Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Jan 2010
Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia.
Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [(18)F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. ⋯ Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [(18)F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.
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J. Cereb. Blood Flow Metab. · Jan 2010
Minocycline reduces neuronal death and attenuates microglial response after pediatric asphyxial cardiac arrest.
The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest (ACA) in the developing brain are unknown. This study aimed at investigating the possible role of microglial activation in neuronal death in developing brain after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by resuscitation. ⋯ Minocycline attenuated ACA-induced increases in MIP-1alpha and RANTES (P<0.05). These data show that microglial activation and cytokine production are increased in immature brain after ACA. The beneficial effect of minocycline suggests an important role for microglia in selective neuronal death after pediatric ACA, and a possible therapeutic target.
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J. Cereb. Blood Flow Metab. · Dec 2009
Involvement of the PTEN-AKT-FOXO3a pathway in neuronal apoptosis in developing rat brain after hypoxia-ischemia.
The proapoptotic function of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphatase has been linked to its capacity to antagonize the phosphatidylinositol-3-kinase-Akt signaling pathway. Previous studies have shown that the Forkhead transcriptional factor (FOXO3a) is a critical effector of the PTEN-mediated tumor suppressor. However, whether the PTEN-Akt-FOXO3a pathway is involved in neuronal apoptosis in developing rat brain after hypoxia-ischemia (HI) is unclear. ⋯ Moreover, the downregulation of Bim caused by PTEN inhibition attenuated cellular apoptosis in developing rat brain. Our findings suggest that the PTEN-Akt-FOXO3a pathway is involved in neuronal apoptosis in neonatal rat brain after HI. Agents targeting PTEN may offer a promise to rescue neurons from HI brain damage.
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J. Cereb. Blood Flow Metab. · Nov 2009
Cerebral blood flow, blood volume, and oxygen metabolism dynamics in human visual and motor cortex as measured by whole-brain multi-modal magnetic resonance imaging.
The development of neuroimaging methods to characterize flow-metabolism coupling is crucial for understanding mechanisms that subserve oxygen delivery. Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) contrast reflects composite changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral metabolic rate of oxygen consumption (CMRO(2)). However, it is difficult to separate these parameters from the composite BOLD signal, thereby hampering MR-based flow-metabolism coupling studies. ⋯ This approach allows for CBV, CBF, and CMRO(2) to be estimated, yielding (mean+/-s.d.): DeltaCBF=63%+/-12%, DeltaCBV=17%+/-7%, and DeltaCMRO(2)=13%+/-11% in the visual cortex, and DeltaCBF=46%+/-11%, DeltaCBV=8%+/-3%, and DeltaCMRO(2)=12%+/-13% in the motor cortex. Following the visual and motor tasks, the BOLD signal became more negative (P=0.003) and persisted longer (P=0.006) in the visual cortex compared with the motor cortex, whereas CBV and CBF returned to baseline earlier and equivalently. The proposed whole-brain technique should be useful for assessing regional discrepancies in hemodynamic reactivity without the use of intravascular contrast agents.
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J. Cereb. Blood Flow Metab. · Oct 2009
Increased cerebral blood volume and oxygen consumption in neonatal brain injury.
With the increasing interest in treatments for neonatal brain injury, bedside methods for detecting and assessing injury status and evolution are needed. We aimed to determine whether cerebral tissue oxygenation (StO(2)), cerebral blood volume (CBV), and estimates of relative cerebral oxygen consumption (rCMRO(2)) determined by bedside frequency-domain near-infrared spectroscopy (FD-NIRS) have the potential to distinguish neonates with brain injury from those with non-brain issues and healthy controls. We recruited 43 neonates < or =15 days old and >33 weeks gestational age (GA): 14 with imaging evidence of brain injury, 29 without suspicion of brain injury (4 unstable, 6 stable, and 19 healthy). ⋯ StO(2) was significantly higher in brain injured compared with unstable neonates, but not statistically different from stable or healthy neonates. Brain-injured neonates were distinguished from all others by significant increases in CBV and rCMRO(2). In conclusion, although NIRS measures of StO(2) alone may be insensitive to evolving brain injury, increased CBV and rCMRO(2) seem to be useful for detecting neonatal brain injury and suggest increased neuronal activity and metabolism occurs acutely in evolving brain injury.