scholarly journals Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain

2021 ◽  
Vol 43 (1) ◽  
pp. 301-312
Author(s):  
Philippe Bonnin ◽  
Tania Vitalis ◽  
Leslie Schwendimann ◽  
Alexandre Boutigny ◽  
Nassim Mohamedi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Mouse Brain ◽  
Somatostatin Receptor ◽  
Neurovascular Unit ◽  
Neonatal Mouse ◽  
Tissue Loss ◽  
Polymerase Inhibitor ◽  
Blood Flow Velocities ◽  
Neonatal Ischemia ◽  
The Right

The poly(ADP-ribose) polymerase inhibitor PJ34 has recently been reported to increase cerebral blood flow, via the endothelial NO synthase, in the naive mouse brain throughout life. We addressed here the benefits of PJ34 after neonatal ischemia on hemodynamics and components of the neurovascular unit including the blood-brain barrier (BBB), microglia, and astrocytes. Nine-day-old mice were subjected to permanent MCA occlusion (pMCAo), and treated with either PBS or PJ34 (10 mg/kg). Mean blood-flow velocities (mBFV) were measured in both internal carotid arteries (ICA) and basilar trunk (BT) using Doppler-ultrasonography. BBB opening was assessed through somatostatin-receptor type-2 internalization and immunohistochemistry at 24 and 48 h. Lesion areas were measured 8 days after ischemia. In PBS-treated mice, pMCAo involved a drop in mBFV in the left ICA (p < 0.001 vs. basal), whereas mBFV remained stable in both right ICA and BT. PJ34 prevented this drop in the left ICA (NS vs. basal) and increased mBFV in the right ICA (p = 0.0038 vs. basal). No modification was observed in the BT. In contrast to PBS, BBB disruption extent and astrocyte demise were reduced in PJ34 mice only in the rostral brain at 48 h and 8 days post-pMCAo, respectively. Accordingly, 8 days after pMCAo, affected areas were reduced in the rostral brain (Bregma +0.86 and +0.14 mm), whereas total tissue loss was not reduced after PJ34 (4.0 ± 3.1%) vs. PBS (5.8 ± 3.4%). These results show that PJ34 reduced BBB permeability, astrocyte demise, and tissue loss (particularly in the rostral territories), suggesting that collateral supply mainly proceeds from the anterior ICA’s branches in the ischemic neonatal mouse brain.

Blood Flow Velocity Profiles in Pulmonary Branch Arteries in Lambs

1995 ◽  
Vol 117 (2) ◽  
pp. 237-241
Author(s):  
H. Katayama ◽  
G. W. Henry ◽  
C. L. Lucas ◽  
B. Ha ◽  
J. I. Ferreiro ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Maximum Velocity ◽  
Left Pulmonary Artery ◽  
Control Group ◽  
Pulsed Doppler Ultrasound ◽  
Right Pulmonary Artery ◽  
Blood Flow Velocities ◽  
The Right

We studied the detailed profiles of blood flow in the right and left pulmonary arteries using 20 MHz pulsed Doppler ultrasound equipment in a lamb model. Fourteen lambs aged four to six weeks were selected. In six lambs, monocrotaline pyrrole was injected parenterally to create pulmonary hypertension (PH group). Eight other lambs served as unaltered controls (control group). The blood flow velocities were sampled in 1mm increments along the anterior—posterior axis of the branch arteries. The maximum velocity of the forward flow in the left pulmonary artery was higher than that in the right pulmonary artery in the control group (71.7 ± 15.9cm/s vs 60.2 ± 13.5; p < 0.05). The fastest backward flow was located at the posterior position of the vessel in the right pulmonary artery in the control group. No significant bias in location was shown in the left pulmonary artery. Using indices of P90, acceleration time, P90*AcT, the velocity waveforms in the PH group were compared with those in the control group. In the left pulmonary artery, every index in the control group showed a significantly greater value that in the PH group. On the other hand, no significant differences were found between either group in the right pulmonary artery.

Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage

1995 ◽  
Vol 83 (1) ◽  
pp. 118-122 ◽  
Author(s):  
John K. B. Afshar ◽  
Ryszard M. Pluta ◽  
Robert J. Boock ◽  
B. Gregory Thompson ◽  
Edward H. Oldfield
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Primate Model ◽  
Content Type ◽  
Continuous Release ◽  
Blood Flow Velocities ◽  
The Right ◽  
Fine Print

✓ The continuous release of nitric oxide (NO) is required to maintain basal cerebrovascular tone. Oxyhemoglobin, a putative spasmogen, rapidly binds NO, implicating loss of NO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). If vasospasm is mediated by depletion of NO in the vessel wall, it should be reversible by replacement with NO. To investigate this hypothesis, the authors placed blood clots around the right middle cerebral artery (RMCA) of four cynomolgus monkeys; four unoperated animals served as controls. Arteriography was performed before and 7 days after surgery to assess the presence and degree of vasospasm, which was quantified in the anteroposterior (AP) projection by computerized image analysis. On Day 7, cortical cerebral blood flow (CBF) in the distribution of the right MCA was measured during four to six runs in the right internal carotid artery (ICA) of brief infusions of saline followed by NO solution. Arteriography was performed immediately after completing the final NO infusion in three of the four animals with vasospasm. Right MCA blood flow velocities were obtained using transcranial Doppler before, during, and after NO infusion in two vasospastic animals. After ICA NO infusion, arteriographic vasospasm resolved (mean percent of preoperative AP area, 55.9%); that is, the AP areas of the proximal portion of the right MCA returned to their preoperative values (mean 91.4%; range 88%–96%). Compared to ICA saline, during ICA NO infusion CBF increased 7% in control animals and 19% in vasospastic animals (p < 0.002) without significant changes in other physiological parameters. During NO infusion, peak systolic right MCA CBF velocity decreased (130 to 109 cm/sec and 116 to 76 cm/sec) in two vasospastic animals. The effects of ICA NO on CBF and CBF velocity disappeared shortly after terminating NO infusion. Intracarotid infusion of NO in a primate model of vasospasm 1) increases CBF, 2) decreases cerebral vascular resistance, 3) reverses arteriographic vasospasm, and 4) decreases CBF velocity in the vasospastic artery without producing systemic hypotension. These findings indicate the potential for the development of targeted therapy to reverse cerebral vasospasm after SAH.

scholarly journals Differences between the Filling Velocities of the Left and Right Heart Ventricle in Racing Pigeons (Columba Livia F. Domestica) and the Influence of Anesthesia with Isoflurane

2019 ◽  
Vol 6 (4) ◽  
pp. 79 ◽  
Author(s):  
Legler ◽  
Koy ◽  
Kummerfeld ◽  
Fehr
Keyword(s):  
Blood Flow ◽  
Left Ventricle ◽  
Columba Livia ◽  
Right Heart ◽  
Sonographic Examination ◽  
Blood Flow Velocities ◽  
Early Passive ◽  
The Right ◽  
Ventricular Filling ◽  
Flow Velocities

The ventricular filling velocities during diastole and the influence of isoflurane anesthesia on these blood flow velocities of the racing pigeon (n = 43) are evaluated by pulsed-wave (PW) Doppler sonography. Sonographic examination demonstrates an early passive ventricular (E wave) and late active (A wave) ventricular filling. The results indicate differences between the two heart ventricles. Especially, the E wave velocity of the right heart is significantly lower than in the left heart, which is explained by the crescent-shaped cavity of the right ventricle around the left ventricle. The faster active filling velocities are significantly influenced by heart rate in conscious birds. Anesthesia with isoflurane leads to a significant decrease of the diastolic blood flow velocities, and the A wave velocities of both ventricles are especially influenced. Anesthesia with isoflurane induces a high incidence of insufficiencies of the left atrioventricular valve in the preejection period. These observations indicate that a contraction of the left ventricle myocardium is important for a complete valvular closure and for normal functioning of this heart valve. The effective closure of the right atrioventricular muscle valve in anesthetized pigeons supports the observation of the fast innervation of this muscle valve via a direct connection to the right atrium.

scholarly journals Cerebral Vasodilator Property of Poly(ADP-Ribose) Polymerase Inhibitor (PJ34) in the Neonatal and Adult Mouse Is Mediated by the Nitric Oxide Pathway

2020 ◽  
Vol 21 (18) ◽  
pp. 6569
Author(s):  
Philippe Bonnin ◽  
Christiane Charriaut-Marlangue ◽  
Julien Pansiot ◽  
Alexandre Boutigny ◽  
Jean-Marie Launay ◽  
...  
Keyword(s):  
Blood Flow ◽  
Matched Control ◽  
Parp Inhibitor ◽  
Percentage Increase ◽  
Blood Flows ◽  
Pathway Activation ◽  
Polymerase Inhibitor ◽  
Flow Through ◽  
Blood Flow Velocities

The poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 has been reported to improve endothelial dysfunction in the peripheral system. We addressed the role of PJ34 on the vascular tone and vasoreactivity during development in the mouse brain. Blood flows were measured in the basilar trunk using ultrasonography. Cerebral vasoreactivity or vasodilation reserve was estimated as a percentage increase in mean blood flow velocities (mBFV) recorded under normoxia-hypercapnia in control and after PJ34 administration. Non-selective and selective eNOS and nNOS inhibitors were used to evaluate the role of NO-pathway into the hemodynamic effects of PJ34. PJ34 increased mBFVs from 15.8 ± 1.6 to 19.1 ± 1.9 cm/s (p = 0.0043) in neonatal, from 14.6 ± 1.4 to 16.1 ± 0.9 cm/s (p = 0.0049) in adult, and from 15.7 ± 1.7 to 17.5 ± 2.0 cm/s (p = 0.0024) in aged mice 48 h after administration. These PJ34 values were similar to those measured in age-matched control mice under normoxia-hypercapnia. This recruitment was mediated through the activation of constitutive NO synthases in both the neonatal (38.2 ± 6.7 nmol/min/mg protein) and adult (31.5 ± 4.4 nmol/min/mg protein) brain, as compared to age-matched control brain (6.9 ± 0.4 and 6.3 ± 0.7 nmol/min/mg protein), respectively. In addition, quite selective eNOS inhibitor was able to inhibit the recruitment. PJ34 by itself is able to increase cerebral blood flow through the NO-pathway activation at least over 48 h after a single administration.

Cerebrovascular response to normal pregnancy: a longitudinal study

2006 ◽  
Vol 290 (5) ◽  
pp. H1856-H1861 ◽  
Author(s):  
T. K. Bergersen ◽  
T. W. Hartgill ◽  
J. Pirhonen
Keyword(s):  
Blood Flow ◽  
Longitudinal Study ◽  
Cerebral Autoregulation ◽  
Pressor Response ◽  
Normal Pregnancy ◽  
Vasoconstrictor Response ◽  
Blood Flow Velocities ◽  
End Tidal ◽  
The Right ◽  
Flow Velocities

We used a longitudinal study design ( gestational weeks 8, 15, 22, 29, and 36 and 12 wk postpartum ) to investigate the effect of normal pregnancy on cerebral autoregulation and pressor response. Blood flow velocities in the right internal carotid artery, end-tidal CO2, and mean arterial pressure (MAP) were simultaneously and continuously recorded in 16 healthy pregnant women during standardized hyperventilation and handgrip. Blood flow velocities were recorded using Doppler ultrasound sampled beat by beat using the ECG signal. The results demonstrate that the vasoconstrictor response to hyperventilation is unchanged during pregnancy. During standardized handgrip, MAP showed a statistically significant increase during pregnancy that did not affect cerebral blood flow. A statistically significant reduction in the MAP response to handgrip was seen in week 36. In conclusion, pregnancy has no impact on cerebral autoregulation. There is an impact on the pressor response resulting in a blunted reaction at week 36, probably caused by a fall in the baroreflex set point.

Patterns of Cerebral Blood Flow and Systemic Hemodynamics During Arithmetic Processing

2008 ◽  
Vol 22 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Natalie Werner ◽  
Neval Kapan ◽  
Gustavo A. Reyes del Paso
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Time Course ◽  
Doppler Sonography ◽  
Transcranial Doppler Sonography ◽  
Systemic Hemodynamics ◽  
Heart Period ◽  
Blood Flow Velocities ◽  
Flow Velocities

The present study explored modulations in cerebral blood flow and systemic hemodynamics during the execution of a mental calculation task in 41 healthy subjects. Time course and lateralization of blood flow velocities in the medial cerebral arteries of both hemispheres were assessed using functional transcranial Doppler sonography. Indices of systemic hemodynamics were obtained using continuous blood pressure recordings. Doppler sonography revealed a biphasic left dominant rise in cerebral blood flow velocities during task execution. Systemic blood pressure increased, whereas heart period, heart period variability, and baroreflex sensitivity declined. Blood pressure and heart period proved predictive of the magnitude of the cerebral blood flow response, particularly of its initial component. Various physiological mechanisms may be assumed to be involved in cardiovascular adjustment to cognitive demands. While specific contributions of the sympathetic and parasympathetic systems may account for the observed pattern of systemic hemodynamics, flow metabolism coupling, fast neurogenic vasodilation, and cerebral autoregulation may be involved in mediating cerebral blood flow modulations. Furthermore, during conditions of high cardiovascular reactivity, systemic hemodynamic changes exert a marked influence on cerebral blood perfusion.

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