GM1 Acupoint Injection Improves Mental Retardation in Children with Cerebral Palsy.

To study the clinical effectiveness and mechanism of GM1 acupoint injection therapy on mental retardation for children with cerebral palsy (CP). A total of 90 children with CP were divided into acupoint injection group (group A), subcutaneous injection group (group B), and control group (group C). Another 30 healthy children were set as a healthy control group (group D). The Mental Developmental Index (MDI), Psychomotor Developmental Index (PDI), and hemodynamic parameters in the cerebral arteries were measured before and after treatment. After three treatment courses, the MDI and PDI in groups A, B, and C were increased, and the increase in group A was most obvious (P < 0.05). Peak systolic velocity, mean velocity, and end-diastolic velocity were also elevated in group A, and after three treatment courses, resistance index decreased with a statistical significance (P < 0.05). However, there were no significant changes in groups B and C (P > 0.05). For all groups, neuron-specific enolase levels decreased and total superoxide dismutase increased after treatment. Acupoint injection therapy combined with conventional rehabilitation therapy demonstrated significant effects on cerebral hemodynamic conditions for children with CP.

Reversal of cerebrovascular constriction in experimental cerebral malaria by L-arginine.

Vascular dysfunction associated with low nitric oxide (NO) biavailability and low plasma L-arginine levels is observed in both human and experimental cerebral malaria (ECM). In ECM, cerebrovascular constriction results in decreased pial blood flow and hypoxia, and administration of NO donors reverses constriction and increases survival. Supplementation of L-arginine, the substrate for NO synthesis by NO synthases, has been considered as a strategy to improve vascular health and act as adjunctive therapy in human severe malaria. We investigated the effect of L-arginine supplementation on pial vascular tonus of mice with ECM after direct superfusion on the brain surface or systemic delivery. Pial arteriolar diameters of Plasmodium berghei-infected mice with implanted cranial windows were measured using intravital microscopy methods, before and after L-arginine administration. Systemic delivery of L-arginine was performed intravenously, at 10, 50, 100 and 200 mg/kg, as bolus injection or slowly through osmotic pumps, combined or not with artesunate. Direct superfusion of L-arginine (10-7M, 10-5M and 10-3M) on the brain surface of mice with ECM resulted in immediate, consistent and dose-dependent dilation of pial arterioles. ECM mice showed marked cerebrovascular constriction that progressively worsened over a 24 h-period after subcutaneous saline bolus administration. L-arginine administration prevented the worsening in pial constriction at all the doses tested, and at 50 mg/kg and 100 mg/kg it induced temporary reversal of vasoconstriction. Slow, continuous delivery of L-arginine by osmotic pumps, or combined bolus administration of artesunate with L-arginine, also prevented worsening of pial constriction and resulted in improved survival of mice with ECM. L-arginine ameliorates pial vasoconstriction in mice with ECM.

A Functional Near-Infrared Spectroscopy Study of High-Frequency Yoga Breathing Compared to Breath Awareness.

BACKGROUND High-frequency yoga breathing (breath rate of 2.0 Hz) has been associated with changes in oxy-hemoglobin in the prefrontal region of the brain. The present study assessed the effects of high-frequency yoga breathing (HFYB) at 1.0 Hz on frontal oxy-hemoglobin (oxy-Hb) and deoxy-hemoglobin (deoxy-Hb). MATERIAL AND METHODS Forty healthy male participants were recruited for the study. The experimental group consisted of 20 participants 23-40 years old (group mean ±S.D., 26.4±4.7 years) with at least 3 months of experience performing HFYB (group mean ±S.D., 16.3±9.8 months). The control group consisted of 20 participants ages 23-38 years (group mean age ± S.D., 27.4±4.1 years), who were seated quietly for the same duration and their average experience of yoga practice was (±S.D.) 4.3±2.7 months. Each participant in the experimental group was assessed at 2 sessions (HFYB and breath awareness [BAW]) on alternate days. Hemodynamic changes were assessed using a functional near-infrared spectroscopy sensor placed over the forehead. Data were analyzed using repeated-measures analyses of variance followed by post hoc Bonferroni adjustment. RESULTS A significant reduction was observed in oxy-Hb during and after HFYB on the left and right sides compared to values before. We also found a significant reduction in deoxy-Hb during and after the quiet sitting control session compared to pre-session values on left and right sides. CONCLUSIONS The decrease in oxy-Hb during and after HFYB suggests that there was no frontal activation during HFYB when practiced at the rate of 1.0 Hz.

