Postnatal development of the cerebral blood flow velocity response to changes in CO<sub>2</sub> and mean arterial blood pressure in the piglet

Haaland, Kirsti; Karlsson, Bente R.; Skovlund, Eva; Lagercrantz, Hugo; Thoresen, Marianne

doi:10.1111/j.1651-2227.1995.tb13579.x

Cited by 18 publications

(19 citation statements)

References 27 publications

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“…These developmental changes in BOLD CVR are in contrast to a previous microsphere study that failed to observe differences in the CBF response to CO 2 between young (1-2 wk) and adult (6 -10 mo) pigs (32). Our results also differ from another microsphere study that suggested that CO 2 reactivity is depressed for the first week of life, but quickly reaches adult levels between 1 wk old and 1 mo old (33). A major distinction between the current study and the cited studies is the CBF measurement approach.…”

Section: Discussioncontrasting

confidence: 56%

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

et al. 2011

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ABSTRACT:The swine brain is emerging as a potentially valuable translational animal model of neurodevelopment and offers the ability to assess the impact of experimentally induced neurological disorders. The goal for this study was to characterize swine brain development using noninvasive MRI measures of microstructural and cerebrovascular changes. Thirteen pigs at various postnatal ages (2.3-43.5 kg) were imaged on a 1.5-Tesla MRI system. Microstructural changes were assessed using diffusion tensor imaging measures of mean diffusivity and fractional anisotropy. Cerebrovascular changes were assessed using arterial spin labeling measures of baseline cerebral blood flow (CBF) and the cerebrovascular reactivity (CVR) of the blood-oxygen level dependent (BOLD) MRI signal to CO 2 . We found a positive logarithmic relationship for regional tissue volumes and fractional anisotropy with body weight, which is similar to the pattern reported in the developing human brain. Unlike in the maturing human brain, no consistent changes in mean diffusivity or baseline CBF with development were observed. Changes in BOLD CVR exhibited a positive logarithmic relationship with body weight, which may impact the interpretation of functional MRI results at different stages of development. This animal model can be validated by applying the same noninvasive measures in humans. (Pediatr Res 69: 418-424, 2011) P rocesses of human brain development are integral to the understanding of the long-term impact of neurological disorders afflicting the immature brain. Animal models provide a means to investigate developmental processes in a controlled manner and to model the effects of disease and injury on the immature brain. Dobbing and Sands (1) proposed that the swine brain may represent an appropriate model for the immature human brain based on the timing of the brain growth spurt (rapid stages of brain growth), which is recognized as a period of increased vulnerability to injury. Additional benefits of the swine model for developmental neuroscience include similar histology, cortical folding, and gray-matter (GM)-to-white-matter (WM) ratio to humans (1). Moreover, recent advances in transgenic neural gene manipulations and the ability to model brain injury and neurologic disorders have also supported the increasing use of swine as a model for neuroscience and neurosurgical research (2,3).Ontogeny of the brain typically focuses on structural changes during development; however, these changes may also be linked to cerebrovascular development based on the observed association between rapid stages of brain growth and increased cerebral perfusion that is believed to be required to match increased metabolic needs (4). Given that many pathologies of the immature brain involve compromised cerebral perfusion (e.g., neonatal encephalopathy and intraventricular hemorrhage), there is a need to characterize both cerebrovascular and structural changes occurring in animal models of early human brain development.MRI is emerging as the prominent modality for ...

