Systemic G-CSF treatment does not improve long-term outcomes after neonatal hypoxic–ischaemic brain injury

Schlager, Gerald; Griesmaier, Elke; Wegleiter, K; Neubauer, Vera; Urbanek, M; Kiechl‐Kohlendorfer, Ursula; Felderhoff‐Mueser, Ursula; Keller, Matthias

doi:10.1016/j.expneurol.2010.11.021

Cited by 29 publications

(26 citation statements)

References 62 publications

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“…Previous studies have shown that G-CSF is effective in treating cardiac damage induced by ischemia reperfusion and cerebral ischemia [33,34]. However, G-CSF does not improve in all tissues or types of injury [35]. While G-CSF may acutely mobilize cells, here we evaluated the ability of G-CSF to mobilize BMDSCs that remain engrafted in the uterus after ischemia/reperfusion injury.…”

Section: Du Naqvi and Taylor Discussionmentioning

confidence: 96%

Ischemia/Reperfusion Injury Promotes and Granulocyte-Colony Stimulating Factor Inhibits Migration of Bone Marrow-Derived Stem Cells to Endometrium

Naqvi²,

Taylor³

2012

Stem Cells and Development

114

111

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Section: Du Naqvi and Taylor Discussionmentioning

confidence: 96%

Ischemia/Reperfusion Injury Promotes and Granulocyte-Colony Stimulating Factor Inhibits Migration of Bone Marrow-Derived Stem Cells to Endometrium

Naqvi²,

Taylor³

2012

Stem Cells and Development

114

111

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“…Our EPM finding is in agreement with previous studies that report increased anxiety in neonates (PND 13), young adult or aged rodents following perinatal asphyxia (Hoeger et al, 2000; Morales et al, 2010; Weitzdoerfer et al, 2004). However, no significant changes in anxiety were found in young adult rats that had been exposed to neonatal HI (Arteni et al, 2010; Schlager et al, 2011). Some possible reasons why this discrepancy in findings might be observed include methodological differences between the studies.…”

Section: Discussionmentioning

confidence: 99%

“…Some possible reasons why this discrepancy in findings might be observed include methodological differences between the studies. Specifically, in Schlager and colleagues (2011) the index of anxiety being used was the percentage of time spent in the border areas of a different maze, namely the open field (Schlager et al, 2011). Regarding the non-significant change found by Arteni et al (2010), it is possible that the existence of a railing on the open arms of EPM may have interfered with rats' behavior (Arteni et al, 2010).…”

Section: Effects Of Maternal Separation and Neonatal Hypoxia-ischemiamentioning

confidence: 99%

“…Increased locomotion estimated by the number of crossings or total distance may suggest that HI-treated animals spontaneously exhibit hyperactivity, a common adverse outcome of hypoxic-ischemic encephalopathy in humans (De Haan et al, 2006;Herrera-Marschitz et al, 2014;Volpe, 2008). According to existing evidence, increased locomotion has been found in adolescent, young adult or aged rats following neonatal HI or perinatal asphyxia paradigms (Fan et al, 2006;Lubics et al, 2005;McAuliffe et al, 2006;Rojas et al, 2013;Schlager et al, 2011;Venerosi et al, 2006). The horizontal ambulatory activity has been also used as a sign of exploration (Prut and Belzung, 2003).…”

Section: Effects Of Maternal Separation and Neonatal Hypoxia-ischemiamentioning

confidence: 99%

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Maternal separation prior to neonatal hypoxia‐ischemia: Impact on emotional aspects of behavior and markers of synaptic plasticity in hippocampus

Markostamou

Ioannidis

Dandi

et al. 2016

Intl J of Devlp Neuroscience

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 We examined the interaction between MS and ΝΗΙ on emotionality and markers of plasticity. Both MS and NHI increased anxiety levels, but only NHI induced depressionlike behavior. Maternal separation did not further increase emotionality in HI-treated rats. Both MS and NHI decreased synaptophysin levels in dentate gyrus and CA3 hippocampal areas. BDNF expression in CA3 was decreased only in the HI animals that were maternally-separated. AbstractExposure to early-life stress is associated with long-term alterations in brain and behavior, and may aggravate the outcome of neurological insults. This study aimed at investigating the possible interaction between maternal separation, a model of early stress, and subsequent neonatal hypoxia-ischemia on emotional behavior and markers of synaptic plasticity in hippocampus. Therefore, rat pups (N=60) were maternally separated for a prolonged (MS 180min) or a brief (MS 15min) period during the first six postnatal days, while a control group was left undisturbed. Hypoxia-ischemia was applied to a subgroup of each rearing condition on postnatal day 7. Emotional behavior was examined at three months of age and included assessments of anxiety (elevated plus maze), depression-like behavior (forced swimming) and spontaneous exploration (open field). Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in CA3 and dentate gyrus hippocampal regions. We found that neonatal hypoxia-ischemia caused increased levels of anxiety, depression-like behavior and locomotor activity (ambulation). Higher anxiety levels were also seen in maternally separated rats (MS180min) compared to non-maternally separated rats, but prolonged maternal separation prior to HI did not potentiate the HI-associated effect. No differences among the three rearing conditions were found regarding depression-like behavior or ambulation. Immunohistochemical evaluation of synaptophysin revealed that both prolonged maternal separation (MS180min) and neonatal hypoxia-ischemia significantly reduced its expression in the CA3 and dentate gyrus. Decreases in synaptophysin expression in these areas were not exacerbated in rats that were maternally separated for a prolonged period prior to HI. Regarding BDNF expression, we found a significant decrease in immunoreactivity only in the hypoxic-ischemic rats that were subjected to the prolonged maternal separation paradigm. The above findings suggest that early-life stress prior to neonatal hypoxia-ischemia leads to significant alterations in synaptic plasticity of the dorsal hippocampus during adulthood, but does not exacerbate HI-related changes in emotional behavior.

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“…We focused on Open-Field test (OF) [21] and tests assessing activity and anxiety, Novel-Object-Recognition test (NOR) [22] assessing memory function. Tests were performed as described previously [23] with some modifications. In short, animals were handled, every other day, during their active phase (i.e.…”

Section: Methodsmentioning

confidence: 99%

Effect of Propofol in the Immature Rat Brain on Short- and Long-Term Neurodevelopmental Outcome

et al. 2013

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BackgroundPropofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment.Methods6-day-old Wistar rats (P6), randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min) of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR) for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120.ResultsWestern blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT) in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3) in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point.ConclusionExposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals.

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Systemic G-CSF treatment does not improve long-term outcomes after neonatal hypoxic–ischaemic brain injury

Cited by 29 publications

References 62 publications

Ischemia/Reperfusion Injury Promotes and Granulocyte-Colony Stimulating Factor Inhibits Migration of Bone Marrow-Derived Stem Cells to Endometrium

Ischemia/Reperfusion Injury Promotes and Granulocyte-Colony Stimulating Factor Inhibits Migration of Bone Marrow-Derived Stem Cells to Endometrium

Maternal separation prior to neonatal hypoxia‐ischemia: Impact on emotional aspects of behavior and markers of synaptic plasticity in hippocampus

Effect of Propofol in the Immature Rat Brain on Short- and Long-Term Neurodevelopmental Outcome

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