Cerebrovascular and cardiovascular responses to the Valsalva manoeuvre during hyperthermia.

BACKGROUND: During hyperthermia, the perturbations in mean arterial blood pressure (MAP) produced by the Valsalva manoeuvre (VM) are more severe. However, whether these more severe VM-induced changes in MAP are translated to the cerebral circulation during hyperthermia is unclear. METHODS: Healthy participants (n = 12, 1 female, mean ± SD: age 24 ± 3 years) completed a 30 mmHg (mouth pressure) VM for 15 s whilst supine during normothermia and mild hyperthermia. Hyperthermia was induced passively using a liquid conditioning garment with core temperature measured via ingested temperature sensor. Middle cerebral artery blood velocity (MCAv) and MAP were recorded continuously during and post-VM. Tieck's autoregulatory index was calculated from the VM responses, with pulsatility index, an index of pulse velocity (pulse time) and mean MCAv (MCAvmean ) also calculated. RESULTS: Passive heating significantly raised core temperature from baseline (37.9 ± 0.2 vs. 37.1 ± 0.1°C at rest, p < 0.01). MAP during phases I through III of the VM was lower during hyperthermia (interaction effect p < 0.01). Although an interaction effect was observed for MCAvmean (p = 0.02), post-hoc differences indicated only phase IIa was lower during hyperthermia (55 ± 12 vs. 49.3 ± 8 cm s- 1 for normothermia and hyperthermia, respectively, p = 0.03). Pulsatility index was increased 1-min post-VM in both conditions (0.71 ± 0.11 vs. 0.76 ± 0.11 for pre- and post-VM during normothermia, respectively, p = 0.02, and 0.86 ± 0.11 vs. 0.99 ± 0.09 for hyperthermia p < 0.01), although for pulse time only main effects of time (p < 0.01), and condition (p < 0.01) were apparent. CONCLUSION: These data indicate that the cerebrovascular response to the VM is largely unchanged by mild hyperthermia.

Fetal Middle Cerebral Artery Pulsatility Index in No-Risk Pregnancies: Effects of Auditory Stimulation and Pregnancy Order.

Pulsatility index (PI) values in a fetal middle cerebral artery (MCA) were compared in no-risk pregnancies to examine the differences related to auditory stimulation test and pregnancy order. The study included 196 women with no-risk pregnancies selected from the database of more than 1000 pregnant women divided into two groups. Group 1 consisted of 98 nulliparous women (C1 = 98) and Group 2 consisted of 98 parous women (C2 = 98). All pregnant women were of comparable age and fetal gestational age (GA) when MCA-PI values were recorded. Measurements of PI values in fetal MCA were obtained before and immediately after the application of fetal auditory stimulation test. The MCA-PI measuring was conducted in the period between the 36th and the 41st week of GA. The results showed that PI baseline values and PI values after defined auditory stimulation were significantly different when measured in nulliparous women compared to parous women (p = 0.001; p = 0.003, respectively), while no group differences were observed in relative PI value changes due to auditory stimulation. These findings suggest that hemodynamic changes in fetal MCA caused by defined auditory stimulation measured by PI value changes may be valuable in the assessment of fetal auditory perception functionality and its development.

An effect of maternal nifedipine therapy on fetoplacental blood flow: a prospective study.

PURPOSE: The aim of this study is to assess the effects of maternal nifedipine administration on placental and fetal blood flow. METHODS: A total of 29 patients with preterm labor diagnosis admitted to the tertiary care center, Zeynep Kamil Hospital, were evaluated. Before and 24-48 h after administration of oral nifedipine, Doppler ultrasound scan was carried out to measure fetal middle cerebral artery, ductus venosus, umbilical artery, and maternal uterine artery blood flow. RESULTS: After 24 and 48 h of therapy, there were no changes in mean PI and RI in the umbilical arteries and ductus venosus (p > 0.05). Fetal middle cerebral artery and maternal uterine artery PI and RI values showed a significant reduction 24-48 h after oral nifedipine therapy (p < 0.05). CONCLUSIONS: Our study showed that 24 and 48 h after oral nifedipine therapy, there is a significant increase in fetal MCA and maternal uterine artery blood flow, while fetal umbilical artery and ductus venosus Doppler values do not change.

