Neurovascular Coupling in Rat Brain Operates Independent of Hemoglobin Deoxygenation (original) (raw)
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Hypoxemia, oxygen content, and the regulation of cerebral blood flow
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2016
This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2content (CaO2) rather than arterial O2tension (PaO2) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2sensor and upstream response effector, is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2. We surmise that 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2and thus maintain cerebral O2delivery; 2) evidence from studies implementing iso- and hypervolumic hemodilution, anemia, and polycythemia indicate that CaO2has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regul...
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2002
Hyperoxia reduces the hemodynamic latency and enhances the response magnitude of the evoked local cerebral blood Ž . Ž . flow LCBF . The objective of this study was to test the hypothesis that a change in the production of nitric oxide NO is involved in a unique change in evoked LCBF during hyperoxia. We measured LCBF in ␣-chloralose-anesthetized rats Ž . by laser-Doppler flowmetry. Systemic administration of the NO synthase inhibitor N -nitro-L-arginine LNA caused a Ž . Ž . decline in the baseline level of LCBF P-0.01 . The LNA intravenous injection during hyperoxia hyperoxia with LNA Ž . reduced the normalized evoked LCBF normalization with respect to the baseline level of LCBF in response to Ž . somatosensory stimulation by approximately 37% when compared under normal conditions normoxia without LNA Ž . Ž . P -0.01 , although that during normoxia normoxia with LNA did not cause a significant difference in the normalized evoked LCBF. The integrated neuronal activity under hyperoxia with LNA was approximately 11% lower than that Ž . under normoxia without LNA P-0.05 , although there was no significant difference in integrated neuronal activity between normoxia with LNA and normoxia without LNA. These results do not support our hypothesis and suggest the existence of another interaction mechanism involving oxygen for the enhancement of evoked LCBF under hyperoxia. ᮊ
Regulation of the Brain’s Vascular Responses to Oxygen
Circulation Research, 2002
The mechanism of oxygen-induced cerebral vasoconstriction has been sought for more than a century. Using genetically altered mice to enhance or disrupt extracellular superoxide dismutase (EC-SOD, SOD3), we tested the hypothesis that this enzyme plays a critical role in the physiological response to oxygen in the brain by regulating nitric oxide (NO · ) availability. Cerebral blood flow responses in these genetically altered mice to changes in P o 2 demonstrate that SOD3 regulates equilibrium between superoxide (·O 2 − ) and NO · , thereby controlling vascular tone and reactivity in the brain. That SOD3 opposes inactivation of NO · is shown by absence of vasoconstriction in response to P o 2 in the hyperbaric range in SOD3 +/+ mice, whereas NO-dependent relaxation is attenuated in SOD3 −/− mutants. Thus, EC-SOD promotes NO · vasodilation by scavenging ·O 2 − while hyperoxia opposes NO · and promotes constriction by enhancing endogenous ·O 2 − generation and decreasing basal vasodilat...
Cerebral hemodynamic response to acute hyperoxia in awake mice
Brain Research, 2014
Mouse Neural activation Two-photon laser scanning microscopy a b s t r a c t Cerebral hemodynamic response to acute hyperoxia was investigated in awake mice. Using laser-Doppler flowmetry (LDF), baseline cerebral blood flow (CBF) and the cerebrovascular responses to whisker stimulation were measured in awake mice during normoxia and hyperoxia. Using two-photon laser scanning microscopy (TPLSM), the changes in cortical microvasculature were measured during normoxia and hyperoxia. During hyperoxia (P a O 2 ¼482.3719.7 mmHg), baseline CBF was 6.8% lower than normoxia (P a O 2 ¼97.376.0 mmHg). The degree of increase in CBF evoked by whisker stimulation was greater during hyperoxia (18.175.0%) than normoxia (13.173.5%) (Po0.05). TPLSM imaging of the somatosensory cortex showed vasconstriction in arterioles and capillaries during hyperoxia. Since the effective diffusivity for oxygen in the capillary bed might decrease by hyperoxia due to a decrease in capillary blood volume according to Hyder's model, an increase in the cerebral metabolic rate of oxygen utilization by neural activation during hyperoxia might need a greater increase in CBF as compared with normoxia. The hemodynamic response to neural activation could be modified by acute hyperoxia due to modification of the relation between changes in CBF and oxygen consumption by neural activation.
Nitric oxide and cerebral blood flow responses to hyperbaric oxygen
Journal of Applied Physiology, 2000
We have tested the hypothesis that cerebral nitric oxide (NO) production is involved in hyperbaric O2 (HBO2) neurotoxicity. Regional cerebral blood flow (rCBF) and electroencephalogram (EEG) were measured in anesthetized rats during O2 exposure to 1, 3, 4, and 5 ATA with or without administration of the NO synthase inhibitor ( N ω-nitro-l-arginine methyl ester), l-arginine, NO donors, or the N-methyl-d-aspartate receptor inhibitor MK-801. After 30 min of O2 exposure at 3 and 4 ATA, rCBF decreased by 26–39% and by 37–43%, respectively, and was sustained for 75 min. At 5 ATA, rCBF decreased over 30 min in the substantia nigra by one-third but, thereafter, gradually returned to preexposure levels, preceding the onset of EEG spiking activity. Rats pretreated with N ω-nitro-l-arginine methyl ester and exposed to HBO2 at 5 ATA maintained a low rCBF. MK-801 did not alter the cerebrovascular responses to HBO2at 5 ATA but prevented the EEG spikes. NO donors increased rCBF in control rats but...
