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. · Oct 2012
Randomized Controlled Trial Multicenter Study Clinical TrialSerum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy.
Inflammatory cytokines may mediate hypoxic-ischemic (HI) injury and offer insights into the severity of injury and the timing of recovery. In our randomized, multicenter trial of hypothermia, we analyzed the temporal relationship of serum cytokine levels in neonates with hypoxic-ischemic encephalopathy (HIE) with neurodevelopmental outcome at 12 months. Serum cytokines were measured every 12 hours for 4 days in 28 hypothermic (H) and 22 normothermic (N) neonates with HIE. ⋯ However, IL-6, IL-8, and MCP-1 showed a biphasic pattern in the H group, with early and delayed peaks. In H neonates with better outcomes, uniform down modulation of IL-6, IL-8, and IL-10 from their peak levels at 24 hours to their nadir at 36 hours was observed. Modulation of serum cytokines after HI injury may be another mechanism of improved outcomes in neonates treated with induced hypothermia.
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J. Cereb. Blood Flow Metab. · Oct 2012
Effects of therapeutic hypothermia on inflammasome signaling after traumatic brain injury.
Traumatic brain injury (TBI) activates the NALP1/NLRP1 inflammasome, which is an important component of the early innate inflammatory response to injury. We investigated the influence of therapeutic hypothermia on inflammasome activation after TBI. Adult male Sprague-Dawley rats were subjected to moderate fluid percussion brain injury. ⋯ Cultured cortical neurons subjected to stretch injury demonstrated significant secretion of caspase-1 into the culture medium and caspase-3 activation, both results reduced by hypothermic treatment. Posttraumatic hypothermia decreases inflammasome signaling in neurons and reduces the innate immune response to TBI at 24 hours after injury. Therapeutic hypothermia may protect the injured central nervous system by targeting the detrimental consequences of the innate immune response to injury.
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J. Cereb. Blood Flow Metab. · Sep 2012
Reproducibility of cerebral blood flow assessment using a quantitative SPECT reconstruction program and split-dose 123I-iodoamphetamine in institutions with different γ-cameras and collimators.
Single photon emission computed tomography (SPECT) is used widely in clinical studies. However, the technique requires image reconstruction and the methods for correcting scattered radiation and absorption are not standardized among SPECT procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be constant across SPECT models. ⋯ The consistency of the CBFs of the patients measured at the two facilities were good in all cases. Our results show that CBF measured by QSPECT/DTARG in the same patients is reproducible in different SPECT models. This indicates that standardized evaluation of CBF can be performed in large multicenter studies.
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J. Cereb. Blood Flow Metab. · Sep 2012
ReviewSulfonylurea receptor 1 in central nervous system injury: a focused review.
The sulfonylurea receptor 1 (Sur1)-regulated NC(Ca-ATP) channel is a nonselective cation channel that is regulated by intracellular calcium and adenosine triphosphate. The channel is not constitutively expressed, but is transcriptionally upregulated de novo in all cells of the neurovascular unit, in many forms of central nervous system (CNS) injury, including cerebral ischemia, traumatic brain injury (TBI), spinal cord injury (SCI), and subarachnoid hemorrhage (SAH). The channel is linked to microvascular dysfunction that manifests as edema formation and delayed secondary hemorrhage. ⋯ In models of stroke and TBI, glibenclamide ameliorates edema, secondary hemorrhage, and tissue damage. In a model of SAH, glibenclamide attenuates the inflammatory response due to extravasated blood. Clinical trials of an intravenous formulation of glibenclamide in TBI and stroke underscore the importance of recent advances in understanding the role of the Sur1-regulated NC(Ca-ATP) channel in acute ischemic, traumatic, and inflammatory injury to the CNS.
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Inflammation is a highly dynamic and complex adaptive process to preserve and restore tissue homeostasis. Originally viewed as an immune-privileged organ, the central nervous system (CNS) is now recognized to have a constant interplay with the innate and the adaptive immune systems, where resident microglia and infiltrating immune cells from the periphery have important roles. ⋯ Molecular imaging is the method of choice to try to decipher key aspects of the dynamic interplay of various inducers, sensors, transducers, and effectors of the orchestrated inflammatory response in vivo in animal models and patients. Here, we review the basic principles of NI with emphasis on microglia and common neurologic disease mechanisms, the molecular targets which are being used and explored for imaging, and molecular imaging of NI in frequent neurologic diseases, such as stroke, MS, neurodegeneration, epilepsy, encephalitis, and gliomas.