scholarly journals Dissociation between CSD-evoked metabolic perturbations and meningeal afferent activation and sensitization: implications for mechanisms of migraine headache onset

2017 ◽  
Author(s):  
Jun Zhao ◽  
Dan Levy
Keyword(s):  
Blood Flow ◽  
Migraine With Aura ◽  
Male Rats ◽  
Unit Recording ◽  
Cortical Blood Flow ◽  
Afferent Activation ◽  
Nociceptive Responses ◽  
Headache Onset ◽  
Meningeal Nociception ◽  
Large Vessels

AbstractThe onset of the headache phase during attacks of migraine with aura, which occur in about 30% of migraineurs, is believed to involve cortical spreading depression (CSD) and the ensuing activation and sensitization of primary afferent neurons that innervate the intracranial meninges, and their related large vessels. The mechanism by which CSD enhances the activity and mechanosensitivity of meningeal afferents remains poorly understood, but may involve cortical metabolic perturbations. We employed extracellular single-unit recording of meningeal afferent activity and monitored changes in cortical blood flow and tissue partial pressure of oxygen (tpO2) in anesthetized male rats to test whether the prolonged cortical hypoperfusion and reduction in tissue oxygenation that occur in the wake of CSD contribute to meningeal nociception. Suppression of CSD-evoked cortical hypoperfusion with the cyclooxygenase inhibitor naproxen blocked the reduction in cortical tpO2, but had no effect on the activation of meningeal afferents. Naproxen, however, distinctly prevented CSD-induced afferent mechanical sensitization. Counteracting the CSD-evoked persistent hypoperfusion and reduced tpO2 by preemptively increasing cortical blood flow using the K(ATP) channel opener levcromakalim did not inhibit the sensitization of meningeal afferents, but prevented their activation. Our data show that the cortical hypoperfusion and reduction in tpO2 that occur in the wake of CSD can be dissociated from the activation and mechanical sensitization of meningeal afferent responses suggesting that the metabolic changes do not contribute directly to these neuronal nociceptive responses.Significance statementCSD-evoked activation and mechanical sensitization of meningeal afferents is thought to mediate the headache phase in migraine with aura. We report that blocking the CSD-evoked cortical hypoperfusion and reduced tpO2 by cyclooxygenase inhibition is associated with the inhibition of the afferent sensitization but not their activation. Normalization of these CSD-evoked metabolic perturbations by activating K(ATP) channels is, however, associated with the inhibition of afferent activation but not sensitization. These results question the contribution of cortical metabolic perturbations to the triggering mechanism underlying meningeal nociception and the ensuing headache in migraine with aura, further point to distinct mechanisms underlying the activation and sensitization of meningeal afferents in migraine and highlight the need to target both processes for an effective migraine therapy.

scholarly journals The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K+ stimulation but not cortical spreading depression-induced afferent sensitization but not cortical spreading depression-induced afferent sensitization

2017 ◽  
Author(s):  
Jun Zhao ◽  
Dan Levy
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Fold Increase ◽  
Male Rats ◽  
Cgrp Receptor ◽  
Unit Recording ◽  
Afferent Activation ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonist ◽  
Afferent Response

AbstractIntroductionCortical spreading depression (CSD) is believed to promote migraine headache by enhancing the activity and mechanosensitivity of trigeminal intracranial meningeal afferents. One putative mechanism underlying this afferent response involves an acute excitation of meningeal afferents by cortical efflux of K+ and the ensuing antidromic release of pro-inflammatory sensory neuropeptides, such as calcitonin gene-related peptide (CGRP).ObjectivesWe sought to investigate whether (i) a brief meningeal K+ stimulus leads to CGRP-dependent enhancement of meningeal afferent responses, and (ii) CSD-induced meningeal afferent activation and sensitization involve CGRP receptor signaling.MethodsExtracellular single-unit recording were used to record the activity of meningeal afferents in anesthetized male rats. Stimulations included a brief meningeal application of K+ or induction of CSD in the frontal cortex using pinprick. CSD was documented by recording changes in cerebral blood flow using laser Doppler flowmetery. CGRP receptor activity was inhibited with BIBN4096 (333μM, i.v.).ResultsMeningeal K+ stimulation acutely activated 86% of the afferent tested and also promoted in ~65% of the afferents a 3-fold increase in ongoing activity which was delayed by 23.3±4.1 min and lasted for 22.2±5.6 min. K+ stimulation did not promote mechanical sensitization. Pretreatment with BIBN4096 suppressed the K+- induced delayed afferent activation, reduced CSD-evoked cortical hyperemia, but had no effect on the enhanced activation or mechanical sensitization of meningeal afferents following CSD.ConclusionWhile CGRP-mediated activation of meningeal afferents evoked by cortical efflux of K+ could promote headache, acute activation of CGRP receptors may not play a key role in mediating CSD-evoked headache.Previous presentation of the research, manuscript, or abstractParts of the manuscript have been presented previously only in an abstract form.