Cerebral blood flow and brain oxygenation in rats breathing oxygen under pressure
Journal of Cerebral Blood Flow & Metabolism, 2005
Hyperbaric oxygen (HBO 2 ) increases oxygen tension (PO 2 ) in blood but reduces blood flow by means of O 2 -induced vasoconstriction. Here we report the first quantitative evaluation of these opposing effects on tissue PO 2 in brain, using anesthetized rats exposed to HBO 2 at 2 to 6 atmospheres absolute (ATA). We assessed the contribution of regional cerebral blood flow (rCBF) to brain PO 2 as inspired PO 2 (PiO 2 ) exceeds 1 ATA. We measured rCBF and local PO 2 simultaneously in striatum using collocated platinum electrodes. Cerebral blood flow was computed from H 2 clearance curves in vivo and PO 2 from electrodes calibrated in vitro, before and after insertion. Arterial PCO 2 was controlled, and body temperature, blood pressure, and EEG were monitored. Scatter plots of rCBF versus PO 2 were nonlinear (R 2 ¼ 0.75) for rats breathing room air but nearly linear (R 2 ¼ 0.88-0.91) for O 2 at 2 to 6 ATA. The contribution of rCBF to brain PO 2 was estimated at constant inspired PO 2 , by increasing rCBF with acetazolamide (AZA) or decreasing it with N-nitro-L-arginine methyl ester (L-NAME). At basal rCBF (78 mL/100 g min), local PO 2 increased 7-to 33-fold at 2 to 6 ATA, compared with room air. A doubling of rCBF increased striatal PO 2 not quite two-fold in rats breathing room air but 13-to 64-fold in those breathing HBO 2 at 2 to 6 ATA. These findings support our hypothesis that HBO 2 increases PO 2 in brain in direct proportion to rCBF.
Brain Research Reviews, 2007
To determine the HbO 2 oxygenation level at the microcirculation, we used the hyperbaric chamber. The effects of hyperbaric oxygenation (HBO) were tested on vitality parameters in the brain at various pressures. Microcirculatory hemoglobin oxygen saturation (HbO 2 ), cerebral blood flow (CBF) and mitochondrial NADH redox state were assessed in the brain of awake restrained rats using a fiber optic probe. The hypothesis was that HBO may lead to maximal level in microcirculatory HbO 2 due to the amount of the dissolved O 2 to provide the O 2 consumed by the brain, and therefore no O 2 will be dissociated from the HbO 2 . Awake rats were exposed progressively to 15 min normobaric hyperoxia, 100% O 2 (NH) and to 90 min hyperbaric hyperoxia (HH) from 1.75 to 6.0 absolute atmospheres (ATA). NH and HH gradually decreased the blood volume measured by tissue reflectance and NADH but increased HbO 2 in relation to pO 2 in the chamber up to a nearly maximum effect at 2.5 ATA.
International Congress Series, 2002
A tight temporal and spatial relationship exists between neuronal activity, metabolism, and blood flow in the brain, and different temporal and spatial kinetics of oxygen consumption and blood flow lead to complex changes in regional cerebral haemoglobin oxygenation. Until now, it remains unclear whether neuronal activation leads to an early deoxygenation termed 'initial dip' preceding the rCBF response accompanied by hyperoxygenation. Although several studies have reported the 'initial dip', other studies did not confirm these findings, regardless of the species used. In an extensive series of experiments in anesthetized rats, we did not robustly find the dip using various modes of cortical O 2-measurements. Our findings for the first time demonstrate that the appearance of an initial dip and its amplitude may be correlated to the kinetics of the rCBF response. In addition, we show that the mode of analysis of spectroscopic data critically affects results. In our experiments, the finding of an initial dip was sensitive to the mode of spectroscopic analysis. Advanced models of spectroscopic analysis, including differential pathlength correction, should become standard in optical imaging spectroscopy studies. We conclude that in the rodent the initial dip is not a robust phenomenon, the occurrence of which may depend on the level of baseline CBF and thus mean transit time.
European Journal of Anaesthesiology, 2009
Background and objective Under physiological conditions, cerebral oxygen delivery is kept constant by adaptation of the regional cerebral blood flow (CBF) in relation to the oxygen content. So far, decreases of the regional CBF induced by a higher arterial oxygen content have been produced under hyperbaric or hyperviscous conditions. We tested whether local CBF is also reduced by a high haemoglobin (Hb) concentration at a normal haematocrit (Hct). Methods Compared with controls (n U 8), Hb content was increased to 19 g dl S1 in conscious rats by isovolaemic replacement of the plasma fraction with an artificially high Hb solution (Hb-based oxygen carriers; HH group, n U 8). In another group (n U 8), Hct was decreased by isovolaemic exchange with an Hb-based oxygen carrier resulting in a normal Hb content (NH group). Mean and regional CBF was measured by iodo-[ 14 C]-antipyrine autoradiography. Oxygen delivery was calculated from arterial oxygen content and CBF. Results Compared with the controls (Hb 15.3 g dl S1 , Hct 0.44), mean CBF was lower in the HH (Hb 20.3 g dl S1 , Hct 0.44) group by 23% (P <-0.05), but remained unchanged in the NH group (Hb 15.0 g dl S1 , Hct 0.29). On a local level, hyperoxygenation reduced CBF in 22 out of 39 brain regions. In the NH group mean CBF was unchanged, whereas local CBF was higher in 10 areas. In both groups, overall cerebral oxygen delivery was unchanged compared with the control group. Locally though, high arterial Hb content decreased oxygen delivery in one-third of the brain structures. Conclusion Whereas the overall cerebral oxygen delivery in the brain is maintained during hyperoxygenation and haemodilution, local oxygen delivery is decreased by high arterial Hb content in some brain regions. Eur J Anaesthesiol 26:245-252 Q 2009 European Society of Anaesthesiology.