The Chilling Details

Verklan, M. Terese

doi:10.1097/01.jpn.0000346221.48202.7e

Cited by 58 publications

(17 citation statements)

References 35 publications

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“…Hypoxia induced direct brain injury which occurs in the acute hypoxic phase, and indirect brain injury appears after reoxygenation which is mainly attributed to inflammatory response induced by neuro-immunological activation under hypoxic conditions [25], [26]. Neuroinflammatory response in the CNS is a complicated process which involves numerous damage signals, cellular responses and alterations in the microenvironment [27], [28].…”

Section: Discussionmentioning

confidence: 99%

Astrocyte-Derived Proinflammatory Cytokines Induce Hypomyelination in the Periventricular White Matter in the Hypoxic Neonatal Brain

et al. 2014

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Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD), a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL) loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM) and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

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Section: Discussionmentioning

confidence: 99%

Astrocyte-Derived Proinflammatory Cytokines Induce Hypomyelination in the Periventricular White Matter in the Hypoxic Neonatal Brain

et al. 2014

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“…In this phase, the crucial event triggering a cascade of chain reactions is represented by ATP depletion secondary to anaerobic glycolysis and metabolic acidosis induced by hypoxia [8]. Reduced ATP availability determines the dysfunction of ATPase systems, in particular Na + , K + -ATPase and glial-ATPase.…”

Section: Mechanisms Of Cerebral Injurymentioning

confidence: 99%

“…Protease degrades neurofilaments and can determine cytoskeleton rupture with disintegration of the cellular body; phospholipase hydrolyzes phospholipids and can damage cellular membrane and induce the release of arachidonic acid with consequent production of vasodilator prostaglandins that give rise to reperfusion of ischemia (Figure 1). Furthermore, excessive amounts of glutamate can cause excitotoxicity leading to the death of neurons and glial cells [8]. …”

Section: Mechanisms Of Cerebral Injurymentioning

confidence: 99%

Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

Distefano

Praticò

2010

Ital J Pediatr

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Hypoxic-ischemic encephalopathy (HIE) is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant.Hypoxic-ischemic (H-I) injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter.This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

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“…Perinatal hypoxic-ischemic encephalopathy (HIE) is associated with high neonatal mortality and severe long-term neurologic morbidity (Fernandez-Lopez et al, 2014; Li et al, 2012; Ma and Zhang, 2015; Verklan, 2009; Yager and Ashwal, 2009). The molecular mechanisms and the pathway of brain injury in infants with HIE remain largely elusive.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of microRNA-210 provides neuroprotection in hypoxic–ischemic brain injury in neonatal rats

Dasgupta

et al. 2016

Neurobiology of Disease

105

142

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Perinatal hypoxic-ischemic encephalopathy (HIE) is associated with high neonatal mortality and severe long-term neurologic morbidity. Yet the mechanisms of brain injury in infants with HIE remain largely elusive. The present study determined a novel mechanism of microRNA-210 (miR-210) in silencing endogenous neuroprotection and increasing hypoxicischemic brain injury in neonatal rats. The study further revealed a potential therapeutic effect of miR-210 inhibition using complementary locked nucleic acid oligonucleotides (miR-210-LNA) in 10-day-old neonatal rats in the Rice-Vannucci model. The underlying mechanisms were investigated with intracerebroventricular injection (i.c.v) of miR-210 mimic, miR-210-LNA, glucocorticoid receptor (GR) agonist and antagonist. Luciferase reporter gene assay was conducted for identification of miR-210 targeting GR 3’untranslated region. The results showed that the HI treatment significantly increased miR-210 levels in the brain, and miR-210 mimic significantly decreased GR protein abundance and exacerbated HI brain injury in the pups. MiR-210-LNA administration via i.c.v. 4 hours after the HI insult significantly decreased brain miR-210 levels, increased GR protein abundance, reduced HI-induced neuronal death and brain infarct size, and improved long-term neurological function recovery. Of importance, the intranasal delivery of miR-210-LNA 4 hours after the HI insult produced similar effects in decreasing HI-induced neonatal brain injury and improving neurological function later in life. Altogether, the present study provides evidence of a novel mechanism of miR-210 in a neonatal HI brain injury model, and suggests a potential therapeutic approach of miR-210 inhibition in the treatment of neonatal HIE.

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The Chilling Details

Cited by 58 publications

References 35 publications

Astrocyte-Derived Proinflammatory Cytokines Induce Hypomyelination in the Periventricular White Matter in the Hypoxic Neonatal Brain

Astrocyte-Derived Proinflammatory Cytokines Induce Hypomyelination in the Periventricular White Matter in the Hypoxic Neonatal Brain

Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

Inhibition of microRNA-210 provides neuroprotection in hypoxic–ischemic brain injury in neonatal rats

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