Effects of acupuncture at GB20 on CO2 reactivity in the basilar and middle cerebral arteries during hypocapnia in healthy participants.

OBJECTIVES: The acupoint GB20 is known to affect vertebrobasilar blood flow regulation. However, no previous study has used transcranial Doppler imaging to examine whether acupuncture at GB20 has a selective effect on blood flow in various cerebral arteries, such as the basilar artery (BA) and the middle cerebral arteries (MCAs). Therefore, this study sought to determine the specific effects of GB20 acupuncture on cerebral blood flow (CBF). MATERIALS AND METHODS: Blood flow velocity and CO(2) reactivity were measured by transcranial Doppler imaging with a 2-MHz pulsed Doppler probe observed through both temporal windows for the MCAs and through the suboccipital window for the BA before and after GB20 acupuncture treatment in 15 healthy young male volunteers. The changes in hyperventilation-induced CO(2) reactivity and corrected blood flow velocities at 40 mmHg (CV40) were assessed for the BA and both MCAs. Blood pressure and heart rate were measured before and after the acupuncture treatment. RESULTS: CO(2) reactivity in the BA increased significantly after GB20 acupuncture treatment compared with baseline (p=0.041). In contrast, CO(2) reactivity in both MCAs remained unchanged. The CV40 in the BA and the MCAs showed no change after the GB20 acupuncture treatment. The mean heart rate decreased significantly after the GB20 acupuncture, whereas the mean blood pressure showed no change. CONCLUSIONS: This study demonstrated that acupuncture treatment on GB20 increases CO(2) reactivity specifically in the BA, with no effect in the MCAs. These results clinically support the use of GB20 to treat disorders of posterior cerebral circulation and support the idea that particular acupoints affect specific brain regions and cerebral arteries.

Difference in cerebral blood flow velocity in neonates with and without hyperbilirubinemia.

PURPOSE: To evaluate the difference in cerebral blood flow velocity (CBFV) in neonates with and without hyperbilirubinemia. METHODS: CBFV of 70 healthy late-preterm and term newborns with unconjugated hyperbilirubinemia (UCH) reaching the threshold of phototherapy requirement was compared with 70 gestational- and postnatal age-matched controls without hyperbilirubinemia. Resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were measured in internal carotid, vertebral and middle cerebral arteries by transcranial color Doppler ultrasound at the beginning of phototherapy, after 48-72h of starting phototherapy and at 5-7days after its stoppage. In controls CBFV was assessed once at inclusion. RESULTS: Both the groups were comparable. An increase in CBFV (decreased RI and PI, increased PSV and vasodilation) was observed in the UCH group. A further increase in CBFV was noticed after 48h of phototherapy. After 5-7days of stoppage of phototherapy, though there was a significant reduction in CBFV in mild-to-moderate UCH (serum bilirubin ⩽25mg/dL), in severe UCH (serum bilirubin >25mg/dL), CBFV remained increased. Four neonates developed features of acute bilirubin encephalopathy and had significantly higher CBFV compared to those with normal outcome. CONCLUSIONS: An increase in CBFV was observed in neonates with UCH compared to those without hyperbilirubinemia.

Effects of N-acetyl-L-cysteine and hyaluronic acid on HBOC-201-induced systemic and cerebral vasoconstriction in the rat.

