-induced injury both in vivo and in vitro. PRE-084 administration did not attenuate damage. Sigma-1 receptor agonists have been described as a promising therapeutic strategy for brain injury. We were not able to confirm this in the present model. The exact mechanisms of action of sigma-1 receptor agonists as well as the pathophysiologic pathways involved in hyperoxia-induced injury in the developing brain remain to be elucidated.

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Section: Discussionmentioning

confidence: 99%

In vivo and in vitro evaluation of the effect of 2‐(4‐morpholinethyl)1‐phenylcyclohexanecarboxylate on inflammation‐sensitized hyperoxia‐induced developing brain injury

Posod

Krepp

Urbanek

et al. 2013

J of Neuroscience Research

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“…Ischemia/hypoxia is known to trigger microvascular inflammation [222,227]. Late gestational intrauterine asphyxia of minipigs results in microglial activation limited to the brainstem [228]. Microglial activation is associated with many toxic exposures [229].…”

Section: An Animal Model For Focal Inflammation Of the Ntsmentioning

confidence: 99%

Proposed Toxic and Hypoxic Impairment of a Brainstem Locus in Autism

McGinnis

Audhya

Edelson

2013

IJERPH

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Electrophysiological findings implicate site-specific impairment of the nucleus tractus solitarius (NTS) in autism. This invites hypothetical consideration of a large role for this small brainstem structure as the basis for seemingly disjointed behavioral and somatic features of autism. The NTS is the brain’s point of entry for visceral afference, its relay for vagal reflexes, and its integration center for autonomic control of circulatory, immunological, gastrointestinal, and laryngeal function. The NTS facilitates normal cerebrovascular perfusion, and is the seminal point for an ascending noradrenergic system that modulates many complex behaviors. Microvascular configuration predisposes the NTS to focal hypoxia. A subregion—the “pNTS”—permits exposure to all blood-borne neurotoxins, including those that do not readily transit the blood-brain barrier. Impairment of acetylcholinesterase (mercury and cadmium cations, nitrates/nitrites, organophosphates, monosodium glutamate), competition for hemoglobin (carbon monoxide, nitrates/nitrites), and higher blood viscosity (net systemic oxidative stress) are suggested to potentiate microcirculatory insufficiency of the NTS, and thus autism.

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The Pig as a Model Animal for Studying Cognition and Neurobehavioral Disorders

Gieling

Schuurman

Nordquist

et al. 2011

Current Topics in Behavioral Neurosciences

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In experimental animal research, a short phylogenetic distance, i.e., high resemblance between the model species and the species to be modeled is expected to increase the relevance and generalizability of results obtained in the model species. The (mini)pig shows multiple advantageous characteristics that have led to an increase in the use of this species in studies modeling human medical issues, including neurobehavioral (dys)functions. For example, the cerebral cortex of pigs, unlike that of mice or rats, has cerebral convolutions (gyri and sulci) similar to the human neocortex. We expect that appropriately chosen pig models will yield results of high translational value. However, this claim still needs to be substantiated by research, and the area of pig research is still in its infancy. This chapter provides an overview of the pig as a model species for studying cognitive dysfunctions and neurobehavioral disorders and their treatment, along with a discussion of the pros and cons of various tests, as an aid to researchers considering the use of pigs as model animal species in biomedical research.

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Fetal brain injury in experimental intrauterine asphyxia and inflammation in Göttingen minipigs

Cited by 4 publications

References 28 publications

In vivo and in vitro evaluation of the effect of 2‐(4‐morpholinethyl)1‐phenylcyclohexanecarboxylate on inflammation‐sensitized hyperoxia‐induced developing brain injury

In vivo and in vitro evaluation of the effect of 2‐(4‐morpholinethyl)1‐phenylcyclohexanecarboxylate on inflammation‐sensitized hyperoxia‐induced developing brain injury

Proposed Toxic and Hypoxic Impairment of a Brainstem Locus in Autism

The Pig as a Model Animal for Studying Cognition and Neurobehavioral Disorders

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