Inhibitory effect of methyl ethyl ketone upon the enhancement of cerebral blood flow during status epilepticus induced by lithium-pilocarpine

Significant increases in local cerebral blood flow during lithium-pilocarpine (Li-P) induced seizure have been reported. We recently found that both acetone and methyl ethyl ketone (MEK) showed anticonvulsive effects in status epilepticus induced by Li-P in rats. In this study, we examined whether MEK also suppressed the enhancement of local cerebral blood flow induced by Li-P with a simplified autoradiographic method using [¹⁴C]-para-iodo-N-isopropyl amphetamine ([¹⁴C]-IMP). Significant increases in local cerebral blood flow in the thalamus, hypothalamus, hippocampus and cerebellum were observed in Li-P induced status epilepticus rats. Pretreatment with MEK (8 mmol/kg) completely suppressed the enhancement of local cerebral blood flow to or below the control level in all regions.     

Effects of increasing arterial pressure on cerebral blood flow in the baboon: Influence of the sympathetic nervous system

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid¹³³Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation.In a control group of five baboons blood flow increased by 53±9% (mean ±S.E.) from the base line values in the arterial pressure range 130–159 mm Hg.In four baboons subjected to unilateral sympathetic stimulation flow increased by 16±4% in the same pressure range.In three babbons subjected to bilateral sympathetic stimulation there were not significant increases in flow until the arterial pressure had increased above 159 mm Hg.Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon.These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.These investigations were supported by the Medical Research Council and Tenovus (Scotland)     

Influence of posture on middle cerebral artery mean flow velocity in humans

We determined middle cerebral artery, common carotid artery and temporal superficial artery Doppler derived flow velocities in ten subjects for 10 min after change in posture. Maximal changes were observed after about 3 min. The 10° head-down tilt position increased blood velocities in the common carotid artery by 13% (SD 4)% (P < 0.001), in the middle cerebral artery by,6% (SD 3)% (P < 0.001) and in the superficial temporal artery by 70% (SD 26)% (P < 0.001). In the standing position, there was an 18% (SD 9)% (P < 0.001) decrease in the common carotid blood velocities, with 14% (SD 6)% (P < 0.001) and 53% (SD 23)% (P < 0.001) reductions in the middle cerebral and superficial temporal artery velocities, respectively. At 9 min after the changes in posture, velocities in the middle cerebral artery were at the value of supine rest, whereas the common carotid blood velocity was not completely restored and deviations in the temporal artery velocity persisted. The data would suggest that cerebral blood flow is regulated with some delay and that such regulation is partially reflected in the common artery blood flow, since changes in a branch of the external carotid artery flow velocity remained.     

LSCI检测不同缺血期对大鼠缺血再灌注过程脑血流的影响

目的　考察不同缺血期对大鼠缺血再灌注过程脑血流的影响。 方法　通过激光散斑成像技术（LSCI）检测大鼠大脑中动脉不同栓塞时间后,对再灌注过程中脑血流的影响,并对再灌注过程中的低灌注状态、无复流现象、血流流速及管径变化进行研究分析。 结果　2 h的栓塞后,大鼠脑部血流量趋向低灌注状态,约为栓塞前血流基值的(35±10)%;栓塞时间越长,无复流现象越多;在再灌注期间,缺血2 h组的血流比0.5 h组的低灌注水平低10%。 结论　长时间的脑缺血期再灌注过程可能是造成脑损伤程度加重的主要原因之一。LSCI可应用于脑部血流实时监测,操作简便,成像灵敏、稳定,结果可靠。     

Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF‐CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look‐Locker flow‐sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBV_a) using sequence parameters optimized for each contrast. Changes in total CBV (CBV_tot) were measured using a gadolinium‐based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF‐CBV_tot coupling constant α_tot was measured as 0.16 ± 0.14 and the CBF‐CBV_a coupling constant α_a was measured as 0.65 ± 0.24. Using a two‐compartment model of the vasculature (arterial and venous), the change in venous CBV (CBV_v) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD.     

Optimising the methodology of calculating the cerebral blood flow of newborn infants from near infra-red spectrophotometry data

Cerebral blood flow can be measured in neonates by near infra-red spectrophotometry. The tracer is oxyhaemoglobin. The purpose of the study is to compare the test-retest variability of two previously proposed methods (UCH and COP) of analysis, and to investigate the influence of sampling rates, smoothing and integration periods. Under clinical conditions good measurements are often difficult to obtain. Therefore, a second goal is to find ways of determining the quality of individual measurements. 380 cerebral blood flow measurements from 69 infants are analysed. The data set is optimised statistically for the lowest test-retest variability and the following results are obtained. The test-retest variability of measurements at 2 s sampling time data is considerably worse than at 0·5 s sampling time. Smoothing does not change the test retest variability. A 6 s integration period gives higher values and higher test-retest variability than an 8 s integration period. By applying the suggested criteria, a test-retest variability of 17% is achieved, if 50% of the measurements are rejected. The mean cerebral blood flow is 12·2 ml(100 g)⁻¹ min⁻¹ for the UCH method and 97·7 ml(100 g)⁻¹ min⁻¹ for the COP method. The test-retest variability of both methods is comparable for 0·5 s sampling time. For 2 s sampling time the method proposed by Skov et al. is significantly better. These test retest variabilities represent maximum values, part of the observed variability may be due to physiological changes of unknown magnitude.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

