Bcl‐2 family members make different contributions to cell death in hypoxia and/or hyperoxia in rat cerebral cortex

Hu, Xiaoming; Qiu, Jingxin; Grafe, Marjorie R.; Rea, Harriett C.; Rassin, David K.; Perez‐Polo, J. Regino

doi:10.1016/s0736-5748(03)00089-3

Cited by 36 publications

(39 citation statements)

References 31 publications

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“…Bcl-2 is an anti-apoptotic protein present at relatively high levels in the neonatal brain and declines significantly in the postnatal brain (Abe-Dohmae et al, 1993). The expression of Bcl-2 in neonatal brain injury remains unclear (Akhtar et al, 2004;Hagberg, 2004), as several studies have shown that Bcl-2 levels may not be elevated in rodent models of neonatal brain injury (Chen et al, 2001;Northington et al, 2001), whereas others have reported contrary results (Ferrer et al, 1997;Hu et al, 2003;Nunez and McCarthy, 2004). One study reported that Bcl-2 was expressed in normal neurons, but that the expression was decreased in apoptotic neurons and further decreased in necrotic neurons following neonatal hypoxia-ischemia (Ferrer at al., 1997).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia–ischemia in rats

et al. 2007

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Neonatal hypoxia-ischemia (HI) is an important clinical problem with few effective treatments. Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of the hematopoietic system that has been shown to be neuroprotective in focal ischemia in vivo, and is currently in phase I/II clinical trials for ischemic stroke in humans. We tested G-CSF in a rat model of neonatal hypoxia-ischemia in postnatal day 7 unsexed rat pups. Three groups of animals were used: hypoxia ischemia (HI, n=67), hypoxia-ischemia with G-CSF treatment (HI+G, n=65), and healthy control (C, n=53). G-CSF (50 μg/kg, subcutaneous) was administered 1 hour after HI, and given on four subsequent days (five total injections). Animals were euthanized 24 hours, 1, 2, and 3 weeks after HI. Assessment included brain weight, histology, immunohistochemistry, and Western blotting. G-CSF treatment was associated with improved quantitative brain weight and qualitative Nissl histology after hypoxia-ischemia. TUNEL demonstrated reduced apoptosis in group HI+G. Western blot demonstrated decreased expression of Bax and cleaved caspase 3 in group HI+G. G-CSF treatment was also associated with increased expression of STAT3, Bcl-2, and Pim-1, all of which may have participated in the anti-apoptotic effect of the drug. We conclude that G-CSF ameliorates hypoxic-ischemic brain injury, and that this may occur in part by an inhibition of apoptotic cell death.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia–ischemia in rats

et al. 2007

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“…The animals of the HHI group were subsequently subjected to 100% oxygen for 120 min. A more detailed description of this procedure can be found elsewhere (Rice et al, 1981;Grafe, 1994Grafe, , 2008Hu et al, 2003Hu et al, , 2005Hu et al, , 2006.…”

Section: Materials and Methods Animals And Injury Modelmentioning

confidence: 99%

“…A rationale for the worsening outcome after the hyperoximic treatment was suggested by Hu et al (2003), who followed three apoptotic markers (cytoplasmic histone/DNA, caspase 3 activities, and Klenow fragments) after HI and HHI and found that hyperoximia induced an additional apoptotic pathway to the one induced by HI. Also, hyperoximia decreased CBF by 10-30% (Kety and Schmidt 1946;Rostrup et al, 1995;Watson et al, 2000;Nishimura et al, 2007;Zaharchuk et al, 2008), perhaps due to vasoconstriction (Nakajima et al, 1983;Watson et al, 2000).…”

Section: Injury After Hhimentioning

confidence: 99%

“…It has been reported that in experimental perinatal hypoxia, acute hyperoximic treatment exacerbates the initial injury (Munkeby et al, 2004;Shimabuku et al, 2005). Hu et al (2003) reported that hyperoximia in rats triggers an additional apoptotic signaling pathway when compared to hypoxia alone. Also, elevated blood oxygen levels, as they occur during hyperoximia, decrease cerebral blood flow (Kety and Schmidt, 1946;Leahy et al, 1980;Lundstrom et al, 1995), which in turn exacerbates hypoxia-induced ischemic injury.…”

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confidence: 99%

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Normobaric hyperoximia increases hypoxia‐induced cerebral injury: DTI study in rats