The effects of transcranial LED therapy (TCLT) on cerebral blood flow in the elderly women.

During aging processes, there is a range of functional changes, where we can highlight the disease related to the central nervous system, such as Alzheimer disease and others forms of dementia. This study investigated the effects of transcranial light emitting diode (LED) on cerebral blood flow in healthy elderly women analyzed by transcranial Doppler ultrasound (TCD) of the right and left middle cerebral artery and basilar artery. Twenty-five noninstitutionalized elderly women (mean age 72 years old), with a cognitive status >24, were assessed using transcranial Doppler ultrasound on two separate occasions: pre-irradiation and post-transcranial LED therapy (TCLT). Prior to this, they answered two questionnaires: the perceived stress scale and the general health questionnaire. TCLT (627 nm, 70 mW/cm(2), 10 J/cm(2)) was performed at four points of the frontal and parietal region for 30 s each, totaling 120 s two times per week for 4 weeks. Paired t-test results showed that there was a significant improvement after TCLT with increase in the systolic and diastolic velocity of the left middle cerebral artery (25 and 30%, respectively) and basilar artery (up to 17 and 25%), as well as a decrease in the pulsatility index and resistance index values of the three cerebral arteries analyzed (p < 0.05). TCD parameters showed improvement in the blood flow on the arteries analyzed. TCLT promoted a blood and vasomotor behavior of the basilar and middle cerebral arteries in healthy elderly women.

Efficacy and safety of MLC601 (NeuroAiD®), a traditional Chinese medicine, in poststroke recovery: a systematic review.

BACKGROUND: Subsequent to a pooled analysis of 2 trials, several more studies have been published assessing the benefit of MLC601 in stroke patients. Hence, it is timely to conduct an updated meta-analysis to frame the interpretation of the results of an ongoing large multicenter, randomized, double-blind, placebo-controlled study. Therefore, we conducted a systematic review of the efficacy of MLC601 in improving the recovery of stroke patients. METHODS: PubMed® and the Cochrane Library® databases were searched for trials evaluating MLC601 in stroke patients. Primary outcome was functional independence, assessed by the Barthel Index or the Diagnostic Therapeutic Effects of Apoplexy scoring system, item 8. Secondary outcomes were improvement in functional independence scores, motor recovery, reduction in visual field defect and increase in cerebral blood flow. Two authors performed the article selection, appraisal and data extraction while resolving differences through discussion or consulting a third author. Data were analyzed in RevMan5®. Meta-analysis was conducted using a random effects model. RESULTS: This review included 6 studies with overall low risk of bias but some clinical heterogeneity. MLC601 increased the chances of achieving functional independence after stroke compared to control treatments (risk ratio, 2.35; 95% CI, 1.31-4.23). No deaths and 4 serious adverse events were reported in the MLC601 group, although detail was sparse with inconsistent reporting. CONCLUSIONS: There is evidence that MLC601 as an add-on to standard treatment could be effective in improving functional independence and motor recovery and is safe for patients with primarily nonacute stable stroke.

Acute volume expansion attenuates hyperthermia-induced reductions in cerebral perfusion during simulated hemorrhage.

Hyperthermia reduces the capacity to withstand a simulated hemorrhagic challenge, but volume loading preserves this capacity. This study tested the hypotheses that acute volume expansion during hyperthermia increases cerebral perfusion and attenuates reductions in cerebral perfusion during a simulated hemorrhagic challenge induced by lower-body negative pressure (LBNP). Eight healthy young male subjects underwent a supine baseline period (pre-LBNP), followed by 15- and 30-mmHg LBNP while normothermic, hyperthermic (increased pulmonary artery blood temperature ~1.1°C), and following acute volume infusion while hyperthermic. Primary dependent variables were mean middle cerebral artery blood velocity (MCAvmean), serving as an index of cerebral perfusion; mean arterial pressure (MAP); and cardiac output (thermodilution). During baseline, hyperthermia reduced MCAvmean (P = 0.001) by 12 ± 9% relative to normothermia. Volume infusion while hyperthermic increased cardiac output by 2.8 ± 1.4 l/min (P < 0.001), but did not alter MCAvmean (P = 0.99) or MAP (P = 0.39) compared with hyperthermia alone. Relative to hyperthermia, at 30-mmHg LBNP acute volume infusion attenuated reductions (P < 0.001) in cardiac output (by 2.5 ± 0.9 l/min; P < 0.001), MAP (by 5 ± 6 mmHg; P = 0.004), and MCAvmean (by 12 ± 13%; P = 0.002). These data indicate that acute volume expansion does not reverse hyperthermia-induced reductions in cerebral perfusion pre-LBNP, but that it does attenuate reductions in cerebral perfusion during simulated hemorrhage in hyperthermic humans.

