scholarly journals Endocannabinoids in cerebrovascular regulation

2016 ◽  
Vol 310 (7) ◽  
pp. H785-H801 ◽  
Author(s):  
Zoltán Benyó ◽  
Éva Ruisanchez ◽  
Miriam Leszl-Ishiguro ◽  
Péter Sándor ◽  
Pál Pacher
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Transient Receptor Potential ◽  
Large Body ◽  
Blood Perfusion ◽  
Receptor Activation ◽  
Transient Receptor Potential Vanilloid ◽  
Cb2 Receptors

The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation.

Abstract 146: Transient Receptor Potential Vanilloid 1 (TRPV1) Channel Contributes to Cerebral Reperfusion after Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sung-Ha Hong ◽  
Sean P Marrelli
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Transient Receptor Potential ◽  
Laser Speckle ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Flow Measurements ◽  
Trpv1 Channels ◽  
Cerebral Microvasculature ◽  
Cerebral Reperfusion

Introduction: The TRPV1 channel is a non-selective ion channel that is activated by capsaicinoids, temperature (>43 °C), and multiple factors produced during inflammation or injury. At this time, there is very little reported regarding a role of this channel in regulation of cerebral blood flow. Here we provide new evidence for TRPV1 in promoting microvascular reperfusion following stroke. Hypothesis: Endothelial TRPV1 channels contribute to cerebral reperfusion following ischemic stroke. Methods: Experiments were performed in male WT and TRPV1 knockout mice of C57BL/6 background. Immunofluorescence was performed in brain sections with TRPV1 and Pecam-1 antibodies. Pressurized artery preparations were performed with isolated superior cerebellar arteries. Relative cerebral blood flow measurements were performed by laser Doppler and laser speckle flowmetry in mice before, during, and after MCAO (20 or 30 min). Reperfusion was monitored continuously for 2-3 hours and again at 24 hours. Results: TRPV1 expression was positively detected by immunofluorescence in the cerebral microvasculature, as assessed by Pecam-1 co-localization. TRPV1 KO mice were used as a negative control. Pressurized cerebral arteries demonstrated modest vasodilation to TRPV1 agonist (capsaicin) that was significantly potentiated with H 2 O 2 pre-treatment. The potentiated component of vasodilation was lost with removal of the endothelium, demonstrating the endothelial source of the response. Following brief MCA occlusion (20 or 30 min), WT mice demonstrated an initial return of cerebral perfusion followed by a transient drop in perfusion (~25% drop). This drop in perfusion started at 20-30 minutes into the reperfusion phase and lasted approximately one hour, at which point perfusion was restored to pre-stroke baseline value. In TRPV1 KO mice, the drop in perfusion was more profound (~65% drop) and persisted through 3 hours. By 24 hours, flow was restored to baseline in both groups. Conclusions: These data demonstrate a functional role for TRPV1 channels during reperfusion. We speculate that endothelial TRPV1 channels are functionally potentiated during injury and contribute to the vasodilatory capacity of the cerebral microvasculature following stroke.

scholarly journals Quantitative cerebral blood flow using xenon-enhanced CT after decompressive craniectomy in traumatic brain injury

2018 ◽  
Vol 129 (1) ◽  
pp. 241-246 ◽  
Author(s):  
Aditya Vedantam ◽  
Claudia S. Robertson ◽  
Shankar P. Gopinath
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Clinical Outcome ◽  
Decompressive Craniectomy ◽  
Decompressive Surgery ◽  
Hemodynamic Parameters ◽  
Enhanced Ct ◽  
The Mean