Bockhorst

Narayana

Dulin

et al. 2009

J of Neuroscience Research

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Perinatal hypoxia affects normal neurological development and can lead to motor, behavioral and cognitive deficits. A common acute treatment for perinatal hypoxia is oxygen resuscitation (hyperoximia), a controversial treatment. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), was performed in a P7 rat model of perinatal hypoxia to determine the effect of hyperoximia. These studies were performed on two groups of animals: 1) animals which were subjected to ischemia followed by hypoxia (HI), and 2) HI followed by hyperoximic treatment (HHI). Lesion volumes on high resolution MRI and DTI derived measures, fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities (lambda(l) and lambda(t), respectively) were measured in vivo one day, one week, and three weeks after injury. Most significant differences in the MRI and DTI measures were found at three weeks after injury. Specifically, three weeks after HHI injury resulted in significantly larger hyperintense lesion volumes (95.26 +/- 50.42 mm(3)) compared to HI (22.25 +/- 17.62 mm(3)). The radial diffusivity lambda(t) of the genu of corpus callosum was significantly larger in HHI (681 +/- 330 x 10(-6) mm(2)/sec) than in HI (486 +/- 96 x 10(-6) mm(2)/sec). Over all, most significant differences in all the DTI metrics (FA, MD, lambda(t), lambda(l)) at all time points were found in the corpus callosum. Our results suggest that treatment of perinatal hypoxia with normobaric oxygen does not ameliorate, but exacerbates damage.

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“…As discussed above, this may have been due to an uncoupling of cerebral blood fl ow and cerebral oxygen consumption resulting in excess delivery of O 2 to the brain. Less marked increases in O 2 delivery to the brain have been associated with neuronal apoptosis [43,44] as well as increased lipid peroxidation indicative of free radical damage to cell membranes [45,46] . Previous studies have shown that ischemic/hypoxic brain injury in experimental animals is minimal when body temperature is allowed to decrease spontaneously but increases when the decrease in body temperature is prevented [7][8][9][10] .…”

Section: Pathophysiological Implications Of Warming Hypoxic Infantsmentioning

confidence: 99%

Effect of Body Warming on Regional Blood Flow Distribution in Conscious Hypoxic One-Month-Old Rabbits

Seifert

Anna²,

Rohlicek

2006

Neonatology

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Background: Previous experiments have shown that warming hypoxic infants reduces total peripheral vascular resistance. This suggests that the usual vasoconstriction of less essential vascular beds during hypoxia may be reduced and that the normal redistribution of blood flow to more vital organs may be compromised. Objective:Evaluate the effect of body warming during hypoxia on the distribution of blood flow. Methods: The fluorescent microsphere technique was used to compare regional blood flow in 1-month-old rabbits during systemic hypoxia (10% inspired O₂) with (n = 9) and without (n = 10) body warming. Blood flow was measured in brain, stomach, small intestine, hindlimb muscle, skin, and kidneys. Arterial blood pressure, whole-body O₂ consumption, arterial blood O₂ saturation and blood gases were also measured. Measurements and Main Results: In hypoxia all animals decreased body temperature (–2°C). With hypoxia blood flow increased to brain and hindlimb muscle; decreased to stomach, small intestine, and kidneys, and was unchanged in skin. The increase in brain-blood flow maintained O₂ delivery at normoxic levels. Rewarming to the normoxic body temperature significantly changed blood flow in hypoxia. Brain blood flow increased by 102 ± 30% (mean ± SEM) thereby increasing O₂ delivery by 50 ± 23% above normoxic values. Blood flow also increased to skin, stomach, and small intestine. However, O₂ delivery to these tissues remained below normoxic levels. Conclusions: Warming during hypoxia may impose an additional cardiovascular demand. The changes in the pattern of blood flow distribution with mild warming during hypoxia support the hypothesis that warming represents a significant heat stress.

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Bcl‐2 family members make different contributions to cell death in hypoxia and/or hyperoxia in rat cerebral cortex

Cited by 36 publications

References 31 publications

Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia–ischemia in rats

Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia–ischemia in rats

Normobaric hyperoximia increases hypoxia‐induced cerebral injury: DTI study in rats

Effect of Body Warming on Regional Blood Flow Distribution in Conscious Hypoxic One-Month-Old Rabbits

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