Self-regulation of cerebral blood flow by means of transcranial Doppler sonography biofeedback.

BACKGROUND: Transcranial Doppler sonography (TCD) allows the continuous non-invasive assessment of intracranial blood flow velocities with high temporal resolution. It may therefore prove suitable for biofeedback of cerebral perfusion. PURPOSE: The study explored whether healthy individuals can successfully be trained in self-regulation of cerebral blood flow using TCD biofeedback. METHODS: Twenty-two subjects received visual feedback of flow velocities in the middle cerebral arteries of both hemispheres. They were randomly assigned to two groups, one of which attempted to increase, the other to decrease the signal within eight training sessions. Heart rate and respiratory frequency were also monitored. RESULTS: Both groups achieved significant changes in flow velocities in the expected directions. Modulations in heart rate and respiratory frequency during biofeedback did not account for these effects. CONCLUSIONS: TCD biofeedback enables efficient self-regulation of cerebral blood flow. It is promising in applications such as the treatment of migraine and post-stroke rehabilitation.

The effects of sevoflurane on cerebral blood flow autoregulation and flow-metabolism coupling during cardiopulmonary bypass.

BACKGROUND: previous studies on non-cardiac surgical patients have shown that cerebral pressure-flow autoregulation and cerebral flow-metabolism coupling are maintained with sevoflurane. The effects of sevoflurane on cerebral blood flow (CBF) autoregulation and flow-metabolism coupling during cardiopulmonary bypass (CPB) have not been studied previously. METHODS: the effects of sevoflurane-induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE) and flow autoregulation, were studied in 16 patients undergoing cardiac surgery. The experimental procedure was performed during non-pulsatile CPB with mild hypothermia (34 degreesC) in fentanyl/droperidol-anesthetized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation and jugular venous pressure were measured continuously. Autoregulation was tested during changes in the mean arterial pressure (40-90 mmHg), induced by sodium nitroprusside and norepinephrine before (control), and during additional sevoflurane administration, in a dose that resulted in an EEG burst-suppression level of 4-6/min. RESULTS: sevoflurane, at an inspired concentration of 3.36 ± 0.03%, induced a 17% decrease in CBFV (P<0.05) and a 22% decrease in COE (P<0.05) compared with the control. The slope of the positive relationship between CBFV and cerebral perfusion pressure was steeper with sevoflurane (p<0.01) compared with control measurements, as was the slope of the negative relationship between cpp and coe (p<0.01). CONCLUSION: burst-suppression doses of sevoflurane exert an intrinsic cerebral vasodilatory effect, which impairs CBF autoregulation during mildly hypothermic CPB. Furthermore, during sevoflurane administration, CBF is in excess relative to oxygen demand, indicating a partial loss of the cerebral flow-metabolism coupling.

Effects of early hyperbaric oxygen therapy on clinical outcome in postoperative patients with intracranial aneurysm.

