Selective vulnerability in the developing central nervous system

McQuillen, Patrick S.; Ferriero, Donna M.

doi:10.1016/j.pediatrneurol.2003.10.001

Cited by 254 publications

(181 citation statements)

References 86 publications

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“…These factors, combined with a compensatory increase in cerebral blood flow and enhanced glucose extraction from the blood, may provide neuroprotection to the developing brain during hypoglycemia [21,37]. Differences in the developmental stage of the cells, the number and function of neurotransmitter receptors, molecular and biochemical pathways of energy metabolism, susceptibility to respiratory depression and glucose reperfusion injury may also be responsible for the age-related vulnerability during hypoglycemia [7,20,30,32]. Similar, age-related resistance of the early postnatal brain has been demonstrated in other models of perinatal injuries, such as hypoxia-ischemia [11,36].…”

Section: Discussionmentioning

confidence: 99%

Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain

et al. 2008

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Acute hypoglycemia is associated with neuronal injury in the mature human and rodent brains. Even though hypoglycemia is a common metabolic problem during development, its effects on the developing brain are not well understood. To characterize the severity of regional brain injury, postnatal day (P) 7, P14, P28 (N=20-30/age) and adult rats (N=8-12) were subjected to acute hypoglycemia of equivalent severity and duration (mean blood glucose concentration: 30.0±0.1 mg/ dL for 210 min). Neuronal injury in the cerebral cortex, striatum, hippocampus and hypothalamus was assessed 24 hr, 72 hr and 1 wk later by determining the number of degenerating cells positive for Fluoro-Jade B (FJB+) in the region. Compared with age-matched control, greater number of FJB + cells was present per brain section of P14, P28 and adult hypoglycemia groups (P<0.005, each). The cerebral cortex was more vulnerable than hippocampus and striatum at all three ages (P<0.01). Compared with P28 (131±21) and adult (171±21) rats, fewer FJB+ cells (39±6) per brain section were present in P14 hypoglycemic rats (P<0.01, each). Hypoglycemia was not associated with cell injury in P7 rats. FJB+ cells were absent in the hypothalamus in all four ages. Similar results were present 24 hr post-hypoglycemia, where as analysis at 1 wk demonstrated efficient clearing of FJB + cells in the brain regions of developing rats. Varying the duration of fasting did not alter the severity of regional cell injury. These results suggest that postnatal age influences the regional vulnerability to hypoglycemia-induced neuronal death in the rat brain.

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Section: Discussionmentioning

confidence: 99%

Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain

et al. 2008

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“…The developing brain is susceptible to reactive oxygen species-mediated injury due to imbalanced brain antioxidant defense, neuronal membranes rich in polyunsaturated fatty acids, a high rate of oxygen consumption, and high availability of free iron as reviewed in refs. (3)(4)(5). Together with a limited threshold for oxidative stress, central nervous system immaturity also provides for a more rapid accumulation of microglia, differences in release of cytokine and chemokine, and a developing complement system, all of which make inflammation an important contributor to both injury and repair after a hypoxic insult (4,6).…”

mentioning

confidence: 99%

“…(3)(4)(5). Together with a limited threshold for oxidative stress, central nervous system immaturity also provides for a more rapid accumulation of microglia, differences in release of cytokine and chemokine, and a developing complement system, all of which make inflammation an important contributor to both injury and repair after a hypoxic insult (4,6). The developing brain can be exposed to both hypoxia and subsequent hyperoxia in a resuscitation situation.…”

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confidence: 99%

Transcriptome profiling of the newborn mouse brain after hypoxia–reoxygenation: hyperoxic reoxygenation induces inflammatory and energy failure responsive genes

et al. 2013

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Background: Supplemental oxygen used during resuscitation can be detrimental to the newborn brain. The aim was to determine how different oxygen therapies affect gene transcription in a hypoxia-reoxygenation model. Methods: C57BL/6 mice (n = 56), postnatal day 7, were randomized either to 120 min of hypoxia 8% O 2 followed by 30 min of reoxygenation with 21, 40, 60, or 100% O 2 , or to normoxia followed by 30 min of 21 or 100% O 2 . Affymetrix 750k expression array was applied with RT-PCR used for validation. Histopathology and immunohistochemistry 3 d after hypoxiareoxygenation compared groups reoxygenated with 21 or 100% O 2 with normoxic controls (n = 22). results: In total, ~81% of the gene expression changes were altered in response to reoxygenation with 60 or 100% O 2 and constituted many inflammatory-responsive genes (i.e., C5ar2, Stat3, and Ccl12). Oxidative phosphorylation was downregulated after 60 or 100% O 2 . Iba1 + cells were significantly increased in the striatum and hippocampal CA1 after both 21 and 100% O 2 . conclusion: In the present model, hypoxia-reoxygenation induces microglial accumulation in subregions of the brain. The transcriptional changes dominating after applying hyperoxic reoxygenation regimes include upregulating genes related to inflammatory responses and suppressing the oxidative phosphorylation pathway.

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“…This results in a vascular border zone around the trigones and posterior horns of the lateral ventricles. Some believed that PVL is a result of selective vulnerability of cells of oligodendrocyte lineage to hypoxic-ischemic insult [12,13].…”

Section: ) What Are the Normal Signal Intensities Within The Brain? Wmentioning

confidence: 99%

“…Some injuries may only be apparent few days after the insult due to delayed apoptosis [16,17]. Signal abnormalities on diffusion-weighted images may be very subtle due to the intrinsically high T2 signal of the neonatal brain.…”

Section: ) What Are the Normal Signal Intensities Within The Brain? Wmentioning

confidence: 99%

Pediatric MRI Brain: Normal or abnormal, that is the question.

Tan¹

2017

Radiol Diagn Imaging

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Selective vulnerability in the developing central nervous system

Cited by 254 publications

References 86 publications

Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain

Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain

Transcriptome profiling of the newborn mouse brain after hypoxia–reoxygenation: hyperoxic reoxygenation induces inflammatory and energy failure responsive genes

Pediatric MRI Brain: Normal or abnormal, that is the question.

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