Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy

This study aimed to examine the cortical microvessel diameter response to hypercapnia in misery perfusion using two-photon laser scanning microscopy (TPLSM). We evaluated whether the vascular response to hypercapnia could represent the cerebrovascular reserve. Cerebral blood flow (CBF) during normocapnia and hypercapnia was measured by laser-Doppler flowmetry through cranial windows in awake C57/BL6 mice before and at 1, 7, 14, and 28 days after unilateral common carotid artery occlusion (UCCAO). Diameters of the cortical microvessels during normocapnia and hypercapnia were also measured by TPLSM. Cerebral blood flow and the vascular response to hypercapnia were decreased after UCCAO. Before UCCAO, vasodilation during hypercapnia was found primarily in arterioles (22.9%±3.5%). At 14 days after UCCAO, arterioles, capillaries, and venules were autoregulatorily dilated by 79.5%±19.7%, 57.2%±32.3%, and 32.0%±10.8%, respectively. At the same time, the diameter response to hypercapnia in arterioles was significantly decreased to 1.9%±1.5%. A significant negative correlation was observed between autoregulatory vasodilation and the diameter response to hypercapnia in arterioles. Our findings indicate that arterioles play main roles in both autoregulatory vasodilation and hypercapnic vasodilation, and that the vascular response to hypercapnia can be used to estimate the cerebrovascular reserve.     

Cerebral blood flow regulation in neonatal rabbits is altered by chronic cocaine administration

Maternal cocaine abuse has several deleterious effects in the newborn, including perinatal asphyxia, hypoxia, and hypercapnia. We hypothesized that chronic cocaine exposure during development may alter cerebral blood flow (CBF) regulation. We studied 16 neonatal rabbits that had received cocaine (20 mg/kg, i.p. b.i.d.) or saline since birth. Changes in CBF were measured by laser doppler flowmetry before (baseline), and during hypercapnia (FiCO₂=7.5%), hypoxia (FiO₂=12%), and asphyxia (apnea for 1 min). During hypercapnia, CBF increased less in cocaine than in control animals (28±3% vs. 69±10%, P<0.05). During hypoxia, CBF increased similarly in both groups. During reventilation after asphyxia, CBF increased more in cocaine than in control animals (391±52% vs. 225±43%, P<0.05). Chronic cocaine exposure during brain development appears to alter CBF regulation to hypercapnia and asphyxia, which may put the drug exposed newborn at risk for neurologic injury around birth.     

Laser-doppler flowmetry

Laser-Doppler flowmetry is a new technique for noninvasive and continuous measurement of local microcirculatory cerebral and spinal-cord blood flow. The flow estimate by this technique is based on the assessment of the Doppler shift of low-power laser light, which is scattered by moving red blood cells. Laser-Doppler flowmetry has been validated for various organs, including the central nervous system. These studies revealed a linear relationship between relative changes of the Doppler signal and blood flow over a wide range of pharmacological as well as pathological flow alterations, including cerebral ischemia. The usefulness of laser-Doppler flowmetry in experimental as well as clinical applications has received growing attention. The superiority of the technique lies in its high spatial and temporal resolution. Disadvantages are the difficulty of obtaining absolute flow values and the sensitivity to artifacts. The versatility and on-line capacity of laser-Doppler flowmetry might allow new insights into the pathophysiology of alterations of the cerebral and spinal-cord microcirculation.     

Regional cerebral blood flow during hypercapnia in the anesthetized rabbit

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.     

The effects of graded hypercapnia on the activation flow coupling response due to forepaw stimulation in alpha-chloralose anesthetized rats

Activation flow coupling (AFC), changes in cerebral blood flow (CBF) due to changes in neural activity with functional stimulation, provides the physiological basis of many neuroimaging techniques. Hypercapnia leads to an increase in CBF while neural activity remains unaffected. Laser Doppler (LD) flowmetry was used to measure CBF changes (LD(CBF)) in the somatosensory cortex due to periodic electrical forepaw stimulation (4 s in duration) before and during graded hypercapnia (3% CO(2), 5% CO(2) and 10% CO(2)). With increasing CO(2) concentrations, the baseline LD(CBF) progressively increased. The peak height (PH) of the LD(CBF) response, expressed as a percent change from the observed baseline for each hypercapnic state, significantly decreased (P<0.05) with increasing CO(2) concentrations. However, the absolute magnitude of the LD(CBF) change was independent of CO(2) concentration. The temporal dynamics of the LD(CBF) response during hypercapnia were significantly prolonged compared to baseline conditions (P<0.05).     

Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.     

Nimodipine posttreatment does not increase blood flow in rats with focal cortical ischemia

We used laser-Doppler flowmetry to study the effect of nimodipine administered after the onset of focal cortical ischemia on regional cerebral blood flow in 16 halothane-anesthetized, mechanically ventilated Wistar rats. We selected the Wistar rats strain since it would provide a wide range of ischemia severities to test the vascular response to nimodipine. Laser-Doppler probes continuously recorded regional cerebral blood flow at two or three sites over the parietal cortex (dura intact) while brain temperature was regulated at 37 degrees C. Occlusion of the right middle cerebral and common carotid arteries reduced cerebral blood flow to a mean of 38% (range 13-77%) of baseline. Thirty minutes later, either 2 micrograms/kg/min nimodipine (n = 8) or its vehicle, polyethylene glycol 400 (n = 8), was administered by a continuous intravenous infusion. Over 60 minutes of treatment, both the nimodipine-treated and vehicle-treated groups showed a trivial (3%) mean increase in cerebral blood flow. Nimodipine failed to augment cerebral blood flow regardless of whether the cortex was severely, moderately, or mildly ischemic.     

Functional recruitment of red blood cells to rat brain microcirculation accompanying increased neuronal activity in cerebellar cortex

Scanning laser-Doppler flowmetry (SLDF) combines laser-Doppler flowmetry and laser scanning to provide images of cerebral blood flow (CBF) with high spatial and temporal resolution. We investigated the contribution of single vascular elements to the local increase of CBF accompanying increased neuronal activity in halothane-anesthetized rats. CBF was examined in the cerebellar cortex under control conditions and in response to electrical stimulation of parallel and climbing fibers. At rest, arterioles contributed 9%, venules 11-13% and small vessels (< 20 microm) 8-14%, while the background constituted 64-72% of the total SLDF signal. During activation the background signal decreased to 55-60% while the signal from arterioles increased to 11-12%, from venules to 14-15% and from small vessels to 14-19%. The signal increase in small vessels that did not give any laser-Doppler signal at rest was due to functional recruitment of red blood cells to the capillary bed. We conclude that functional recruitment may be an integral part of the hemodynamic response accompanying neuronal activity.     

Lack of capillary recruitment in the brains of awake rats during hypercapnia

The present study investigates the question of whether increases in CBF induced by hypercapnia in awake rats are accompanied by increases in the number of perfused capillaries. For the detection of perfused capillaries, gamma-globulin-coupled fluorescein isothiocyanate was injected intravenously. In 10 brain structures the density of perfused capillaries per square millimeter was determined from coronal sections using a highly sensitive fluorescent microscopical method that, in contrast to others, avoided air drying of the frozen brain sections. The results showed an inhomogeneous local distribution of the density of perfused capillaries during normo- and hypercapnia. The density of perfused capillaries was unchanged during hypercapnia compared with normocapnia, although blood flow was markedly increased. It is concluded that a capillary recruitment does not exist in the brain during the high-flow situation of hypercapnia.     

Streptokinase treatment versus calcium overload blockade in experimental thromboembolic stroke

Thromboembolic brain ischemia was produced in dogs using an autologous blood clot model. The effect of postembolic treatment with flunarizine and streptokinase on hemispheric cerebral metabolic rate for oxygen (CMRO2), oxygen extraction ratio (OER), and cerebral blood flow (CBF) was studied by positron emission tomography (oxygen-15 technique) 24 hours after the insult. We studied five groups of experimental dogs and compared them with a control group of nonembolized dogs. Group I received no treatment, Group II was treated locally with 500,000 IU streptokinase starting 30 minutes after the insult, Group III received streptokinase locally 30 minutes after the insult and 0.1 mg/kg i.v. flunarizine immediately after the insult and 2 hours later, Group IV received flunarizine as Group III, and Group V was orally pretreated with 0.5 mg/kg/day flunarizine during 2 weeks preceding embolization. Compared with the contralateral hemisphere, in the embolized hemisphere a significant reduction of CMRO2 (-25% to -40%) and CBF in normocapnia (-35%) and hypercapnia (-50%) was observed in Groups I, II, and V. In Groups III and IV, CMRO2, OER, and CBF of the embolized hemisphere were within the normal range during normocapnia and hypercapnia; the extent of the ischemic lesions was markedly less than in the other groups of experimental dogs. We conclude that flunarizine treatment after experimental thromboembolic stroke had a favorable influence on brain tissue. Chronic preventive flunarizine treatment failed to have a beneficial effect.     

Analysis of the effect of bilateral sympathetic stimulation of cerebral and cephalic blood flow in the dog

Unilateral stimulation of the cervical sympathetic in dogs had no effect on cerebral blood flow (CBF) measured by the venous outflow technique. Since this technique measured CBF from both cerebral hemispheres, small changes induced by unilateral stimulation could have been masked by a large constant CBF measured from the contralteral hemisphere. To test this possibility the effect of simultaneous bilateral sympathetic stimulation was studied when the dog was breathing either normal air or a gas mixture of 10%CO2. During normocapnia, no changes in CBF occurred; during hypercapnia CBF increased 19% following passively the increase in blood pressure. These data indicate that bilateral stimulation of extracranial sympathetic nerves does not exert a significant effect on CBF. We show mathematically and experimentally that unoccluded anastomses will cause CBF to appear to decrease in response to sympathetic stimulation. This may explain why others have observed changes in CBF during sympathetic stimulation.     

Estrogen provides neuroprotection in transient forebrain ischemia through perfusion-independent mechanisms in rats

BACKGROUND AND PURPOSE: Estrogen-related neuroprotection in association with animal models of transient forebrain and focal ischemia has been documented in several recent reports. Some of those studies indicated that part of that benefit was a function of improved intraischemic vasodilating capacity. In the present study we examined whether chronic estrogen depletion and repletion affected ischemic neuropathology through perfusion-independent mechanisms. METHODS: Normal, ovariectomized (OVX), and OVX female rats treated with 17beta-estradiol (E2) were subjected to 30 minutes of transient forebrain ischemia (right common carotid occlusion plus hemorrhagic hypotension) and reperfusion. Neurological function and brain histopathology were assessed over the 72-hour recovery period. In all rats, preischemic and intraischemic cortical cerebral blood flow (CBF) levels were monitored with laser-Doppler flowmetry. In additional rats, CBF changes in the striatum and hippocampus were also monitored with laser-Doppler flowmetry probes and radiolabeled microspheres. In each experiment, the level of ischemia was targeted to a 75% to 80% reduction in cortical CBF. RESULTS: The similarity in ischemic severity among groups was supported by measurements of comparable patterns of electroencephalographic power changes during the ischemic period. Compared with normal females, OVX rats showed diminished neurological outcomes and more severe histopathology in the hippocampus and striatum. Two-week treatment of OVX rats with E2 was accompanied by postischemic neuropathological changes similar to those seen in normal females. Intraischemic CBF reductions in the hippocampus and striatum were similar in all groups (to 35% to 50% of the preischemic value) but significantly less than the cortical CBF reductions. CONCLUSIONS: These findings indicate that estrogen provides ischemic neuroprotection through mechanisms unrelated to improvement of intraischemic cerebral perfusion.     

The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis

BACKGROUND AND PURPOSE: The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P(ET)CO(2)) on MCA diameter and CFV. METHODS: Twelve subjects participated in a CO(2) manipulation protocol and/or an LBNP protocol. In the CO(2) manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO(2) (hypercapnia), or they hyperventilated to approximately 25 mm Hg P(ET)CO(2) (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of -20 and -40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols. RESULTS: Compared with normocapnia, hypercapnia produced increases in both P(ET)CO(2) (from 36+/-3 to 40+/-4 mm Hg, P<0.05) and CFV (from 63+/-4 to 80+/-6 cm/s, P<0.001) but did not change MCA diameters (from 2.9+/-0.3 to 2.8+/-0.3 mm). Hypocapnia produced decreases in both P(ET)CO(2) (24+/-2 mm Hg, P<0.005) and CFV (43+/-7 cm/s, P<0.001) compared with normocapnia, with no change in MCA diameters (from 2.9+/-0.3 to 2.9+/-0.4 mm). During -40 mm Hg LBNP, P(ET)CO(2) was not changed, but CFV (55+/-4 cm/s) was reduced from baseline (58+/-4 cm/s, P<0.05), with no change in MCA diameter. CONCLUSIONS: Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in P(ET)CO(2).     

Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex.

Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [C]iodoamphetamine technique, and 1/tau(c) values obtained using LSF, and used 1/tau(c) values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution.     

The effects of graded hypercapnia on the activation flow coupling response due to forepaw stimulation in α-chloralose anesthetized rats

Activation flow coupling (AFC), changes in cerebral blood flow (CBF) due to changes in neural activity with functional stimulation, provides the physiological basis of many neuroimaging techniques. Hypercapnia leads to an increase in CBF while neural activity remains unaffected. Laser Doppler (LD) flowmetry was used to measure CBF changes (LD_CBF) in the somatosensory cortex due to periodic electrical forepaw stimulation (4 s in duration) before and during graded hypercapnia (3% CO₂, 5% CO₂ and 10% CO₂). With increasing CO₂ concentrations, the baseline LD_CBF progressively increased. The peak height (PH) of the LD_CBF response, expressed as a percent change from the observed baseline for each hypercapnic state, significantly decreased (P<0.05) with increasing CO₂ concentrations. However, the absolute magnitude of the LD_CBF change was independent of CO₂ concentration. The temporal dynamics of the LD_CBF response during hypercapnia were significantly prolonged compared to baseline conditions (P<0.05).     

Effects of nitric oxide synthase inhibition on the cerebral circulation and brain damage during kainic acid-induced seizures in newborn rabbits.

The nitric oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), was used to investigate the effect of endogenous NO on the cerebral circulation and brain damage during kainic acid (KA)-induced seizures in newborn rabbits. The cerebral blood flow (CBF), by laser doppler flowmetry, cerebral oxygenation (concentrations of oxy-(HbO2), deoxy-(HbR) and total hemoglobin (tHb) in brain tissue), by near-infrared spectroscopy (NIRS), mean arterial blood pressure (MABP), electroencephalography (EEG), and hippocampal neuronal damage were evaluated. Pretreatment with L-NAME caused significant decreases in CBF, HbO2, and tHb, and a significant increase in HbR during KA-induced seizures, compared with pretreatment with saline (P < 0.05), without a significant difference in MABP. Our study also demonstrated that pretreatment with L-NAME reduced the seizure activity and neuronal cell death in the hippocampus elicited by the systemic administration of KA in the neonatal brain. These results suggest that NO is of major importance in the neurodestructive process in spite of its roles in maintaining both the CBF and cerebral oxygenation during KA-induced seizures in the neonatal brain.     

Long-term cortical CBF recording by laser-Doppler flowmetry in awake freely moving rats subjected to reversible photothrombotic stroke.

This study aimed at developing a laser-Doppler flowmetry (LDF) device suitable for long-term cortical cerebral blood flow (cCBF) measurement in awake, freely moving rats. The device included a flow probe adapter for permanent fixation to the skull bone and a connector that held the flow probe in the adapter in exactly the same position during repeated cCBF recordings. With this LDF recording system, cCBF values were stable and unaltered in awake, freely moving rats up to 4 days after operation compared with initial recordings during anesthesia. Repeated cCBF measurements in rats after transient removal and reattachment of the flow probe revealed a coefficient of variation of 7.0-17.4%. The LDF recording system was applied to rats subjected to a photothrombotic ring stroke lesion. cCBF in the region-at-risk declined to 59-34-26-33% of baseline values (P < 0.01) at 1-2-24 48 h after irradiation with gradually restored cCBF values of 56-87% at 72-96 h post-irradiation (P < 0.01 vs. 24 h). Transcardial carbon black perfusion examination of the brains confirmed the sustained hypoperfusion in the region at risk up to 48 h post-ischemia followed by a consistently occurring late spontaneous reperfusion. In conclusion, a novel laser-Doppler cortical CBF recording system has been set up that allows stable long-term cortical CBF follow-up in awake, freely moving rats.     

Cerebrovascular consequences of altering serotonergic transmission in conscious rat

Many therapeutic strategies aim at altering serotonin brain levels. However, serotonin (5-HT) is known to influence the cerebral circulation. The purpose of this study was to determine the effects of acutely decreasing intracerebral serotonin release upon cerebral blood flow and cerebrovascular reactivity to hypercapnia in conscious rats. To this end, (1) we analyzed the time-course of cortical blood flow changes measured with laser-Doppler flowmetry following injection of 0.1 mg kg⁻¹ 8-OHDPAT (5-HT_1A agonist), and (2) we evaluated the cerebrovascular reactivity to hypercapnia using a quantitative multiregional diffusible tracer technique 5 and 60 min following 8-OHDPAT administration. 8-OHDPAT induced a rapid and transient increase in cortical blood flow (+34%) that was prevented totally by WAY100135 (5-HT_1A antagonist) pre-treatment. Five min following 8-OHDPAT administration, the cerebrovascular responsiveness to hypercapnia was increased significantly in striatum (+27%) and fronto-parietal cortex (+61%). This result is consistent with a vasoconstrictor role of the serotonergic system that becomes manifest during hyperemic conditions.     

Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg, respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/- 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.