OBJECTIVE: To investigate the effects of hyperbaric oxygen (HBO2) in postoperative patients with intracranial aneurysm. METHODS: A total of 120 patients who underwent clipping of intracranial aneurysm of the anterior circulation were randomized into the HBO2 group (n = 60) or the Control group (n = 60). Compared with the Control group, patients in the HBO2 group received additional HBO2 therapy, which was initiated within one to three days as soon as they were deemed clinically stable, for at least 20 sessions (one session per day). Mean flow velocities of the middle cerebral artery (MCA) on the operative approach side were measured on Days 1, 3, 7, 14 and 21 after operation. CT scans were performed on Days 1, 7, 14 and 21 after surgery to determine the abnormal density volume in the operative area. Cases associated with symptomatic cerebral vasospasm (CVS) were assessed on Days 3, 7 as well as 14, and the functional state determined by Karnofsky Performance Scale (KPS) score was evaluated on Days 3 and 21 after operation. Finally, Glasgow Outcome Scale (GOS) scores were obtained at six months after surgery. RESULTS: There were no differences between groups in terms of the mean flow velocities of MCA on the operative approach side, the cases with symptomatic CVS, and the KPS scores within three days after surgery (P > 0.05). Compared with those of the Control group, the mean flow velocities of MCA on the operative approach side were significantly lower in the HBO2 group on Days 7 and 14 (P < 0.05 or P < 0.01). On Days 7, 14 and 21, patients in the HBO2 group had smaller HBO2 density volume in the operative region than those in the Control group (P < 0.05). The HBO2 group developed less cases of symptomatic CVS than the Control group did on Days 7 (chi2 = 4.04, P < 0.05) and 14 (chi2 = 4.18, P < 0.05). The KPS scores were higher on Day 21 after surgery in the HBO2 group (P < 0.05). More patients in the HBO2 group achieved GOS scores of 4 and 5 at six months after surgery (chi2 = 6.032, P < 0.05). CONCLUSIONS: Early HBO2 appears to be beneficial asan adjunctive treatment of postoperative intracranial aneurysm. Attenuating postoperative CVS, brain edema, and cerebral ischemia contributes to the effectiveness of HBO2.

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.

Changes in Doppler blood flow velocity in middle cerebral artery in response to airborne sound in low- and high-risk human fetuses.

OBJECTIVE: To examine fetal auditory perception in low- and high-risk pregnancies in period from 27 to 31 weeks gestational age with the aim to establish diagnostic parameters in prenatal detection of the degree of hearing development in a fetus. METHODS: Method of prenatal hearing screening was applied on 80 women divided in two groups: Control group (C=22), consisted of pregnant women with low-risk pregnancies, and Experimental group (E=58), consisted of pregnant women with high-risk pregnancies (pregnancies with diagnosis of: preterm delivery, hypertension and/or intrauterine growth restriction (IUGR), diabetes). PHS was applied in period from 27 to 31 weeks gestational age. Brain circulation changes in fetal middle cerebral artery (MCA) caused by defined sound stimulus, as the indicator of fetal auditory reactions, were registered on Doppler ultrasound apparatus. After visualization of MCA, a sound stimulus was delivered. The stimulus consisted of one defined sound which is a digitally produced sound with the intensity of 90 dB, frequency range of 1500-4500 Hz, and duration of 0.2s (click) and it was presented only once. Measurements in observed artery were taken before (baseline) and after defined sound stimulation. RESULTS: Results showed that the absolute and relative difference in Pulsatility index (baseline and after sound stimulation) were greater for the high-risk group compared to the low-risk group (absolute difference: mean=0.36 vs mean=0.36) (relative difference: mean = ∼ 18% vs mean = ∼ 12%). When the low-risk group and the three high-risk group mean pairs were compared using multiple t-test, the diabetic group differed from the low-risk and two other high-risk groups; the low-risk and the two other high-risk groups did not differ from each other. Fetuses from pregnancies with diagnosis of diabetes demonstrated the most expressive reactibility and significantly higher absolute and relative changes of Pi values (absolute difference: mean=0.54, relative difference: mean=25.49%). CONCLUSION: The values of Pulsatility index (Pi) registered by PHS in low- and high-risk pregnancies may be used as differential and diagnostic parameters in fetal auditory perception examination. Fetuses from pregnancies with diagnosis of diabetes demonstrated significantly higher absolute and relative changes of Pi values compared to other groups of examined fetuses.

The effect of fetal heart rate on the peak systolic velocity of the fetal middle cerebral artery.