Hemoglobin-based oxygen carrier-201 (HBOC) was developed as a resuscitative fluid but concerns exist over potentially adverse vasoconstriction. This study evaluated whether concurrent IV (intra venous) N-acetyl-L-cysteine (NAC) or hyaluronic acid (HA) would attenuate HBOC-associated vasoconstriction, assessed by systemic blood pressures and cerebral pial microvasculature, when administered to healthy, anesthetized rats. Rats (8-9/group) received a 30 min infusion of 3 ml/kg HBOC, HBOC plus 600 mg/kg NAC (HBOC/NAC), HBOC plus 1.5 mg/kg HA (HBOC/HA) or 3 ml/kg Albumin. Mean (MAP) and systolic (SBP) blood pressures, blood chemistries and cerebral pial vessel diameters were measured at baseline, end of infusion, and intermittently for an additional 90 min. HBOC caused immediate and sustained increases in SBP and MAP (35.3 ± 3.6 and 29.1 ± 2.5 mm Hg peak increases above baseline, respectively; mean ± SEM) and immediate but progressive vasoconstriction (11 µm maximum reduction) in medium-sized (50-100 µm) pial arterioles. When NAC was co-administered, blood pressure changes were attenuated and vessel changes were abolished. Similar trends were noted with co-administration of HA but were not statistically different from HBOC-alone. Small-sized (< 50 µm) pial vessels and blood parameters showed no differences from baseline or among groups. No adverse clinical signs were observed. We demonstrated that it is possible for adjuvant drugs to reduce the vasoconstriction associated with HBOC-201. Coinfusion of the anti-oxidant NAC mitigated HBOC-201-associated increases in blood pressures and vasoconstriction in medium-sized cerebral pial vessels. The drag-reducing polymer HA may be more effective at a higher dose as a similar but non-significant trend was observed.

The influence of transcutaneous electrical neurostimulation (TENS) on human cerebral blood flow velocities.

BACKGROUND: It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in analogous ways. In this line of thought, cervical application of TENS might be a useful and simple adjunct in the treatment of cerebrovascular disease by improving cerebral blood flow. Experiments were performed in order to assess whether cervical TENS is safe and whether an effect on cerebral blood flow velocity (CBFV) can be shown in healthy subjects. METHOD: A controlled, non-randomized, phase 1 study was performed with 20 healthy volunteers. Cervical TENS was applied in several frequencies, with and without hyperventilation. Continuous registration of blood pressure, pulse, CBFV (estimated by transcranial Doppler sonography) and end-tidal carbon dioxide concentration was performed. FINDINGS: Cervical TENS was well-tolerated by all subjects. Despite small effects on heart rate (HR) and mean arterial blood pressure (MAP), a significant effect on middle cerebral artery (MCA) blood flow velocity was not demonstrated. No effect of age, gender, current or session order on MCA, HR, or MAP was found. TENS did not influence the effect of hyperventilation. CONCLUSIONS: In these experiments, application of cervical TENS is proven to be a safe procedure. However, no effects on cerebral blood flow velocity could be detected, perhaps due to the intact cerebral autoregulation in the healthy volunteers.

Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids.

The aim of our study was to investigate the adaptation of the hypothalamic circulation to chronic nitric oxide (NO) deficiency in rats. Hypothalamic blood flow (HBF) remained unaltered during chronic oral administration of the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 1 mg/ml drinking water) although acute NOS blockade by intravenous l-NAME injection (50 mg/kg) induced a dramatic HBF decrease. In chronically NOS blocked animals, however, acute l-NAME administration failed to influence the HBF. Reversal of chronic NOS blockade by intravenous l-arginine infusion evoked significant hypothalamic hyperemia suggesting the appearance of a compensatory vasodilator mechanism in the absence of NO. In order to clarify the potential involvement of vasodilator prostanoids in this adaptation, cyclooxygenase (COX) mRNA and protein levels were determined in the hypothalamus, but none of the known isoenzymes (COX-1, COX-2, COX-3) showed upregulation after chronic NOS blockade. Furthermore, levels of vasodilator prostanoid (PGI(2), PGE(2) and PGD(2)) metabolites were also not elevated. Interestingly, however, hypothalamic levels of vasoconstrictor prostanoids (TXA(2) and PGF(2alpha)) decreased after chronic NOS blockade. COX inhibition by indomethacin but not by diclofenac decreased the HBF in control animals. However, neither indomethacin nor diclofenac induced an altered HBF-response after chronic l-NAME treatment. Although urinary excretion of PGI(2) and PGE(2) metabolites markedly increased during chronic NOS blockade, indicating COX activation in the systemic circulation, we conclude that the adaptation of the hypothalamic circulation to the reduction of NO synthesis is independent of vasodilator prostanoids. Reduced release of vasoconstrictor prostanoids, however, may contribute to the normalization of HBF after chronic loss of NO.