Effects of Ethanol on EEG and Cortical Blood Flow in the Cat

1968 ◽  
Vol 29 (4) ◽  
pp. 828-838 ◽  
Author(s):  
A. A. Hadji-Dimo ◽  
R. Ekberg ◽  
D. H. Ingvar
Keyword(s):  
Blood Flow ◽  
Cortical Blood Flow

scholarly journals Chinese Herbal Medicine Alleviates Thyroidectomy-Induced Cardiopulmonary Exercise Dysfunction in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Tai-Yuan Chuang ◽  
Chia-Ying Lien ◽  
Chih-Hsiang Hsu ◽  
Chen-Wen Lu ◽  
Chung-Hsin Wu
Keyword(s):  
Blood Flow ◽  
Body Weight ◽  
Negative Control ◽  
The Body ◽  
Male Rats ◽  
Free Triiodothyronine ◽  
Cardiopulmonary Exercise ◽  
Chinese Herbal ◽  
Subcutaneous Blood Flow ◽  
Tsh Levels

Hypothyroidism frequently causes cardiopulmonary dysfunction, such as heart failure and respiratory and metabolic deficiencies. This study investigated the effects of Chinese herbal formula B307 on thyroidectomy-induced cardiopulmonary exercise dysfunction in rats. Twenty male rats were equally divided into four groups: negative control with sham treatment, positive control with oral B307 treatment only, thyroidectomy treatment only, and thyroidectomy with B307 posttreatment groups. The feeding dose of B307 was 50 mg/kg per day for 14 days. We examined and then compared the thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4), and reactive oxygen species (ROS) from the blood of these four groups. Also, we compared the body weight, neck subcutaneous blood flow, cardiac ejection function, cardiopulmonary exercise function of oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ = VCO2/VO2) among the four groups. Our results indicated that thyroidectomized rats had significantly decreased body weight, neck subcutaneous blood flow, cardiac ejection function, serum T3 and T4, and VO2 and VCO2, but had significantly increased ROS and TSH levels and RQ values compared with sham rats (P<0.01–0.05). In addition, thyroidectomized rats receiving oral B307 treatment had significantly increased body weight, neck subcutaneous blood flow, cardiac ejection function, and VO2, but significantly decreased ROS and TSH levels and VCO2 and RQ values compared with thyroidectomized rats (P<0.01–0.05). We suggest that the B307 could be a protective and beneficial alternative treatment for thyroidectomy-induced cardiopulmonary exercise dysfunction.

scholarly journals Transcranial Doppler Evaluation of the Cerebral Vasculature in Women Patients who Have Migraine with Aura

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 3012-3017
Author(s):  
Igor Petrušić ◽  
Ana Podgorac ◽  
Aleksandra Radojičić ◽  
Jasna Zidverc-Trajković
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Migraine With Aura ◽  
Transcranial Doppler ◽  
Cerebral Blood Flow Velocity ◽  
Cerebral Arteries ◽  
Transcranial Doppler Sonography ◽  
Cerebrovascular Reactivity ◽  
Breath Holding ◽  
Left And Right