OBJECTIVE: To estimate the effect of an increase in the basal heart rate of the fetus on the middle cerebral artery peak systolic velocity (MCA-PSV). METHODS: This was a prospective longitudinal cohort. Patients between 14 and 36 weeks of gestation were enrolled (N=66). Ultrasound examinations were performed monthly. MCA-PSV measurements were assessed at 0-degree angle of insonation at basal fetal heart rate and after application of vibroacoustic stimulation. RESULTS: A total of 514 MCA-PSV measurements were obtained in 66 fetuses. No difference in fetal heart rate before and after vibroacoustic stimulation was noted before 27 weeks of gestation. A significant increase in fetal heart rate after vibroacoustic stimulation was detected from a mean+/-standard deviation gestational age of 27.1+/-1.3 weeks onward. A significant decrease in the MCA-PSV was noted between before vibroacoustic stimulation and after vibroacoustic stimulation measurements for examinations 3,4, and 5 (P<.001 for all). CONCLUSION: Acceleration of the fetal heart rate in the third trimester is associated with a decrease in the middle cerebral artery peak systolic velocity. Assessment of the MCA-PSV for the detection of fetal anemia, particularly in the third trimester, should be undertaken during a period of baseline fetal heart rate to avoid the potential of a false-negative result. LEVEL OF EVIDENCE: II.

Management of anti-Jka alloimmunization.

OBJECTIVE: To determine whether prenatal management using guidelines established for anti-D is applicable to anti-Jka. STUDY DESIGN: A computerized database containing the records of all alloimmunized pregnancies at The Ohio State University Medical Center with due dates from 1959 to 2008 was used to identify pregnancies affected only by anti-Jka. Only cases with evidence that the newborn was Jka antigen positive were included. RESULTS: Twenty affected pregnancies met inclusion criteria. Of those, 16 pregnancies required monitoring with serum titers only and 4 were followed with more diagnostic tests as recommended during that time period. One pregnancy with the highest titer of 32 and elevated middle cerebral artery peak systolic velocity (MCA PSV) required 4 intrauterine transfusions for fetal anemia. Another pregnancy with a titer of 32 had an infant who required phototherapy for hemolytic disease of the fetus/newborn (HDFN), with a hemoglobin value of 15.9 g/dL. None of the other 18 infants required any therapy for HDFN. CONCLUSION: Our case series identified severe disease in 1 of 20 pregnancies from anti-Jka using maternal antibody titer and MCA PSV. Criteria used for monitoring RhD alloimmunization were effective in detecting severe HDFN resulting from to anti-Jka.

Direct regulation of BK channels by phosphatidylinositol 4,5-bisphosphate as a novel signaling pathway.

Large conductance, calcium- and voltage-gated potassium (BK) channels are ubiquitous and critical for neuronal function, immunity, and smooth muscle contractility. BK channels are thought to be regulated by phosphatidylinositol 4,5-bisphosphate (PIP(2)) only through phospholipase C (PLC)-generated PIP(2) metabolites that target Ca(2+) stores and protein kinase C and, eventually, the BK channel. Here, we report that PIP(2) activates BK channels independently of PIP(2) metabolites. PIP(2) enhances Ca(2+)-driven gating and alters both open and closed channel distributions without affecting voltage gating and unitary conductance. Recovery from activation was strongly dependent on PIP(2) acyl chain length, with channels exposed to water-soluble diC4 and diC8 showing much faster recovery than those exposed to PIP(2) (diC16). The PIP(2)-channel interaction requires negative charge and the inositol moiety in the phospholipid headgroup, and the sequence RKK in the S6-S7 cytosolic linker of the BK channel-forming (cbv1) subunit. PIP(2)-induced activation is drastically potentiated by accessory beta(1) (but not beta(4)) channel subunits. Moreover, PIP(2) robustly activates BK channels in vascular myocytes, where beta(1) subunits are abundantly expressed, but not in skeletal myocytes, where these subunits are barely detectable. These data demonstrate that the final PIP(2) effect is determined by channel accessory subunits, and such mechanism is subunit specific. In HEK293 cells, cotransfection of cbv1+beta(1) and PI4-kinaseIIalpha robustly activates BK channels, suggesting a role for endogenous PIP(2) in modulating channel activity. Indeed, in membrane patches excised from vascular myocytes, BK channel activity runs down and Mg-ATP recovers it, this recovery being abolished by PIP(2) antibodies applied to the cytosolic membrane surface. Moreover, in intact arterial myocytes under physiological conditions, PLC inhibition on top of blockade of downstream signaling leads to drastic BK channel activation. Finally, pharmacological treatment that raises PIP(2) levels and activates BK channels dilates de-endothelized arteries that regulate cerebral blood flow. These data indicate that endogenous PIP(2) directly activates vascular myocyte BK channels to control vascular tone.

Time-locked association between rapid cerebral blood flow modulation and attentional performance.