Carbon monoxide from heme oxygenase-2 Is a tonic regulator against NO-dependent vasodilatation in the adult rat cerebral microcirculation.

Although the brain generates NO and carbon monoxide (CO), it is unknown how these gases and their enzyme systems interact with each other to regulate cerebrovascular function. We examined whether CO produced by heme oxygenase (HO) modulates generation and action of constitutive NO in the rat pial microcirculation. Immunohistochemical analyses indicated that HO-2 occurred in neurons and arachnoid trabecular cells, where NO synthase 1 (NOS1) was detectable, and also in vascular endothelium-expressing NOS3, suggesting colocalization of CO- and NO-generating sites. Intravital microscopy using a closed cranial window preparation revealed that blockade of the HO activity by zinc protoporphyrin IX significantly dilates arterioles. This vasodilatation depended on local NOS activities and was abolished by CO supplementation, suggesting that the gas derived from HO-2 tonically regulates NO-mediated vasodilatory response. Bioimaging of NO by laser-confocal microfluorography of diaminofluorescein indicated detectable amounts of NO at the microvascular wall, the subdural mesothelial cells, and arachnoid trabecular cells, which express NOS in and around the pial microvasculature. On CO inhibition by the HO inhibitor, regional NO formation was augmented in these cells. Such a pattern of accelerated NO formation depended on NOS activities and was again attenuated by the local CO supplementation. Studies using cultured porcine aortic endothelial cells suggested that the inhibitory action of CO on NOS could result from the photo-reversible gas binding to the prosthetic heme. Collectively, CO derived from HO-2 appears to serve as a tonic vasoregulator antagonizing NO-mediated vasodilatation in the rat cerebral microcirculation.

Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans.

To develop a method to measure the dynamic response of the serotonin system in vivo, the effects of intravenously administered citalopram (the most selective of the serotonin reuptake inhibitors) or clomipramine on cerebral blood flow (CBF) were evaluated. CBF was measured with positron emission tomography (PET) in 27 normal subjects scanned under baseline conditions and, on the same day, after an intravenous (IV) infusion of placebo, citalopram, or clomipramine using a randomized, double-blind design. The main effects of the drugs on blood flow occurred in the thalamus, hypothalamus, and cingulate cortex. Compared to placebo, clomipramine reduced blood flow in the mediodorsal and ventral lateral nuclei of the thalamus, whereas citalopram reduced blood flow in the pulvinar nucleus and the hypothalamus. Compared to clomipramine, citalopram decreased blood flow in the cingulate cortex. The findings support previous reports showing acute central effects of citalopram and clomipramine on regional serotonergic functions measured by PET. Acute side effects may, however, require that care is taken in the selection of experimental designs for future PET studies using IV administration of these antidepressants.

MDMA-evoked changes in cerebral blood flow in living porcine brain: correlation with hyperthermia.

3,4-Methylenedioxymethamphetamine (MDMA) acutely releases intraneuronal dopamine and serotonin and evokes hyperthermia which is linked to toxicity for serotonin fibers. The acute effects of MDMA on cerebral blood flow (CBF) in living brain have not been described in an animal model of MDMA intoxication. We predicted that MDMA-induced hyperthermia should correlate with increased CBF in the hypothalamus, a serotonin-rich brain region subserving thermoregulation. To test this prediction, we used positron emission tomography with statistical parametric mapping for exploratory analysis of the focal changes in the magnitude of CBF in the anesthetized female Landrace pig (n = 9) at 30 and 150 min after acute challenge with MDMA-HCl (1 mg/kg, i.v.). The MDMA treatment was followed by increased CBF in the occipital cortex and in the medial mesencephalon overlapping the dorsal raphé nucleus, and reduced CBF in the cerebellar vermis and in a cluster in the medulla encompassing the left locus coeruleus. The individual increase of body temperature correlated positively with increased CBF in the vicinity of the raphé nucleus, in the hypothalamus (regions linked to thermoregulation), and also in the medial frontal cortex, which together comprise the regions receiving the most dense serotonin innervations in pig brain. Thus, individual differences in the susceptibility to MDMA-induced hyperthermia in this population correlated with the magnitude of focal increases in CBF within specific brain regions endowed with a dense serotonin innervation, including regions linked to thermoregulation.

Effect of short-term phytoestrogen treatment in male rats on nitric oxide-mediated responses of carotid and cerebral arteries: comparison with 17beta-estradiol.

The use of estrogen for protection against vascular dysfunction is limited due to its effects on the reproductive system, particularly in males. We postulated that daidzein, an isoflavone with estrogen-like effects on the systemic vasculature but not the reproductive system, might enhance nitric oxide (NO)-mediated cerebral vasodilatation. Male rats were administered vehicle, 17beta-estradiol (0.1 mg/kg s.c.), or daidzein (0.2 mg/kg s.c.) daily for 7 days. Basal and acetylcholine-stimulated NO release was assessed in vitro via carotid arterial rings or in vivo by measuring changes in basilar artery diameter. Levels of protein expression of endothelial NO synthase (eNOS), caveolin-1, and calmodulin were assessed in carotid arteries using Western analysis. Plasma NO levels were doubled by daidzein or 17beta-estradiol. NO production and endothelium-dependent contraction in response to the NOS inhibitor NG-nitro-L-arginine (L-NNA; 100 microM) was enhanced by 50 to 100% in carotid arteries from rats treated with daidzein or 17beta-estradiol. Acetylcholine-induced relaxation was selectively enhanced in carotid arteries from rats treated with daidzein. Similarly, constrictor responses of the basilar artery to L-NNA in vivo were selectively augmented by approximately 100% by 17beta-estradiol treatment and tended to be approximately 50% greater in daidzein-treated rats. Expression of caveolin-1 was decreased, and calmodulin was increased, in vessels from daidzein- or 17beta-estradiol-treated rats. eNOS expression was unaffected by the treatments. These data suggest that short-term administration of daidzein or 17beta-estradiol modulates cerebral artery reactivity in males by enhancing synthesis and release of endothelium-derived NO. Isoflavone therapy may therefore be a feasible approach to protect against cerebrovascular disease and stroke.

Effect of moxibustion stimulation of various skin areas on cortical cerebral blood flow in anesthetized rats.

The effect of moxibustion stimulation of various skin areas (cheek, forepaw, upper arm, chest, back, lower leg, hindpaw and perineum) on cerebral blood flow (CBF) of the parietal cortex was examined in anesthetized rats after eliminating emotional influences. Moxibustion stimulation was performed by burning a moxa cone of about 4 mg weight placed on the shaved skin. CBF of the parietal cortex was measured using a laser Doppler flowmeter. Stimulation of the cheek, forepaw, upper arm and hindpaw produced significant increases in CBF, but stimulation of the other areas did not produce significant responses. Moxibustion stimulation of the forepaw and hindpaw produced an increase in the mean arterial pressure (MAP), while stimulation of the other areas did not. After spinal transection at the 2nd thoracic level, the MAP response to stimulation of the forepaw was abolished, whereas the CBF response to stimulation of the forepaw remained. The CBF response in spinalized rats was not affected by cutting cervical sympathetic and facial parasympathetic nerves, while it was almost abolished by intravenous administration of muscarinic and nicotinic cholinergic blocking agents. The CBF response was abolished by crushing the brachial plexus ipsilateral to the stimulated side. It is suggested that the increase in CBF, independent of MAP and emotional responses, elicited by moxibustion stimulation is a reflex response whose afferent pathway is composed of somatic afferent nerves, and whose efferent pathway involves intracerebral cholinergic nerves. A contribution of endogenous opioids in the present CBF responses was neglected, because naloxone did not influence the CBF responses.

Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat.

Plastic changes in motor cortex capillary structure and function were examined in three separate experiments in adult rats following prolonged exercise. The first two experiments employed T-two-star (T(2)*)-weighted and flow-alternating inversion recovery (FAIR) functional magnetic resonance imaging to assess chronic changes in blood volume and flow as a result of exercise. The third experiment used an antibody against the CD61 integrin expressed on developing capillaries to determine if motor cortex capillaries undergo structural modifications. In experiment 1, T(2)*-weighted images of forelimb regions of motor cortex were obtained following 30 days of either repetitive activity on a running wheel or relative inactivity. The proton signal intensity was markedly reduced in the motor cortex of exercised animals compared with that of controls. This reduction was not attributable to alterations of vascular iron levels. These results are therefore most consistent with increased capillary perfusion or blood volume of forelimb regions of motor cortex. FAIR images acquired during experiment 2 under normocapnic and hypercapnic conditions indicated that resting cerebral blood flow was not altered under normal conditions but was elevated in response to high levels of CO(2), suggesting that prolonged exercise increases the size of a capillary reserve. Finally, the immunohistological data indicated that exercise induces robust growth of capillaries (angiogenesis) within 30 days from the onset of the exercise regimen. Analysis of other regions failed to find any changes in perfusion or capillary structure suggesting that this motor activity-induced plasticity may be specific to motor cortex.These data indicate that capillary growth occurs in motor areas of the cerebral cortex as a robust adaptation to prolonged motor activity. In addition to capillary growth, the vascular system also experiences heightened flow under conditions of activation. These changes are chronic and observable even in the anesthetized animal and are measurable using noninvasive techniques.

Cerebral hemodynamic responses to betel chewing: a Doppler study.

We sought to evaluate cerebral hemodynamic responses to betel chewing. Thirty healthy male volunteers (mean age = 35 years), ten new chewers, ten occasional chewers, and ten chronic chewers were included in this study. We used carotid duplex sonography and transcranial Doppler to measure the flow velocities and flow volume (FV) of the common carotid (CCA), internal carotid (ICA), external carotid (ECA) arteries, and the flow velocity of middle cerebral artery (MCA). Blood pressure (BP) and heart rate (HR) were recorded simultaneously. All subjects were asked to chew fruit-flavored chewing gum for 10 minutes. Blood flows of the above vessels were measured four times at baseline and at the 2nd, 6th, and 12th minute after chewing. A repeated study was followed in the same subject but substituted with betel nut. Chronic chewers had delayed onset time and shortened vanishing time of facial-flushing sensation. Systolic and diastolic BPs were mildly elevated during gum chewing (p = 0.008 and 0.015, respectively), whereas diastolic BP was dropped during betel chewing (p = 0.008). Heart rate increased prominently during betel chewing (p < 0.0001), especially in new and occasional chewers. The peak systolic, end diastolic velocities, and FV in ECA and CCA increased significantly during betel chewing (p < 0.0001). The blood flows in the ICA and MCA had no significant changes during gum or betel chewing. Betel chewing has a central sympathetic effect resulting in accelerated HR, increased blood flows in ECA and CCA, but has a peripheral cholinergic effect resulting in a drop of diastolic BP. Intracranial cerebral hemodynamics is not affected during betel chewing. The inotropic and chronotropic effect to the heart from betel chewing is probably an unfavorable risk for patients with ischemic heart disease.

Different modes of manual acupuncture stimulation differentially modulate cerebral blood flow velocity, arterial blood pressure and heart rate in human subjects.