OBJECTIVEFew studies have reported on changes in quantitative cerebral blood flow (CBF) after decompressive craniectomy and the impact of these measures on clinical outcome. The aim of the present study was to evaluate global and regional CBF patterns in relation to cerebral hemodynamic parameters in patients after decompressive craniectomy for traumatic brain injury (TBI).METHODSThe authors studied clinical and imaging data of patients who underwent xenon-enhanced CT (XeCT) CBF studies after decompressive craniectomy for evacuation of a mass lesion and/or to relieve intractable intracranial hypertension. Cerebral hemodynamic parameters prior to decompressive craniectomy and at the time of the XeCT CBF study were recorded. Global and regional CBF after decompressive craniectomy was measured using XeCT. Regional cortical CBF was measured under the craniectomy defect as well as for each cerebral hemisphere. Associations between CBF, cerebral hemodynamics, and early clinical outcome were assessed.RESULTSTwenty-seven patients were included in this study. The majority of patients (88.9%) had an initial Glasgow Coma Scale score ≤ 8. The median time between injury and decompressive surgery was 9 hours. Primary decompressive surgery (within 24 hours) was performed in the majority of patients (n = 18, 66.7%). Six patients had died by the time of discharge. XeCT CBF studies were performed a median of 51 hours after decompressive surgery. The mean global CBF after decompressive craniectomy was 49.9 ± 21.3 ml/100 g/min. The mean cortical CBF under the craniectomy defect was 46.0 ± 21.7 ml/100 g/min. Patients who were dead at discharge had significantly lower postcraniectomy CBF under the craniectomy defect (30.1 ± 22.9 vs 50.6 ± 19.6 ml/100 g/min; p = 0.039). These patients also had lower global CBF (36.7 ± 23.4 vs 53.7 ± 19.7 ml/100 g/min; p = 0.09), as well as lower CBF for the ipsilateral (33.3 ± 27.2 vs 51.8 ± 19.7 ml/100 g/min; p = 0.07) and contralateral (36.7 ± 19.2 vs 55.2 ± 21.9 ml/100 g/min; p = 0.08) hemispheres, but these differences were not statistically significant. The patients who died also had significantly lower cerebral perfusion pressure (52 ± 17.4 vs 75.3 ± 10.9 mm Hg; p = 0.001).CONCLUSIONSIn the presence of global hypoperfusion, regional cerebral hypoperfusion under the craniectomy defect is associated with early mortality in patients with TBI. Further study is needed to determine the value of incorporating CBF studies into clinical decision making for severe traumatic brain injury.

The Influence of Inhaled Nitric Oxide on Cerebral Blood Flow and Metabolism in a Child with Traumatic Brain Injury

2001 ◽  
Vol 93 (2) ◽  
pp. 351-353 ◽  
Author(s):  
Monica S. Vavilala ◽  
Joan S. Roberts ◽  
Anne E. Moore ◽  
David W. Newell ◽  
Arthur M. Lam
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Inhaled Nitric Oxide

scholarly journals Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia

2015 ◽  
Vol 309 (7) ◽  
pp. F604-F616 ◽  
Author(s):  
R. Todd Alexander ◽  
Megan R. Beggs ◽  
Reza Zamani ◽  
Niels Marcussen ◽  
Sebastian Frische ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Transient Receptor Potential ◽  
Basolateral Membrane ◽  
Receptor Potential ◽  
Human Kidney ◽  
Muscle Layer ◽  
Transient Receptor Potential Vanilloid ◽  
Distal Nephron

Plasma membrane Ca2+-ATPases (PMCAs) participate in epithelial Ca2+ transport and intracellular Ca2+ signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca2+ channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca2+ flux and investigated the localization and regulation of Pmca4 in Ca2+-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In the kidney, Pmca4 showed broad localization to the distal nephron. In the mouse, expression was most abundant in segments coexpressing the epithelial ransient receptor potential vanilloid 5 Ca2+ channel. Significant, albeit lower, expression was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In the human kidney, a similar pattern of distribution was observed, with the highest PMCA4 expression in Na+-Cl− cotransporter-positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca2+ balance, pointing to a housekeeping function of the pump in Ca2+-transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca2+-transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca2+ transport.

