Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise

2012 ◽  
Vol 112 (1) ◽  
pp. 197-203 ◽  
Author(s):  
Takeshi Nishijima ◽  
Masahiro Okamoto ◽  
Takashi Matsui ◽  
Ichiro Kita ◽  
Hideaki Soya
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nmda Receptor ◽  
Neuronal Activity ◽  
Treadmill Running ◽  
Functional Hyperemia ◽  
Neuronal Activation ◽  
Metabotropic Glutamate ◽  
Group I ◽  
No Signaling

Current studies have demonstrated that exercise increases regional cerebral blood flow (rCBF), an index of neuronal activity. However, neuronal regulation of the increased rCBF in the brain parenchyma is poorly understood. We developed a running model with rats for monitoring hippocampal cerebral blood flow (Hip-CBF) and found that mild treadmill running increases Hip-CBF in a tetrodotoxin-dependent manner, suggesting that functional hyperemia, an increase in rCBF in response to neuronal activation, occurs in the running rat's hippocampus (Nishijima T and Soya H. Neurosci Res 54: 186–191, 2006). To further support our hypothesis, it was important to discover the neurogenic pathways behind the increase in Hip-CBF that occurred during running. Here, we examine the possible role of N-methyl-d-aspartate (NMDA) receptor/nitric oxide (NO) signaling and group I metabotropic glutamate receptors in mediating the Hip-CBF increase. Hip-CBF during running was measured by laser-Doppler flowmetry. Intrahippocampal drug administration was performed by microdialysis. Mild treadmill running (10 m/min) increased Hip-CBF, which was remarkably attenuated by either NMDA receptor antagonists (1 mM MK-801) or NO synthase inhibitors (2 mM NG-nitro-l-arginine methyl ester). However, group I metabotropic glutamate receptor antagonists {1 mM 7-(hydroxyimino)cyclopropa[ b]chromen-1a-carboxylate ethyl ester + 1 mM 2-methyl-6-(phenylethynyl)pyridine hydrochloride} augmented the running-induced Hip-CBF increase. We also found that rCBF in the olfactory bulb was unchanged with running. These results strongly suggest that Hip-CBF during mild exercise is regulated locally under hippocampal neuronal activity, mediated mainly through NMDA receptor/NO signaling. Collectively, these results, together with our previous findings, support our hypothesis that mild exercise elicits neuronal activation, which then triggers functional hyperemia in the rat hippocampus.

scholarly journals Diverse Functions of Pericytes in Cerebral Blood Flow Regulation and Ischemia

2015 ◽  
Vol 35 (6) ◽  
pp. 883-887 ◽  
Author(s):  
Francisco Fernandez-Klett ◽  
Josef Priller
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Neuronal Activity ◽  
Flow Regulation ◽  
Functional Hyperemia ◽  
Mural Cells ◽  
Ischemic Tissue ◽  
The Brain

Pericytes are mural cells with contractile properties. Here, we provide evidence that microvascular pericytes modulate cerebral blood flow in response to neuronal activity (‘functional hyperemia’). Besides their role in neurovascular coupling, pericytes are responsive to brain damage. Cerebral ischemia is associated with constrictions and death of capillary pericytes, followed by fibrotic reorganization of the ischemic tissue. The data suggest that precapillary arterioles and capillaries are major sites of hemodynamic regulation in the brain.

scholarly journals Nitric Oxide Pathways in Neurovascular Coupling Under Normal and Stress Conditions in the Brain: Strategies to Rescue Aberrant Coupling and Improve Cerebral Blood Flow

2021 ◽  
Vol 12 ◽  
Author(s):  
Cátia F. Lourenço ◽  
João Laranjinha
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nmda Receptor ◽  
Neuronal Activity ◽  
Energy Requirements ◽  
Neuronal Dysfunction ◽  
No Bioavailability ◽  
The Brain