高压氧对脑缺血动物脑微循环及脑皮质血流量的影响

高压氧对脑缺血动物脑微循环及脑皮质血流量的影响１蔺世龙２刘景昌２冶建宏２近年来，国内外学者在缺血性脑损伤的研究方面进行了不少探讨，其中临床使用高压氧治疗缺血性脑损伤已经取得明显疗效［１］，同时对缺血性脑损伤机理的研究亦取得了有意义的结果［１～６］。本...     

Visually evoked blood flow responses and interaction with dynamic cerebral autoregulation: Correction for blood pressure variation

Visually evoked flow responses recorded using transcranial Doppler ultrasonography are often quantified using a dynamic model of neurovascular coupling. The evoked flow response is seen as the model's response to a visual step input stimulus. However, the continuously active process of dynamic cerebral autoregulation (dCA) compensating cerebral blood flow for blood pressure fluctuations may induce changes of cerebral blood flow velocity (CBFV) as well. The effect of blood pressure variability on the flow response is evaluated by separately modeling the dCA-induced effects of beat-to-beat measured blood pressure related CBFV changes.Parameters of 71 subjects are estimated using an existing, well-known second order dynamic neurovascular coupling model proposed by Rosengarten et al. [1], and a new model extending the existing model with a CBFV contributing component as the output of a dCA model driven by blood pressure as input.Both models were evaluated for mean and systolic CBFV responses. The model-to-data fit errors of mean and systolic blood pressure for the new model were significantly lower compared to the existing model: mean: 0.8% ± 0.6 vs. 2.4% ± 2.8, p < 0.001; systolic: 1.5% ± 1.2 vs. 2.2% ± 2.6, p < 0.001. The confidence bounds of all estimated neurovascular coupling model parameters were significantly (p < 0.005) narrowed for the new model.In conclusion, blood pressure correction of visual evoked flow responses by including cerebral autoregulation in model fitting of averaged responses results in significantly lower fit errors and by that in more reliable model parameter estimation. Blood pressure correction is more effective when mean instead of systolic CBFV responses are used. Measurement and quantification of neurovascular coupling should include beat-to-beat blood pressure measurement.     

Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats

Summary Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic ¹⁴C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25–94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.     

Deficient adjustment of cerebral blood flow to cognitive activity due to chronically low blood pressure

The present study aimed to investigate aberrances in the adjustment of cerebral blood flow to cognitive activity due to chronically low blood pressure. By means of transcranial Doppler sonography blood flow velocities in both middle cerebral arteries (MCA) were recorded during the execution of a serial subtraction task in 40 subjects with constitutional hypotension and 40 normotensive control persons. Additionally, blood pressure was continuously monitored. As a main result significant correlations between the task-induced changes in blood pressure and those in MCA blood flow velocities were found in hypotensives, but not in control subjects. The dependence of the regulation of cerebral blood flow on blood pressure points towards deficits in cerebral autoregulation in hypotension. Over the total sample the extent of the task-induced MCA flow velocity increase was positively related to cognitive performance. This underlines the importance of the adjustment of cerebral blood flow to current demands for optimal cognitive functioning.     

Local cerebral glucose utilisation following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow

The effects on local cerebral blood flow (LCBF) and glucose utilisation (LCGU) of permanent, bilateral carotid artery ligation (BCAL) were studied in conscious Wistar rats. LCBF and LCGU were measured using quantitative autoradiographic ¹⁴C-iodoantipyrine and the ¹⁴C-2-deoxyglucose (¹⁴C-DG) techniques in 24 anatomically discrete regions of the brain. LCBF in the cerebral hemispheres 2.5 h (acute) after BCAL significantly decreased to 25–87% of the sham control, with the exception of the mammillary body. After acute BCAL, there was a heterogeneous accumulation of ¹⁴C-DG in the caudate nucleus and cerebral cortices. Only in the lateral geniculate body did LCGU significantly decrease after BCAL. One week (chronic) later, LCBF was significantly decreased in 15 (containing the caudate nucleus and all the cerebral cortices) of 24 structures. LCGU in ten (containing the caudate nucleus and all the cerebral cortices) of 24 structures after chronic BCAL significantly decreased to 66–77% of the sham control, except for regions with neuronal damage in which there was a heterogeneous uptake of ¹⁴C-DG. The ratio of LCBF/ LCGU in chronic BCAL was unchanged in comparison with values in the corresponding sham-operated group. This model of acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism, is expected to become a pertinent tool for the neurophysiologist.     

