Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts

Grow, Jennifer L.; Barks, John

doi:10.1016/s0095-5108(02)00059-3

Cited by 117 publications

(87 citation statements)

References 124 publications

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“…After the pups had remained in the hypoxic environment for 30 min, they were returned to their dam until they were killed. In this model, CBF in the hemisphere ipsilateral to the carotid ligation did not decrease by the ligation alone because of the contralateral supply of blood via the circle of Willis, but it did decrease during hypoxia and was restored immediately after the cessation of the hypoxic insult, which we refer to as reoxygenation hereafter (Grow and Barks, 2002).…”

Section: Methodsmentioning

confidence: 87%

“…Because the brain of the 7-d-old rat is developmentally similar to that of the human fetus or newborn infant at the third trimester, this rat model (Grow and Barks, 2002) and similar mouse models (Sheldon et al, 1998) well represent human neonatal HIE. In the rat model, cerebral blood flow (CBF) in the hemisphere ipsilateral to the carotid ligation decreased during hypoxia, but was restored immediately after the cessation of the hypoxic insult (Grow and Barks, 2002). Investigations using these rodent models revealed that proinflammatory molecules including cytokines (Hedtjarn et al, 2005a,b) and prostaglandin (PG) (Nogawa et al, 1997;Manabe et al, 2004), along with activated microglia/macrophages (Kim et al, 2003;Hedtjarn et al, 2004), are involved in the pathogenesis of HIE.…”

Section: Introductionmentioning

confidence: 98%

“…Toward an understanding of the mechanism involved in neonatal HIE, a number of studies using a rat model for HIE (i.e., 7-d-old rats subjected to carotid ligation combined with hypoxia) were conducted previously (Rice et al, 1981;Vannucci et al, 1999). Because the brain of the 7-d-old rat is developmentally similar to that of the human fetus or newborn infant at the third trimester, this rat model (Grow and Barks, 2002) and similar mouse models (Sheldon et al, 1998) well represent human neonatal HIE. In the rat model, cerebral blood flow (CBF) in the hemisphere ipsilateral to the carotid ligation decreased during hypoxia, but was restored immediately after the cessation of the hypoxic insult (Grow and Barks, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Prostaglandin D₂Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Taniguchi¹,

Mohri²,

Okabe-Arahori³

et al. 2007

J. Neurosci.

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Prostaglandin D 2 (PGD) is synthesized by hematopoietic PGD synthase (HPGDS) or lipocalin-type PGDS (L-PGDS), depending on the organ in which it is produced, and binds specifically to either DP 1 or DP 2 receptors. We investigated the role of PGD 2 in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonatal mice at postnatal day 7. In wild-type mice, hypoxia-ischemia increased PGD 2 production in the brain up to 90-fold compared with the level in sham-operated brains at 10 min after cessation of hypoxia. Whereas the size of the infarct was not changed in L-PGDS or DP 2 knock-out mouse brains compared with that in the wild-type HIE brains, it was significantly increased in HPGDS-L-PGDS double knock-out or DP 1 knock-out mice. The PGD 2 level in L-PGDS, HPGDS, and HPGDS-L-PGDS knock-out mice at 10 min of reoxygenation was 46, 7, and 1%, respectively, of that in the wild-type ones, indicating the infarct size to be in inverse relation to the amount of PGD 2 production. DP 1 receptors were exclusively expressed in endothelial cells after 1 h of reoxygenation, and cerebral blood flow decreased more rapidly after the onset of hypoxia and did not return to the baseline level after reoxygenation in HPGDS-L-PGDS knock-out mice. Endothelial cells were severely damaged in HPGDS-L-PGDS and DP 1 knock-out mice after 1 h of reoxygenation. In the human neonatal HIE brain, HPGDS-positive microglia were increased in number. In conclusion, it is probable that PGD 2 protected the neonatal brain from hypoxic-ischemic injury mainly via DP 1 receptors by preventing endothelial cell degeneration.