OBJECTIVE: The study investigated relationships between rapid cerebral hemodynamic modulation and attentional performance. Based on former results on complex cognitive functioning, a specific association between the first seconds of the hemodynamic response and performance was hypothesized. METHODS: Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 48 healthy subjects. The applied task comprised motor reactions on a visual stimulus which was preceded by an acoustic warning signal (interstimulus interval 5s). Task-induced hemodynamic changes were assessed second-by-second, and related to reaction time using analysis of variance and linear regression. RESULTS: A right dominant blood flow response was observed. Flow velocity increase in the middle fraction of the interstimulus interval, i.e. seconds 2 and 3 after the cuing signal, significantly correlated with reaction time. This was not the case for the very early and late components of the response. CONCLUSIONS: The results suggest a time-locked association between cerebral blood flow increase and attentional performance. This is in accordance with neurophysiological studies that revealed the closest relationship between brain perfusion and cortical activity during a similar time window. SIGNIFICANCE: The study supports the assumption of a specific, relatively early time interval in which relationships between cerebral blood flow and behavior become apparent.

Coaccumulation of calcium and beta-amyloid in the thalamus after transient middle cerebral artery occlusion in rats.

Transient occlusion of the middle cerebral artery (MCAO) in rats leads to abnormal accumulation of beta-amyloid (Abeta) peptides in the thalamus. This study investigated the chemical composition of these deposits. Adult male human beta-amyloid precursor protein (APP) overexpressing (hAPP695) rats and their wild-type littermates were subjected to transient MCAO for 2 h or sham operation. After 26-week survival time, histological examination revealed an overlapping distribution pattern for rodent and human Abeta in the thalamus of hAPP695 rats subjected to MCAO. X-ray microanalysis showed that the deposits did not contain significant amount of iron, zinc, or copper typical to senile plaques. In contrast, the deposit both in hAPP695 and non-transgenic rats contained calcium and phosphorus in a ratio (1.28+/-0.15) characteristic to hydroxyapatites. Alizarin red staining confirmed that calcium coaccumulated in these Abeta deposits. It is suggested that APP expression is induced by ischemic insult in cortical neurons adjacent to infarct, which in turn is reflected as increased release of Abeta peptides by their corticothalamic axon endings. This together with insufficient clearance or atypical degradation of Abeta peptides lead to dysregulation of calcium homeostatis and coaccumulation in the thalamus.

Physiological and pathological observations on rat middle cerebral arteries and human AVM tissue cultures following single high-dose gamma irradiation.

In vitro isometric myograph and histopathological studies were performed on rat middle cerebral arteries (MCAs) to explore changes in contractile capacity following experimental Gamma Knife radiosurgery. Right MCAs were treated with 25 Gy and 50 Gy at the 50% isodose line, while contralateral vessels received 15 Gy and 20 Gy at the 20% isodose region. Survival period varied from 3 to 18 months. Reduction in contractile capacity of irradiated normal rat MCAs was detected but their lumina remained patent. In another study, we investigated human AVM tissue cultures in order to detect genetic and phenotypic modifications contributing to vessel occlusion after irradiation. In culture, the proliferation index decreased considerably following 15-, 20-, 25- or 50-Gy irradiation at the 5th posttreatment day and remained depressed during the observation period of 14 days. P53, p21Waf-1 and mdm-2 mRNA contents were elevated significantly after irradiation, indicating enhanced apoptosis. Immunohistochemistry revealed vigorous vimentin positivity in the nonirradiated control AVM cultures, which gradually decreased by the time in the irradiated specimens. Smooth muscle alpha-actin positivity was prominent in the irradiated cultivated samples, suggesting transformation of resting fibroblasts onto activated myofibroblastic elements with contractile capacity. This transformation process was confirmed by the appearance of TGF-Beta in the irradiated AVM cell lines also. These data support the hypothesis that one of the contributing factors to AVM shrinkage and obliteration after radiosurgery might be fibrocyte-myofibroblastic cell transformation in the vessel wall.

Effects of oral L-arginine on the foetal condition and neonatal outcome in preeclampsia: a preliminary report.