Interactions between systemic hemodynamics and cerebral blood flow during attentional processing

The study explored interactions between systemic hemodynamics and cerebral blood flow during attentional processing. Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries (MCA) of both hemispheres were recorded while 50 subjects performed a cued reaction time task. Finger arterial pressure and heart rate were also continuously monitored. Doppler sonography revealed a right dominant blood flow response. The extent of the increase measured in second two of the interstimulus interval showed a clear positive association with reaction speed. Task‐related changes in blood pressure and heart rate proved predictive of changes in MCA flow velocities in limited time windows of the response. Besides an association between cerebral blood flow and attentional performance, the results suggest a marked impact of systemic hemodynamics on the blood flow response. All observed interactions are highly dynamic in time.     

Thermal method for continuous measurement of cerebral perfusion

A new thermal system using constant heating power for continuous measurement of cerebral perfusion is presented. It is designed and implemented for optimal perfusion sensitivity and dynamic response based on heat-transfer analysis of perfused brain tissue with thermistors on the cortical surface. Two matched thermistors are used, one to serve as a perfusion sensor and the other to compensate for the base-line temperature changes. To improve the signal-to-noise ratio of the measurement system, lock-in amplifiers are used to minimise long-term drift and low-frequency noise. Errors in the measurement caused by electrical and thermal fluctuations are tested and analysed. In vitro tests show that the measurement accuracy of temperature change is better than 10⁻³°C, and the temperature resolution is even greater. In vivo evaluation confirms that the system is responsive to cerebral perfusion changes associated with sudden changes in mean arterial blood pressure caused by bolus injection of norepinephrine, blood withdrawal and blood infusion. The dynamic response of the system is sufficient to detect the autoregulatory perfusion changes in response to arterial blood pressure alteration and the oscillations of cerebral blood flow.     

Frequency-domain analysis of cerebral autoregulation from spontaneous fluctuations in arterial blood pressure

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in crebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n=23) or impaired (group B, n=21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables in demonstrated by mean values of squared coherence >0.50 for both groups in the frequency range 0.02–0.50 Hz. However, group A has significanlty smaller coherences than group B in the frequency ranges 0.02–0.10 Hz and 0.33–0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3±1.05 and 1.80±1.2 rad Hz⁻¹, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25–0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.     

Influence of changes in the acid-base composition of the ventricular system on cerebral blood flow in cats

Summary In ventriculo-cisternal perfusion experiments performed in mechanically ventilated cats maintained under nitrous oxide anesthesia, the bicarbonate concentration of the ventricular perfusion fluid was decreased (from 21 to 4 mmol/l) or increased (from 21 to 84 mmol/l) during time intervals ranging from 45 to 120 min. The blood flow was measured in the caudate nucleus with two different methods: in a first series of experiments the temperature difference was continuously measured between a heated thermojunction and a reference junction, both devices being placed symmetrically in the right and left caudate nucleus (heat clearance method), while in a second series of experiments, the local blood flow was estimated from the rate of clearance of¹³³Xenon injected in micro-amounts (8–10 l) into the caudate nucleus. A decrease in the bicarbonate concentration of the ventricular perfusion fluid increased the blood flow in the caudate nucleus, estimated by both methods, while an increase in the bicarbonate concentration produced the opposite effect. The same alterations in the bicarbonate concentration of the ventricular perfusion fluid produced no detectable change in the hemispheric cerebral blood flow, measured by the clearance of¹³³Xenon injected into the carotid system.Finally, the bicarbonate concentration was independently altered in one of the lateral ventricles during bilateral ventricular perfusions, and changes in the blood flow distribution were studied in the caudate nuclei with a particle distribution method (⁸⁵Sr or¹⁴¹Ce labeled carbonized microspheres injected into the left heart ventricle). A ventricular perfusion, asymmetric with respect to the bicarbonate concentration induced an uneven distribution of the microspheres and hence of the local blood flow between both caudate nuclei. The results of the present experiments clearly argue in favour of a local influence of tissue pH on the blood flow in paraventricular gray matter.An abstract of this work was presented at the International Symposium on cerebral blood flow regulation, acid-base and energy metabolism in acute brain injuries held in Rome-Sienna, October 1971.     