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Section: Methodsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prostaglandin D₂Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Taniguchi¹,

Mohri²,

Okabe-Arahori³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

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“…It is well accepted that depletion of cellular stores of high-energy phosphates, principally ATP and phosphocreatine, initiates the cascade of events leading to neuronal death after hypoxic ischemia. 3,4 On the basis of extensive animal studies, there is increasing evidence suggesting that mild or moderate brain hypothermia is an effective intervention to ameliorate the neuronal injury due to hypoxic ischemia. [5][6][7] A few small clinical trials have demonstrated the safety of head cooling when used in neonates with HIE.…”

Section: Introductionmentioning

confidence: 99%

“…We speculate that the use of phenobarbital may help to reduce cerebral metabolism and oxygen consumption 25 and facilitate the hypothermia process, which might enhance the neuroprotection of head cooling for infants with perinatal asphyxia. Although it remains controversial whether using high-dose phenobarbital alone is neuroprotective in asphyxiated infants, 4,26 prophylactic use of a conventional dose of phenobarbital for a few days in asphyxiated infants remains a common practice in China. On the other hand, routine use of dopamine for asphyxiated term infants is not a common practice.…”

mentioning

confidence: 99%

Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit

Zl¹,

et al. 2006

J Perinatol

118

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Objective: The objective of this study was to determine the efficacy of mild hypothermia via selective head cooling as a neuroprotective therapy in term infants with perinatal asphyxia.Study design: Full-term newborns who had 5 min Apgar scores <6, first arterial blood gas pH<7.10 or BD>15 mEq/l, and with the clinical signs of encephalopathy were enrolled within 6 h after birth. Patients were randomized to receive mild hypothermia treatment via selective head cooling for a total of 72 h or receive routine treatment as a control. Brain hypoxic-ischemic injury was quantified based on the head computed tomographic scan (CT scan) at postnatal age 5-7 days and a Neonatal Behavioral Neurological Assessment (NBNA) score at 7-10 days of life.Results: A total of 58 patients (30 hypothermia, 28 control) completed the study. Hypothermia was well tolerated in this study and attenuated the hypoxic-ischemic brain injury due to perinatal asphyxia. Head CT scan demonstrated moderate to severe hypoxic-ischemic changes in only 4/30 cases from the hypothermic group. In contrast, 18/28 cases in the control group showed moderate to severe hypoxic-ischemic changes (w 2 ¼ 15.97, P<0.01). Brain hypothermia also significantly improved the NBNA score (32±2 in the hypothermic group vs 28±3 in the control group, P<0.01). Conclusions:Our results suggest that selective head cooling may be used as a neuroprotective therapy in term neonates with perinatal asphyxia. A long-term follow-up study is needed to further validate the results of this study.

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bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

Wang

Xue

et al. 2020

Brain and Behavior

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Introduction Neonatal hypoxia–ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive. Methods We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen–glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL‐1β was examined in bFGF knockdown condition. IL‐1β knockout (KO) rats were generated using CRISPR/Cas9‐mediated technologies. We used an accepted rat model of HI, to assess the effect of IL‐1β deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level. Results We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin‐1β (IL‐1β). IL‐1β was up‐regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD‐mediated pathways. We found HI resulted in up‐regulation of IL‐1β mRNA in cortex and hippocampus. IL‐1β KO rats markedly attenuated the impairment of long‐term learning and memory induced by HI. Meanwhile, IL‐1β −/− (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up‐regulated in IL‐1β KO rats. Conclusions We showed that IL‐1β‐mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.

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Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts

Cited by 117 publications

References 124 publications

Prostaglandin D₂Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Prostaglandin D₂Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit

bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

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Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts

Cited by 117 publications

References 124 publications

Prostaglandin D2Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Prostaglandin D2Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit

bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration

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Prostaglandin D₂Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury

Prostaglandin D₂Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury