Chemokine and Inflammatory Cell Response to Hypoxia-Ischemia in Immature Rats

Bona, Elsa; Andersson, Anna-Lena; Blomgren, Klas; Gilland, Eric; Puka-Sundvall, Malgorzata; Gustafson, Katarina; Hagberg, Henrik

doi:10.1203/00006450-199904010-00008

Cited by 318 publications

(276 citation statements)

References 43 publications

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“…In agreement with previous reports [33,86,87] , our study indicates that ischemia triggers a strong inflammatory response that involves activation of endogenous glial cells and overexpression of various proinflammatory factors, including TNF-α, IL-1β, NO, iNOS, and COX-2, and contributes to delayed brain damage. Interestingly, huperzine A decreased overexpression of proinflammatory factors in the ipsilateral cortex and striatum, and huperzine A suppressed activation of astrocytes and microglia in the ischemic penumbra [48] .…”

Section: Acetylcholinesterase Inhibitorssupporting

confidence: 79%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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Section: Acetylcholinesterase Inhibitorssupporting

confidence: 79%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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“…a predominance of grey matter damage): (1) a hypoxic-ischaemic model produced by the combination of global hypoxia with a unilateral carotid artery ligation at postnatal day 7 in rats or day 9 in mice; 54,55 and (2) a model of excitotoxic brain damage produced by intracerebral injection of newborn mice or rats with the glutamatergic analogue ibotenate. 56,57 In the hypoxic-ischaemic model, systemic injection of low and non-injurious doses of a toll-like receptor (TLR) 4 or TLR3 agonist (Escherichia coli-derived lipopolysaccharide [LPS] or polyinosinic:polycytidylic acid, respectively), 4 hours before a typically non-injurious hypoxic-ischaemic insult (lasting 20min), induced massive hemispheric brain damage.…”

Section: Experimental Evidence Of Inflammation-induced Sensitization mentioning

confidence: 99%

Inflammation‐induced sensitization of the brain in term infants

Fleiss

Tann

Degos

et al. 2015

Develop Med Child Neuro

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COXPerinatal insults are a leading cause of infant mortality and amongst survivors are frequently associated with neurocognitive impairment, cerebral palsy (CP), and seizure disorders. The events leading to perinatal brain injury are multifactorial. This review describes how one subinjurious factor affecting the brain sensitizes it to a second injurious factor, causing an exacerbated injurious cascade. We will review the clinical and experimental evidence, including observations of high rates of maternal and fetal infections in term-born infants with neonatal encephalopathy and cerebral palsy. In addition, we will discuss preclinical evidence for the sensitizing effects of inflammation on injuries, such as hypoxia-ischaemia, our current understanding of the mechanisms underpinning the sensitization process, and the possibility for neuroprotection. PERINATAL BRAIN INJURY IN THE TERM-BORN INFANTIntrapartum neonatal deaths are the third leading cause of global childhood mortality. 1 In addition, each year perinatal insults are estimated to be responsible for more than one million new cases of neonatal encephalopathy, and nearly half a million infants with impairments such as cerebral palsy (CP).2 Infants exposed to a perinatal insult typically present with encephalopathy, a descriptive term for a clinical constellation of neurological dysfunctions in the term-born that includes difficulty with initiating and maintaining respiration; depression of tone and reflexes; subnormal levels of consciousness; and seizures.3 Whilst often assumed to result solely from acute intrapartum hypoxic-ischaemia, the precise contribution of hypoxia is likely to vary according to the definition of encephalopathy used, the range of competing risks, and the care setting. 3,4 Presumed hypoxia-ischaemia is diagnosed based on reduced Apgar scores and acidosis, 5 and the combination of progressive hypoxia, hypercarbia, and acidosis is often referred to as asphyxia. 6 Encephalopathy resulting from hypoxia-ischaemia can be clearly diagnosed only in a small number of cases in which a sentinel event, such as placental abruption, uterine rupture, cord prolapse, or shoulder dystocia, is clearly present. Clinical studies have identified a number of other important antepartum and intrapartum risk factors for neonatal encephalopathy. [7][8][9][10] In low-income settings, where access to skilled birth attendants and emergency obstetric intervention is often limited, the probability of intrapartum hypoxic events contributing to neonatal encephalopathy is increased.2,9,11 However, in general, neonatal encephalopathy is likely to be a multifactorial condition with complex aetiology, encompassing several causal events, with strong evidence that fetal exposure to infection contributes. 12 CONCEPT OF INFLAMMATION-INDUCED SENSITIZATIONAn increasingly common model for the complex and multifactorial process of perinatal brain injury involves sensitization, 13-15 whereby factors not severe enough by themselves to induce significant brain damage make the developi...

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“…Despite temporary but often incomplete restorations of phosphocreatine and ATP (Figs. 2 and 3), functional and anatomic mitochondrial integrity is compromised, owing primarily to a calcium (Ca ++ ) overload, initiated during the hypoxic-ischemic interval, and to the generation of oxygen reactive species (Bagenholm et al, 1998;Bona et al, 1999;Vannucci et al, 2001). These perturbations lead to an uncoupling of oxidative phosphorylation as well as to an activation of degradative enzymes, including phospholipases, proteases, and endonucleases, which activities cause widespread destruction of cellular and subcellular membranes and macromolecules (Vannucci, 1990).…”

Section: Discussionmentioning

confidence: 99%

Secondary Energy Failure after Cerebral Hypoxia–Ischemia in the Immature Rat

Vannucci

Towfighi

Vannucci

2004

J Cereb Blood Flow Metab

121

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Summary:A delayed or secondary energy failure occurs during recovery from perinatal cerebral hypoxia-ischemia. The question remains as to whether the energy failure causes or accentuates the ultimate brain damage or is a consequence of cell death. To resolve the issue, 7-day postnatal rats underwent unilateral common carotid artery occlusion followed thereafter by systemic hypoxia with 8% oxygen for 2.5 hours. During recovery, the brains were quick frozen and individually processed for histology and the measurements of 1) high-energy phosphate reserves and 2) neuronal (MAP-2, SNAP-25) and glial (GFAP) proteins. Phosphocreatine (PCr) and ATP, initially depleted during hypoxia-ischemia, were partially restored during the first 18 hours of recovery, with secondary depletions at 24 and 48 hours. During the initial recovery phase (6 to 18 hours), there was a significant correlation between PCr and the histology score (0 to 3), but not for ATP. During the late recovery phase, there was a highly significant correlation between all measured metabolites and the damage score. Significant correlation also exhibited between the neuronal protein markers, MAP-2 and SNAP-25, and PCr as well as the sum of PCr and Cr at both phases of recovery. No correlation existed between the high-energy reserves and the glial protein marker, GFAP. The close correspondence of PCr to histologic brain damage and the loss of MAP-2 and SNAP-25 during both the early and late recovery intervals suggest evolving cellular destruction as the primary event, which precedes and leads to the secondary energy failure.

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Chemokine and Inflammatory Cell Response to Hypoxia-Ischemia in Immature Rats

Cited by 318 publications

References 43 publications

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Inflammation‐induced sensitization of the brain in term infants

Secondary Energy Failure after Cerebral Hypoxia–Ischemia in the Immature Rat

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