The psychophysiological effect of different modes of manual acupuncture stimulation was investigated in 12 healthy, right handed, male subjects (mean age 29). The cerebral blood flow velocity (CBFV) in both middle cerebral arteries, arterial blood pressure (BP), heart rate (HR) and the perceived intensity of the stimulation were monitored while an acupuncture needle in the right dorsal thenar muscle (point Hegu, Li 4) was repetitively rotated with either high frequency (4-8 Hz) and low amplitude (hf-la) or low frequency (1-2 Hz) and high amplitude (lf-ha). Response patterns induced by hf-la and 1f-ha [corrected] stimulation differed significantly (P < 0.05) as tested by Student's t-test: (1), 1f-ha [corrected] stimulation was perceived as more intense and induced a more marked right hemispheric CBFV increase; (2), while hf-la stimulation lead to a slight decrease of BP and HR, lf-ha stimulation induced an initial pressor response (increase of BP, decrease of HR) and a more marked long term decrease of BP. Data indicate that the mode of manual acupuncture stimulation has a differential effect on the perceived stimulation intensity, the cerebral activation and the cardiovascular reflex response.

New animal model for the study of postmenopausal coronary and cerebral artery function: the Watanabe heritable hyperlipidemic rabbit fed on a diet avoiding phytoestrogens.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy (ERT) on the functional characteristics of coronary and cerebral arteries in a new rabbit model for postmenopausal vascular function. METHODS: Female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomized to treatment for 16 weeks with either 17 beta-estradiol or placebo. The chow used was semi-synthetic, thereby avoiding the influence of phytoestrogens. Ring segments of cerebral and coronary arteries were mounted for isometric tension recordings in myographs. The passive and active length-tension relationships for electromechanical (high potassium), pharmacomechanical (histamine) and combined electro- and pharmacomechanical (high potassium plus histamine) contraction were evaluated. RESULTS: Treatment with 17 beta-estradiol significantly changed the active length-tension relationship for the electromechanical response in the proximal coronary arteries. No changes were observed for the passive length-tension relationships. CONCLUSIONS: Long-term treatment with 17 beta-estradiol lowered the electromechanical tonus of atherosclerotic coronary arteries proximally, where the atherosclerosis is most developed. This could be one of the mechanisms behind the putative protective effect of hormone replacement therapy against ischemic heart disease. The study presents a promising new animal model for the investigation of postmenopausal coronary and cerebral artery function. The data correspond well with epidemiological observations in postmenopausal women.

Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats.

We tested the hypothesis that long-term application of a Ca2+ channel blocker would ameliorate the functional and morphological deterioration of the cerebral arteries during hypertension. Male spontaneously hypertensive rats (SHR) were fed a standard rat chow, containing a low (3 mg/kg/day) or high dose (6 mg/kg/day) of benidipine, a Ca2+ channel blocker, for 2 months. Using a cranial window, we examined responses of the basilar artery to acetylcholine, sodium nitroprusside, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol (Y-26763; an opener of ATP-sensitive K+ channels), and (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632; an inhibitor of Rho-associated kinase). Mean arterial pressure of the control group was 193+/-5 mm Hg (mean+/-S.E.M.), while that of the low-dose benidipine group was 183+/-5 mm Hg and that of the high-dose group was 159+/-4 mm Hg. Dilator responses of the basilar artery to acetylcholine and Y-26763 were impaired in SHR compared with those of normotensive Wistar-Kyoto (WKY) rats and treatment with benidipine enhanced the vasodilator responses to acetylcholine and Y-26763 in SHR. Y-27632-induced dilatation of the basilar artery was enhanced in SHR compared to that in WKY rats and the vasodilatation was reduced by benidipine in SHR. Sodium nitroprusside caused similar dilatation of the basilar artery, in both WKY rats and the SHR control group, and benidipine did not affect nitroprusside-induced dilatation of the artery in SHR. The wall of the basilar artery was significantly thicker in SHR than in WKY rats and benidipine treatment reduced the wall thickness of the artery in SHR. These findings suggest that chronic treatment with a Ca2+ channel blocker may enhance the dilator capacity and reduce contractility of the basilar artery during hypertension. Benidipine may also ameliorate the morphological changes of the basilar artery in hypertension.