scholarly journals Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension

2018 ◽  
Vol 315 (5) ◽  
pp. H1304-H1315 ◽  
Author(s):  
Janice M. Diaz-Otero ◽  
Ting-Chieh Yen ◽  
Courtney Fisher ◽  
Daniel Bota ◽  
William F. Jackson ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Angiotensin Ii ◽  
Mineralocorticoid Receptor ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Myogenic Tone ◽  
Transient Receptor Potential Vanilloid ◽  
Cerebrovascular Function ◽  
Transient Receptor

Hypertension and mineralocorticoid receptor activation cause cerebral parenchymal arteriole remodeling; this can limit cerebral perfusion and contribute to cognitive dysfunction. We used a mouse model of angiotensin II-induced hypertension to test the hypothesis that mineralocorticoid receptor activation impairs both transient receptor potential vanilloid (TRPV)4-mediated dilation of cerebral parenchymal arterioles and cognitive function. Mice (16−18 wk old, male, C57Bl/6) were treated with angiotensin II (800 ng·kg−1·min−1) with or without the mineralocorticoid receptor antagonist eplerenone (100 mg·kg−1·day−1) for 4 wk; sham mice served as controls. Data are presented as means ± SE; n = 5–14 mice/group. Eplerenone prevented the increased parenchymal arteriole myogenic tone and impaired carbachol-induced (10−9–10−5 mol/l) dilation observed during hypertension. The carbachol-induced dilation was endothelium-derived hyperpolarization mediated because it could not be blocked by N-nitro-l-arginine methyl ester (10−5 mol/l) and indomethacin (10−4 mol/l). We used GSK2193874 (10−7 mol/l) to confirm that in all groups this dilation was dependent on TRPV4 activation. Dilation in response to the TRPV4 agonist GSK1016790A (10−9–10−5 mol/l) was also reduced in hypertensive mice, and this defect was corrected by eplerenone. In hypertensive and eplerenone-treated animals, TRPV4 inhibition reduced myogenic tone, an effect that was not observed in arterioles from control animals. Eplerenone treatment also improved cognitive function and reduced microglia density in hypertensive mice. These data suggest that the mineralocorticoid receptor is a potential therapeutic target to improve cerebrovascular function and cognition during hypertension. NEW & NOTEWORTHY Vascular dementia is a growing public health issue that lacks effective treatments. Transient receptor potential vanilloid (TRPV)4 channels are important regulators of parenchymal arteriole dilation, and they modulate myogenic tone. The data presented here suggest that TRPV4 channel expression is regulated by the mineralocorticoid receptor (MR). MR blockade also improves cognitive function during hypertension. MR blockade might be a potential therapeutic approach to improve cerebrovascular function and cognition in patients with hypertension.

Cerebral Metabolism and Blood Flow Following Traumatic Brain Injury

2018 ◽  
Author(s):  
Ryan Martin ◽  
Lara Zimmermann ◽  
Marike Zwienenberg ◽  
Kee D Kim ◽  
Kiarash Shahlaie
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Cerebral Autoregulation ◽  
Cerebral Metabolism ◽  
Elevated Intracranial Pressure ◽  
Metabolic Demand ◽  
Cerebral Metabolic Rate

The management of traumatic brain injury focuses on the prevention of second insults, which most often occur because of a supply/demand mismatch of the cerebral metabolism. The healthy brain has mechanisms of autoregulation to match the cerebral blood flow to the cerebral metabolic demand. After trauma, these mechanisms are disrupted, leaving the patient susceptible to episodes of hypotension, hypoxemia, and elevated intracranial pressure. Understanding the normal and pathologic states of the cerebral blood flow is critical for understanding the treatment choices for a patient with traumatic brain injury. In this chapter, we discuss the underlying physiologic principles that govern our approach to the treatment of traumatic brain injury. This review contains 3 figures, 1 table and 12 references Key Words: cerebral autoregulation, cerebral blood flow, cerebral metabolic rate, intracranial pressure, ischemia, reactivity, vasoconstriction, vasodilation, viscosity

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