Abstract Background Previous studies suggest that increased cerebrovascular reactivity might be a feature of patients who have migraine with aura (MwA). The correlation between the clinical presentation of migraine with aura and transcranial Doppler parameters remains unclear. Objective The main aim of this study was to explore cerebral blood flow, vascular resistance, and cerebrovascular reactivity in women MwA. Also, the relationships between hemodynamic conditions and aura characteristics are examined. Design Cross-sectional study. Setting Headache Center, Neurology Clinic, Clinical Center of Serbia. Subjects Fifty-four women MwA and 49 healthy controls (HCs). Methods Transcranial Doppler sonography examination was used to determine blood flow mean velocity (MV) and pulsatility index (PI), as well as breath-holding index (BHI), in 15 arterial segments comprising the circle of Willis. Results A total of 54 women MwA and 49 HCs were studied. The PIs of all segments of the left and right middle cerebral arteries and the left and right anterior cerebral arteries were significantly higher in MwA with regards to HCs. Also, both the left and right BHIs were significantly higher in MwA than HCs. In addition, MVs of the right vertebral artery and the first segment of the basilar artery were significantly lower in MwA than HCs. Longer duration of migraine aura showed a weak negative correlation with the PI of the left posterior cerebral artery. Conclusions Our findings suggest increased vessel pulsatility, abnormal cerebrovascular reactivity, and decreased cerebral blood flow velocity in several arterial segments of the Willis circle in women MwA.

scholarly journals Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium

2011 ◽  
Vol 301 (3) ◽  
pp. R783-R790 ◽  
Author(s):  
Bradley J. Behnke ◽  
Robert B. Armstrong ◽  
Michael D. Delp
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Vascular Endothelium ◽  
Fold Increase ◽  
Male Rats ◽  
Type I ◽  
Fiber Types ◽  
Fast Twitch Muscle ◽  
Dose Responses ◽  
Fast Twitch

The influence of the sympathetic nervous system (SNS) upon vascular resistance is more profound in muscles comprised predominately of low-oxidative type IIB vs. high-oxidative type I fiber types. However, within muscles containing high-oxidative type IIA and IIX fibers, the role of the SNS on vasomotor tone is not well established. The purpose of this study was to examine the influence of sympathetic neural vasoconstrictor tone in muscles composed of different fiber types. In adult male rats, blood flow to the red and white portions of the gastrocnemius (GastRed and GastWhite, respectively) and the soleus muscle was measured pre- and postdenervation. Resistance arterioles from these muscles were removed, and dose responses to α1-phenylephrine or α2-clonidine adrenoreceptor agonists were determined with and without the vascular endothelium. Denervation resulted in a 2.7-fold increase in blood flow to the soleus and GastRed and an 8.7-fold increase in flow to the GastWhite. In isolated arterioles, α2-mediated vasoconstriction was greatest in GastWhite (∼50%) and less in GastRed (∼31%) and soleus (∼17%); differences among arterioles were abolished with the removal of the endothelium. There was greater sensitivity to α1-mediated vasoconstriction in the GastWhite and GastRed vs. the soleus, which was independent of whether the endothelium was present. These data indicate that 1) control of vascular resistance by the SNS in high-oxidative, fast-twitch muscle is intermediate to that of low-oxidative, fast-twitch and high-oxidative, slow-twitch muscles; and 2) the ability of the SNS to control blood flow to low-oxidative type IIB muscle appears to be mediated through postsynaptic α1- and α2-adrenoreceptors on the vascular smooth muscle.

Cortical Blood Flow and Negative Symptoms in Schizophrenia

1996 ◽  
Vol 33 (3) ◽  
pp. 127-131 ◽  
Author(s):  
Zvi Zemishlany ◽  
Gene E. Alexander ◽  
Isak Prohovnik ◽  
Ron G. Goldman ◽  
Sukdeb Mukherjee ◽  
...  
Keyword(s):  
Blood Flow ◽  
Negative Symptoms ◽  
Cortical Blood Flow

Music and cortical blood flow: A functional near-infrared spectroscopy (fNIRS) study.

2014 ◽  
Vol 7 (4) ◽  
pp. 545-550 ◽  
Author(s):  
Marcelo Bigliassi ◽  
Vinícius Barreto-Silva ◽  
Thiago Ferreira Dias Kanthack ◽  
Leandro Ricardo Altimari
Keyword(s):  
Blood Flow ◽  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Functional Near Infrared Spectroscopy ◽  
Cortical Blood Flow

Time course of hemodynamic changes in rats with healed severe myocardial infarction

1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Male Rats ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Functional Changes

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

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