PubMed Health⌕ Search

Biomedical subjects

Laura Bennet

Publications and source records attributed to Laura Bennet.

24 records · Page 2Linked to original sources
PubMed2004

Window of opportunity of cerebral hypothermia for postischemic white matter injury in the near-term fetal sheep.

Postresuscitation cerebral hypothermia is consistently neuroprotective in experimental preparations; however, its effects on white matter injury are poorly understood. Using a model of reversible cerebral ischemia in unanesthetized near-term fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.4 +/- 0.1 degrees C to between 30 and 33 degrees C), induced at different times after reperfusion and continued for 72 hours after ischemia, on injury in the parasagittal white matter 5 days after ischemia. Cooling started within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intragyral white matter compared with sham cooling (41 +/- 20 vs 18 +/- 11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14 +/- 12 vs 91 +/- 51, P < 0.05). Reactive microglia were profoundly suppressed compared with sham cooling (4 +/- 6 vs 38 +/- 18 per field, P < 0.05) with no effect on numbers of astrocytes. When cooling was delayed until 5.5 hours after reperfusion there was no significant effect on loss of oligodendrocytes (24 +/- 12 per field). In conclusion, hypothermia can effectively protect white matter after ischemia, but only if initiated early after the insult. Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia.

Animals↗
PubMed2003

Key neuroprotective role for endogenous adenosine A1 receptor activation during asphyxia in the fetal sheep.

BACKGROUND AND PURPOSE: The fetus is well known to be able to survive prolonged exposure to asphyxia with minimal injury compared with older animals. We and others have observed a rapid suppression of EEG intensity with the onset of asphyxia, suggesting active inhibition that may be a major neuroprotective adaptation to asphyxia. Adenosine is a key regulator of cerebral metabolism in the fetus. METHODS: We therefore tested the hypothesis that infusion of the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), given before 10 minutes of profound asphyxia in near-term fetal sheep, would prevent neural inhibition and lead to increased brain damage. RESULTS: DPCPX treatment was associated with a transient rise and delayed fall in EEG activity in response to cord occlusion (n=8) in contrast with a rapid and sustained suppression of EEG activity in controls (n=8). DPCPX was also associated with an earlier and greater increase in cortical impedance, reflecting earlier onset of primary cytotoxic edema, and a significantly smaller reduction in calculated cortical heat production after the start of cord occlusion. After reperfusion, DPCPX-treated fetuses but not controls developed delayed onset of seizures, which continued for 24 hours, and sustained greater selective hippocampal, striatal, and parasagittal neuronal loss after 72-hour recovery. CONCLUSIONS: These data support the hypothesis that endogenous activation of the adenosine A1 receptor during severe asphyxia mediates the initial suppression of neural activity and is an important mechanism that protects the fetal brain.

Animals↗
PubMed2003

Insulin-like growth factor (IGF)-1 suppresses oligodendrocyte caspase-3 activation and increases glial proliferation after ischemia in near-term fetal sheep.

Insulin-like growth factor (IGF-1) markedly increases myelination and glial numbers in white matter after ischemia in near-term fetal sheep; however, it is unclear whether this is due to reduced cell loss or increased secondary proliferation. Brain injury was induced in near-term fetal sheep by 30 minutes of bilateral carotid artery occlusion. Ninety minutes after the occlusion, fetuses were given, intracerebroventricularly, either a single dose of IGF-1 (either 3 or 30 micro g), or 3 micro g followed by 3 micro g over 24 hours (3 + 3 micro g). White matter was assessed 4 days after reperfusion. Three micrograms, but not 30 micro g of IGF-1 prevented loss of oligodendrocytes and myelin basic protein density (P < 0.001) compared to the vehicle-treated ischemia controls. No additional effect was observed in the 3 + 3 micro g group. IGF-1 treatment was associated with reduced caspase-3 activation and increased glial proliferation in a similar dose-dependent manner. Caspase-3 was only expressed in oligodendrocytes that showed apoptotic morphology. Proliferating cell nuclear antigen co-localized with both oligodendrocytes and astrocytes and microglia. Thus, increased oligodendrocyte numbers after IGF-1 treatment is partly due to suppression of apoptosis, and partly to increased proliferation. In contrast, the increase in reactive glia was related only to proliferation. Speculatively, reactive glia may partly mediate IGF-1 white matter protection.

Animals↗
PubMed2002

Meconium and fetal hypoxia: some experimental observations and clinical relevance.

In an experimental study, chemically sympathectomised near term fetal sheep and a control group were subjected to repeated episodes of acute hypoxia. Despite severe hypotension and metabolic acidosis, no animal in the control group had meconium-stained amniotic fluid, whereas every animal in the sympathectomised group had heavily meconium-stained amniotic fluid at the end of the experiments. These data and the available literature do not support a direct association between acute hypoxia and meconium-stained amniotic fluid but suggest that a reduction in sympathetic neural tone must be a component of meconium passage. Clinical and experimental data on the occurrence of meconium-stained amniotic fluid are reviewed.

Amniotic Fluid↗