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Section: Discussioncontrasting

confidence: 56%

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

et al. 2011

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“…In a different model, piglets that were younger than 4 d had a low CO 2 reactivity and did not fully autoregulate in response to MABP changes during the first days of life. At 4 d of age, adult responses have developed in the piglets (53). This may explain the lack of significant differences between the CO 2 groups in our study based on piglets Ͻ36 h of age.…”

Section: Discussioncontrasting

confidence: 36%

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Munkeby

Børke

Björnland³

et al. 2004

Pediatr Res

121

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Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O 2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O 2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O 2 compared with 21% O 2 . Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p ϭ 0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O 2 (p ϭ 0.003) and 100% O 2 (p ϭ 0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O 2 as compared with 21% O 2 (p Ͻ 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O 2 were considerably reduced compared with both baseline (p ϭ 0.001) and piglets that were resuscitated with 21% O 2 (p ϭ 0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Traditionally, asphyxiated newborn infants have been resuscitated using 100% oxygen in the delivery room (1). However, clinical trials have shown that room air is as efficient as pure oxygen in securing the survival of asphyxiated newborn infants (2-5). Therefore there is an ongoing debate whether to use ambient air or 100% O 2 in neonatal resuscitation (6 -9).Hyperoxia followed by reoxygenation is thought to increase the production of reactive oxygen species and disrupt the antioxidant mechanisms (10). Elevated oxidative stress can directly influence the cell cycle and additionally alter a number of significant cell functions, such as signal transduction, DNA and RNA synthesis, protein synthesis, and enzyme activation (11,12). Furthermore, hypoxic-ischemic injury and reactive oxygen species are found to trigger inflammation in the immature brain (13).Interstitial glycerol is a sensitive and reliable marker of cell damage in experimental cerebral ischemia (14 -16). Degradation of membrane phospholipids is a well-known phenomenon in acute brain injuries and is thought to underlie the disturbance of vital cellular membrane functions.Matrix metalloproteinases (MMPs) are a family of Ͼ20 zinc-and calcium-dependent endopeptidases that are involved in the remodeling of the extracellular matrix (ECM) in a variety of physiologic and pathologic conditions (17

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“…strong in newborn dogs [21]; the reactivity, however, was 19%/kPa change in CO 2 when expressed relative to the level of normocapnic CBF, which is not so different from the normal, adult value of 30%/ kPa. Rather low CBF-CO 2 reactivity has also been reported in rat [22] and dog pups [23], and in piglets [24] shortly after birth. We found a reduced CBF-CO 2 reactivity on the first day of life in mechanically ventilated infants [25].…”

Section: Effect On Cbfmentioning

confidence: 99%

Is Periventricular Leucomalacia aResult of Hypoxic-Ischaemic Injury?

Greisen

Vannucci²

2001

Neonatology

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Decrease in the arterial partial pressure of carbon dioxide (PaCO₂) causes a reduction in cerebral blood flow in humans and in most animal species; in adults as well as in newborns and even in fetal life. Severely decreased PaCO₂ increases cerebral lactate production, modifies spontaneous electric brain activity, and may decrease the metabolic rate of oxygen. A relation between very low PaCO₂ and brain injury, however, has not been shown in adult humans or full-term newborn infants, nor in perinatal animals. In contrast, an association between low PaCO₂ and cerebral palsy and white matter injury in preterm infants has been reported repeatedly. A cause-and-effect relation is suggested by data from the immature rat: brain damage induced by ligation of a carotid artery can be reduced by adding CO₂ to the inspired gas and hence avoiding the consequences of spontaneous hyperventilation. This may be relevant for the clinical care of preterm infants, since PaCO₂ to a large extent is a function of respiratory management. The questions to be addressed are whether hypocapnia sensitises the brain to hypoxaemia, and also whether the escape mechanisms are less effective in the preterm human brain.

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Postnatal development of the cerebral blood flow velocity response to changes in CO₂ and mean arterial blood pressure in the piglet

Cited by 18 publications

References 27 publications

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Is Periventricular Leucomalacia aResult of Hypoxic-Ischaemic Injury?

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Postnatal development of the cerebral blood flow velocity response to changes in CO2 and mean arterial blood pressure in the piglet

Cited by 18 publications

References 27 publications

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Is Periventricular Leucomalacia aResult of Hypoxic-Ischaemic Injury?

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Postnatal development of the cerebral blood flow velocity response to changes in CO₂ and mean arterial blood pressure in the piglet