Blood capillary distribution correlates with hemodynamic-based functional imaging in cerebral cortex.

Our study concerns the mechanisms that underlie functional imaging of sensory areas of cortex using hemodynamic-based methods such as optical imaging of intrinsic signals, functional magnetic resonance imaging and positron emission tomography. In temporal cortex of chinchilla, we have used optical imaging of intrinsic signals evoked by acoustic stimulation to define the functionally responsive area and then made (scanning electron microscopy) observations of the corresponding capillary networks prepared by corrosion cast methods. We report that intrinsic signals associated with auditory cortex correlate directly with discrete capillary beds. These capillary beds, within the cortical surface layers, are distributed across the cortex in a non-uniform fashion. Within cortex both the arterial supply and the capillary network contain various flow control structures. Our study suggests a causal relationship between the metabolic demands of local neuronal activity and both the density of the capillary network and the placement of the control structures. Such relationships will affect the ultimate spatial resolution obtainable by hemodynamic-based functional brain imaging studies. These relationships will also affect quantitative comparisons of activity levels in different areas of cortex.

[Effects of active and passive movement stimuli on cerebral hemodynamics and the cerebral metabolism]. / Wirkungen kinetischer Stimuli auf die zerebrale Hämodynamik und den zerebralen Stoffwechsel am Beispiel von aktiven und passiv ausgeführten Bewegungen.

INTRODUCTION: In contrast to the well-examined cardiovascular changes during movement stimuli, up to now changes of cerebral hemodynamics and cerebral metabolism have rarely been studied. We investigated the question if active and passive movement stimuli cause changes in the cerebral hemodynamics and the cerebral metabolism. METHOD: Active and passive repetitive movement stimuli on 14 volunteers (8 females, 6 males, age 35 +/- 8 years) were examined. As a parameter of cerebral hemodynamics the mean and the peak blood flow velocity (mCBFV(MCA), pCBFV(MCA)) in the middle cerebral artery (MCA) were recorded by transcranial Doppler sonography. At the same time the noninvasive blood pressure (Penaz method) and the CO(2) expiration concentration were investigated on 8 volunteers of the collective. As cerebral metabolic parameters we examined in 4 volunteers additionally the cerebral respiratory chain enzyme cytochrome aa3 (ccytaa3) and the cerebral oxygen saturation (cHbO(2)) by the transcranial near infrared spectroscopy. With each volunteer 4 measurement series were carried out with a special active and passive exercise program for the right upper as well as the right lower extremity. Each measurement series was formed according to the evoked flow test (R. Aaslid): Exercises were carried out for 20 s, followed by a break of 20 s; this was repeated 10 times for each series. RESULTS: During active exercises of the right lower extremity we found an increase of 13.6% (p < 0.001) of pCBFV(MCA) and an increase of 3.8% (p = 0.003) of mCBFV(MCA). During passive exercises of the lower extremity the increases ran up to 12.3% (p < 0.001) for pCBFV(MCA) and 3.4% (p = 0.004) for mCBFV(MCA). The increases of pCBFV(MCA) came up to 12.5% (p < 0.001) at active exercises of the right upper extremity, those of mCBFV(MCA) to 3.5% (p = 0.15). During passive exercises of the upper extremity the pCBFV(MCA) increased by 12.2% (p < 0.001) and the mCBFV(MCA) by 4.6% (p = 0.007). Significant increases of ccytaa3 were measured during active exercises of the upper extremity (1.6%; p = 0.04) and of the lower extremity (2.7%, p = 0.007). We also found an increase of ccytaa3 during passive exercises of the upper extremity (1.5%, p = 0.04). Significant changes of cHbO(2) were measured with 2.5% (p < 0.05) at active exercises of the lower extremity. CONCLUSION: These studies show that active as well as passive clinical exercises cause an increase of cerebral blood flow velocity. We attribute the increase of cerebral hemodynamics and cerebral metabolism to cerebral activation and autoregulative mechanisms.