The cholinergic pathway to cerebral blood vessels

Summary The effect of stimulating the greater superficial petrosal nerve (g.s.p.n.) upon retroglenoid venous blood flow has been tested in anaesthetized, paralysed and artificially ventilated rats. In 11 out of 15 tests, blood flow increased by an average of 25% with a time to peak response of 28 s. This response was abolished with the injection of atropine 0.1 mg kg^–1 injected intra-arterially. With both petrosal nerves intact, the administration of 6–7% CO₂ in air or 15% O₂ in N₂ caused average increases in blood flow of 105% and 45% respectively. These responses were not affected by bilateral section of the g.s.p.n. Similar experiments were carried out in 5 anaesthetized, spontaneously breathing rabbits in which, in addition toPaCO₂ andPaO₂,PO₂,PCO₂ and blood flow in the caudate nucleus were measured continuously using chronically implanted mass spectrometer catheters and heated thermistors. Caudate nucleus blood flow increased in response to hypoxia and hypercapnia and this response was not significantly affected by section of one or both g.s.p.n., sinus or vagus nerves. With section of sinus and vagus nerves, blood flow changed passively with arterial pressure.     

Perception of posture and cerebral blood flow.

The perception of posture in man is made possible by the information of the vestibular organs, the visual system, the proprioception and the blood volume distribution. The present study examined the cerebral blood flow velocity (CBFV) and the fluid volume of the thoracic cavity under different pressure conditions and their effects on the perception of posture. Changes in blood flow velocity were measured by transcranial Doppler sonography (TCD), and changes in the blood volume distribution of the upper torso were registered by impedance plethysmography. The results indicated that the cerebral blood flow volume and the thoracic blood volume changed in the same manner. Lower Body Positive Pressure (+30 mmHg) led to an increase in central volume and CBFV. During the Lower Body Negative Pressure Treatment (-30 mmHg), the central blood volume and the cerebral blood flow velocity decreased while venous pooling occurred. Additionally, the changes in both parameters were associated with an altered posture perception. The correlations between the SHP and the two physiological parameters cerebral blood flow velocity and fluid shift in the upper thorax indicate that the fluid shift in the thoracic cavity was more closely related to the SHP than to the changes in cerebral blood volume.     

A cellular mechanism for myogenic regulation of cat cerebral arteries

Autoregulation of cerebral blood flow is accomplished through integration of metabolic, neurogenic and myogenic mechanisms. Myogenic mechanisms involve activation of cerebral arterial muscle cells as transmural pressure increases, providing a means through which vessel caliber can be regulated to maintain blood flow constant. The cellular mechanisms involved in this myogenic response may involve changes in the electrical potential across the plasma membrane. When isolated cat middle cerebral arteries are cannulated and prepared in a manner allowing manipulation of transmural pressure, the muscle cell membrane depolarizes as pressure increases. The degree of membrane depolarization in response to an elevated pressure is dependent upon extracellular Ca²⁺ ([Ca]₀), increasing as [Ca]₀ is elevated and markedly decreasing as [Ca]₀ is reduced to low levels. When these arterial preparations are maintained at a physiological pressure of around 100 mm Hg, spontaneous action potentials can be recorded which increase in frequency upon further elevation in pressure. Vessels exhibiting such electrical activity can be observed to decrease in diameter as pressure is increased. Such finding suggest a membrane electrical mechanism for myogenic autoregulation of cerebral arteries.     

Effects of endothelin receptor type A antagonism and nitric oxide synthase inhibition on cerebral blood flow in hypertensive rats

Effects of the endothelin receptor type A antagonist BQ 123 and the NO synthase inhibitor L -NMMA on cerebral blood flow were studied in vivo in anaesthetized hypertensive (SHR) and normotensive (WKY) rats. The effects of acetylcholine following pre-treatment with these drugs were also studied with the microsphere method for blood flow determination in the cortex, thalamus, caudatus, pons, medulla, cerebellum and hypophysis. BQ 123 (1 mg kg^?1) induced only minor effects on cerebral blood flow in both strains (n = 8), whereas L -NMMA (N = 8; 20 mg kg^?1) reduced regional cerebral blood flow significantly in most regions (21–54%) in the hypertensive, but not in the normotensive rat. In normotensive rats pre-treated with BQ 123 intravenous administration of acetylcholine (2 μg kg^?1 min^?1) induced a widespread significant increase (20–50%) in cerebral blood flow despite a reduction of the mean arterial blood pressure, while no significant effects were seen in hypertensive animals. Intravenous infusion of acetylcholine in animals pre-treated with L -NMMA did not affect cerebral blood flow in most regions in either of the two rat strains. In conclusion, a vasodilatory response to acetylcholine was found following endothelin receptor A antagonism in the WKY rat only, suggesting a role for endothelin in the control of cerebral blood flow in this strain. Furthermore, a higher basal vasodilating nitric oxide-tone seems to be present in the hypertensive rat compared with the normotensive rat.