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. · Apr 2007
Imaging of brain hypoxia in permanent and temporary middle cerebral artery occlusion in the rat using 18F-fluoromisonidazole and positron emission tomography: a pilot study.
In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. Previous human studies using 18F-fluoromisonidazole and positron emission tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue hypoxia, which had normalized at repeat scan >48 h later. In the only validation study of 18F-FMISO, using ex vivo autoradiography in thread middle cerebral artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h after reperfusion, raising questions about the use of 18F-FMISO as a hypoxia tracer. ⋯ In contrast, there was no demonstrable tracer retention in either temporary MCAo models, and histopathology showed ischemic changes only. These results document elevated 18F-FMISO uptake in the stroke area only in the early phase of MCAo, but not after early reperfusion nor when tissue necrosis has developed. These findings strongly support the validity of 18F-FMISO as a marker of viable hypoxic tissue/penumbra after stroke.
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J. Cereb. Blood Flow Metab. · Apr 2007
Feasibility of velocity selective arterial spin labeling in functional MRI.
Arterial spin labeling (ASL) magnetically inverts or saturates the spins in arterial blood and uses them as endogenous tracers. Conventionally, the tagging band is upstream or nonselective to the target slices. In the brain, ASL-based functional magnetic resonance imaging (fMRI) has been shown to detect activation better localized in gray matter than blood oxygenation level dependent contrast. ⋯ Velocity selective-arterial spin labeling can further distinguish the contribution from different flow directions but spurious elevation of fractional signal change may occur when the VS tagging is applied off the direction of blood supply. The flow reaches the vicinity of perfusion at a cutoff velocity (Vc) of 2 cm/sec whereas the activation exclusively detected by Vc=4 cm/sec implies the arteriolar response to the neuronal activity and a respondent vessel diameter up to 240 microm. Velocity selective imaging can remove intravascular signal from the vessels where the flow velocity is above Vc.
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J. Cereb. Blood Flow Metab. · Mar 2007
Bad as a converging signaling molecule between survival PI3-K/Akt and death JNK in neurons after transient focal cerebral ischemia in rats.
Bad, a proapoptotic Bcl-2 family protein, plays a critical role in determining cell death/survival. The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and the c-Jun N-terminal kinase (JNK) pathway are thought to be involved in regulation of Bad. Therefore, the present study was performed to clarify the role of Bad as a common target of the PI3-K/Akt and JNK pathways after transient focal cerebral ischemia (tFCI) in rats. ⋯ The present study indicates that signal predominance varies from PI3-K/Akt-mediated survival signaling to JNK-mediated death signaling with the development of neuronal damage in the peripheral area after tFCI. This study also suggests that PI3-K/Akt has a role in Bad inactivation, whereas the JNK pathway is involved in Bad activation. We conclude that Bad may be an integrated checkpoint of PI3-K/Akt-mediated survival signaling and JNK-mediated death signaling and that it contributes to cell fate in the peripheral area after cerebral ischemia.
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J. Cereb. Blood Flow Metab. · Mar 2007
Nonlinear neurovascular coupling in rat sensory cortex by activation of transcallosal fibers.
Functional neuroimaging and normal brain function rely on the robust coupling between neural activity and cerebral blood flow (CBF), that is neurovascular coupling. We examined neurovascular coupling in rat sensory cortex in response to direct stimulation of transcallosal pathways, which allows examination of brain regions inaccessible to peripheral stimulation techniques. Using laser-Doppler flowmetry to record CBF and electrophysiologic recordings of local field potentials (LFPs), we show an exponential relation between CBF responses and summed LFP amplitudes. ⋯ The data suggest that preserved activity of both AMPA and NMDA receptors is necessary for the full CBF response evoked by stimulation of rodent interhemispheric connections. AMPA receptor activation gives rise to a measurable LFP, but NMDA receptor activation does not. The lack of a measurable LFP from neural processes that contribute importantly to CBF may explain some of the difficulties in transforming extracellular current or voltage measurements to a hemodynamic response.
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J. Cereb. Blood Flow Metab. · Feb 2007
White matter injury correlates with hypertonia in an animal model of cerebral palsy.
Hypertonia and postural deficits are observed in cerebral palsy and similar abnormalities are observed in postnatal rabbits after antenatal hypoxia-ischemia. To explain why some kits become hypertonic, we hypothesized that white matter injury was responsible for the hypertonia. We compared newborn kits at postnatal day 1 (P1) with and without hypertonia after in vivo global fetal hypoxia-ischemia in pregnant rabbits at 70% gestation. ⋯ Thus, hypertonia is associated with white matter injury, and a population of hypertonia can be identified by magnetic resonance imaging variables. The white matter injury manifests as a decrease in the number and density of fiber tracts causing the decrease in FA and volume. Furthermore, the dynamic response of FA may be a good indicator of the plasticity and repair of the postnatal developing brain.