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. · Jun 2012
Ischemic neuroprotection by TRPV1 receptor-induced hypothermia.
Although treatment of stroke patients with mild hypothermia is a promising therapeutic approach, chemicals inducing prompt and safe reduction of body temperature are an unmet need. We measured the effects of the transient receptor potential vanilloid-1 (TRPV1) agonist rinvanil on thermoregulation and ischemic brain injury in mice. ⋯ Both intraischemic and postischemic treatments provide permanent neuroprotection in animals subjected to transient middle cerebral artery occlusion (MCAo), an effect lost in mice artificially kept normothermic. Data indicate that TRPV1 receptor agonists are promising candidates for hypothermic treatment of stroke.
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J. Cereb. Blood Flow Metab. · Jun 2012
Use of spectral analysis with iterative filter for voxelwise determination of regional rates of cerebral protein synthesis with L-[1-11C]leucine PET.
A spectral analysis approach was used to estimate kinetic parameters of the L-[1-(11)C]leucine positron emission tomography (PET) method and regional rates of cerebral protein synthesis (rCPS) on a voxel-by-voxel basis. Spectral analysis applies to both heterogeneous and homogeneous tissues; it does not require prior assumptions concerning number of tissue compartments. Parameters estimated with spectral analysis can be strongly affected by noise, but numerical filters improve estimation performance. ⋯ Region-of-interest-SAIF and mean voxel-SAIF estimates of rCPS were highly correlated. Simulations showed that mean voxel-SAIF rCPS estimates were less biased and less variable than ROI-SAIF estimates in the whole brain and cortex; biases were similar in white matter. We conclude that estimation of rCPS with SAIF is improved when the method is applied at voxel level than in ROI analysis.
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J. Cereb. Blood Flow Metab. · Jun 2012
Neuroglobin regulates hypoxic response of neuronal cells through Hif-1α- and Nrf2-mediated mechanism.
Oxygen sensing in hypoxic neurons has been classically attributed to cytochrome c oxidase and prolyl-4-hydroxylases and involves stabilization of transcription factors, hypoxia-inducible factor-1α (Hif-1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) that mediate survival responses. On the contrary, release of cytochrome c into the cytosol during hypoxic stress triggers apoptosis in neuronal cells. We, here advocate that the redox state of neuroglobin (Ngb) could regulate both Hif-1α and Nrf2 stabilization and cytochrome c release during hypoxia. ⋯ Chronic hypoxia, however, resulted in oxidation and degradation of Ngb, accumulation of ferric ions and release of cytochrome c that triggered apoptosis. Administration of N-acetyl-cysteine during hypoxic conditions improved neuronal survival by preventing Ngb oxidation and degradation. Taken together, these results establish a role for Ngb in regulating both the survival and apoptotic mechanisms associated with hypoxia.
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J. Cereb. Blood Flow Metab. · May 2012
Nitrative stress in cerebral endothelium is mediated by mGluR5 in hyperhomocysteinemia.
Hyperhomocysteinemia (HHcy) disrupts nitric oxide (NO) signaling and increases nitrative stress in cerebral microvascular endothelial cells (CMVECs). This is mediated, in part, by protein nitrotyrosinylation (3-nitrotyrosine; 3-NT) though the mechanisms by which extracellular homocysteine (Hcy) generates intracellular 3-NT are unknown. Using a murine model of mild HHcy (cbs(+/-) mouse), we show that 3-NT is significantly elevated in cerebral microvessels with concomitant reductions in serum NO bioavailability as compared with wild-type littermate controls (cbs(+/+)). ⋯ Activation of mGluR5 is both sufficient and necessary to drive the nitrative stress because direct activation using the mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine also increased iNOS expression and 3-NT formation while knockdown of mGluR5 receptor expression by short hairpin RNA (shRNA) blocked their increase in response to Hcy. Nitric oxide derived from iNOS was required for Hcy-mediated formation of 3-NT because the effect was blocked by 1400W. These results provide the first evidence for a receptor-dependent process that explains how plasma Hcy levels control intracellular nitrative stress in cerebral microvascular endothelium.
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J. Cereb. Blood Flow Metab. · Mar 2012
Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain.
Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO(2)) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BF(ix)) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. ⋯ SO(2) correlates with chronological age (r=-0.54, P value ≤0.001) but not with PMA (r=-0.07), whereas BF(ix) and rCMRO(2) correlate better with PMA (r=0.37 and 0.43, respectively, P value ≤0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO(2) are more accurate biomarkers of the brain development than SO(2) in the premature newborns.