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. · Dec 2013
Neuroprotective effects of geranylgeranylacetone in experimental traumatic brain injury.
Geranylgeranylacetone (GGA) is an inducer of heat-shock protein 70 (HSP70) that has been used clinically for many years as an antiulcer treatment. It is centrally active after oral administration and is neuroprotective in experimental brain ischemia/stroke models. We examined the effects of single oral GGA before treatment (800 mg/kg, 48 hours before trauma) or after treatment (800 mg/kg, 3 hours after trauma) on long-term functional recovery and histologic outcomes after moderate-level controlled cortical impact, an experimental traumatic brain injury (TBI) model in mice. ⋯ Furthermore, GGA pretreatment reduced the lesion size and neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex when compared with vehicle-treated TBI controls. Notably, GGA was also effective in a posttreatment paradigm, showing significant improvements in sensorimotor function, and reducing cortical neuronal loss. Given these neuroprotective actions and considering its longstanding clinical use, GGA should be considered for the clinical treatment of TBI.
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J. Cereb. Blood Flow Metab. · Nov 2013
Observational StudyCerebral extracellular lactate increase is predominantly nonischemic in patients with severe traumatic brain injury.
Growing evidence suggests that endogenous lactate is an important substrate for neurons. This study aimed to examine cerebral lactate metabolism and its relationship with brain perfusion in patients with severe traumatic brain injury (TBI). A prospective cohort of 24 patients with severe TBI monitored with cerebral microdialysis (CMD) and brain tissue oxygen tension (PbtO2) was studied. ⋯ Samples with elevated CMD lactate were frequently observed (41±8%), and we found that brain lactate elevations were predominantly associated with glycolysis and normal PbtO2 (73±8%) rather than brain hypoxia (14±6%). Furthermore, glycolytic lactate was always associated with normal or hyperemic brain perfusion, whereas all episodes with hypoxic lactate were associated with diffuse oligemia. Our findings suggest predominant nonischemic cerebral extracellular lactate release after TBI and support the concept that lactate may be used as an energy substrate by the injured human brain.
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J. Cereb. Blood Flow Metab. · Nov 2013
Cerebral blood flow quantification using vessel-encoded arterial spin labeling.
Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. ⋯ Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.
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J. Cereb. Blood Flow Metab. · Nov 2013
Tissue-type plasminogen activator mediates neuronal detection and adaptation to metabolic stress.
Adenosine monophosphate-activated protein kinase (AMPK) is an energy sensor that regulates cellular adaptation to metabolic stress. Tissue-type plasminogen activator (tPA) is a serine proteinase found in the intravascular space, where its main role is as thrombolytic enzyme, and in neurons, where its function is less well understood. Here, we report that glucose deprivation induces the mobilization and package of neuronal tPA into presynaptic vesicles. ⋯ This effect is independent of tPA's proteolytic properties, and instead requires the presence of functional N-methyl-D-aspartate receptors (NMDARs). In agreement with these observations, positron emission tomography (PET) studies and biochemical analysis with synaptoneurosomes indicate that the intravenous administration of recombinant tPA (rtPA) after transient middle cerebral artery occlusion (tMCAO) induces AMPK activation in the synaptic space and NMDAR-mediated glucose uptake in the ischemic brain. These data indicate that the release of neuronal tPA or treatment with rtPA activate a cell signaling pathway in the synaptic space that promotes the detection and adaptation to metabolic stress.
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J. Cereb. Blood Flow Metab. · Nov 2013
Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model.
Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. ⋯ Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.