Estimation of the influence of oral supplementation with low dose of L-arginine on biophysical profile, foeto-placental circulation and neonatal outcome in preeclampsia. Randomized, placebo-controlled, double-blind, clinical trial. Oral therapy with 3 g of L-arginine daily or placebo as a supplement to standard therapy. Eighty-three preeclamptic women, randomly assigned to the L-arginine (n=42) or placebo (n=41) groups; [n=30 (L-arginine) and n=31 (placebo) ended the study, respectively]. Foetal gain chances due to ultrasound biometry, biophysical profile, Doppler velocimetry of pulsatility indices of umbilical and middle cerebral arteries, cerebro-placental ratio, as well as differences in duration of pregnancy and clinical data of newborn. L-arginine treatment transitory accelerated foetal gain and improved biophysical profile. Starting from 3rd week of therapy, the umbilical artery pulsatility indices values were significantly lower in L-arginine than in placebo group. Moreover, treatment with L-arginine caused significant increase of middle cerebral artery pulsatility indices and cerebro-placental ratio values. Latency was longer in L-arginine group. Neonates delivered in the L-arginine group revealed higher Apgar score. Supplementary treatment with oral L-arginine seems to be promising in improving foetal well-being and neonatal outcome as well as in prolonging pregnancy complicated with preeclampsia. However, these benefits require confirmation in more-powered, larger studies.

Effect of magnesium, high altitude and acute mountain sickness on blood flow velocity in the middle cerebral artery.

Cerebral blood flow is thought to increase at high altitude and in subjects suffering from acute mountain sickness (AMS); however, data from the literature are contentious. Blood flow velocity in the middle cerebral artery (MCAv) may be used as a proxy measure of cerebral blood flow. Using transcranial Doppler sonography, MCAv was measured during normo- and hyper-ventilation in subjects who participated in a trial that tested the effect of magnesium supplementation on the prevention of AMS. First, MCAv was recorded at 353 m (baseline). Subjects were then randomized to receive oral magnesium citrate and matching placebo. A second measurement was taken after a 24 +/- 2 h ascent from 1130 m to 4559 m (altitude I), and a third after a 20-24 h stay at 4559 m (altitude II). Using multivariate linear regression, an association was sought between MCAv and magnesium supplementation, subjects' age and gender, altitude itself, a temporary stay at altitude, and the presence of AMS (Lake Louise Score >6 with ataxia, nausea and/or headache). Subjects with AMS had additional Doppler recordings immediately before and after rescue medication (oxygen, dexamethasone and acetazolamide). Forty-seven subjects had measurements at baseline, 39 (21 receiving magnesium and 18 placebo) at altitude I and 26 (13 receiving magnesium and 13 placebo) at altitude II. During hyperventilation, MCAv decreased consistently (for each measurement, P<0.001). Magnesium significantly increased MCAv by 8.4 cm.s(-1) (95% confidence interval, 1.8-15), but did not prevent AMS. No other factors were associated with MCAv. Eleven subjects had severe AMS [median score (range), 11 (8-16)] and, after rescue medication, the median score decreased to 3 (range, 0-5; P=0.001), but MCAv remained unchanged (65 +/- 18 cm.s(-1) before compared with 67 +/- 16 cm.s(-1) after rescue medication; P=0.79). MCAv was increased in subjects who received magnesium, but was not affected by exposure to high altitude or by severe AMS.

Effect of taurine in combination with electroacupuncture on neuronal damage following transient focal cerebral ischemia in rats.

The present study was to investigate whether taurine is beneficial to the neuroprotective effects of electroacupuncture (EA) on rat cerebral ischemia induced by transient Middle Cerebral Artery Occlusion (MCAO). Histological change and DNA damage degree were detected by H&E staining and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) method. Taurine and EA combination group could significantly decrease the percentages of infarct area and cell loss induced by ischemic injury in the striatum (p<0.05, vs singly treated with taurine or EA), and also the percentage of TUNEL-positive cells was smaller than both singly treated groups (p<0.05). Moreover, immunoreactivities detection of Bcl-2 (which promotes cell survival), Bax (which promotes cell death) and P53 (product of tumor suppressor gene p53) showed that the combination group apparently attenuated P53 immunoreactivities expression whereas augmented the immunoreactivities expression ratio of Bcl-2 to Bax in cortex. These results suggested that combining use of taurine and EA could exert better neuroprotective effects, which might be related to the regulation of apoptosis pathway.