The brain has impressive energy requirements and paradoxically, very limited energy reserves, implying its huge dependency on continuous blood supply. Aditionally, cerebral blood flow must be dynamically regulated to the areas of increased neuronal activity and thus, of increased metabolic demands. The coupling between neuronal activity and cerebral blood flow (CBF) is supported by a mechanism called neurovascular coupling (NVC). Among the several vasoactive molecules released by glutamatergic activation, nitric oxide (•NO) is recognized to be a key player in the process and essential for the development of the neurovascular response. Classically, •NO is produced in neurons upon the activation of the glutamatergic N-methyl-D-aspartate (NMDA) receptor by the neuronal isoform of nitric oxide synthase and promotes vasodilation by activating soluble guanylate cyclase in the smooth muscle cells of the adjacent arterioles. This pathway is part of a more complex network in which other molecular and cellular intervenients, as well as other sources of •NO, are involved. The elucidation of these interacting mechanisms is fundamental in understanding how the brain manages its energy requirements and how the failure of this process translates into neuronal dysfunction. Here, we aimed to provide an integrated and updated perspective of the role of •NO in the NVC, incorporating the most recent evidence that reinforces its central role in the process from both viewpoints, as a physiological mediator and a pathological stressor. First, we described the glutamate-NMDA receptor-nNOS axis as a central pathway in NVC, then we reviewed the link between the derailment of the NVC and neuronal dysfunction associated with neurodegeneration (with a focus on Alzheimer’s disease). We further discussed the role of oxidative stress in the NVC dysfunction, specifically by decreasing the •NO bioavailability and diverting its bioactivity toward cytotoxicity. Finally, we highlighted some strategies targeting the rescue or maintenance of •NO bioavailability that could be explored to mitigate the NVC dysfunction associated with neurodegenerative conditions. In line with this, the potential modulatory effects of dietary nitrate and polyphenols on •NO-dependent NVC, in association with physical exercise, may be used as effective non-pharmacological strategies to promote the •NO bioavailability and to manage NVC dysfunction in neuropathological conditions.

Role of endothelium-pericyte signaling in capillary blood flow response to neuronal activity

2021 ◽  
pp. 0271678X2110079
Author(s):  
Wenri Zhang ◽  
Catherine M Davis ◽  
Douglas M Zeppenfeld ◽  
Kirsti Golgotiu ◽  
Marie X Wang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Neuronal Activity ◽  
Functional Hyperemia ◽  
Neuronal Activation ◽  
Two Photon Microscopy ◽  
Tightly Coupled ◽  
Whisker Stimulation ◽  
Optical Microangiography ◽  
Hyperemic Response

Local blood flow in the brain is tightly coupled to metabolic demands, a phenomenon termed functional hyperemia. Both capillaries and arterioles contribute to the hyperemic response to neuronal activity via different mechanisms and timescales. The nature and specific signaling involved in the hyperemic response of capillaries versus arterioles, and their temporal relationship are not fully defined. We determined the time-dependent changes in capillary flux and diameter versus arteriolar velocity and flow following whisker stimulation using optical microangiography (OMAG) and two-photon microscopy. We further characterized depth-resolved responses of individual capillaries versus capillary networks. We hypothesized that capillaries respond first to neuronal activation, and that they exhibit a coordinated response mediated via endothelial-derived epoxyeicosatrienoates (EETs) acting on pericytes. To visualize peri-capillary pericytes, we used Tie2-GFP/NG2-DsRed mice, and to determine the role of endothelial-derived EETs, we compared cerebrovascular responses to whisker stimulation between wild-type mice and mice with lower endothelial EETs (Tie2-hsEH). We found that capillaries respond immediately to neuronal activation in an orchestrated network-level manner, a response attenuated in Tie2-hsEH and inhibited by blocking EETs action on pericytes. These results demonstrate that capillaries are first responders during functional hyperemia, and that they exhibit a network-level response mediated via endothelial-derived EETs’ action on peri-capillary pericytes.

Abstract T P178: Cerebral Blood Flow and Metabolism Associated with Cerebral Microbleeds in Patients with Non-cardioembolic Stroke Without Major Cerebral Arterial Stenosis

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Tetsuya Hashimoto ◽  
Chiaki Yokota ◽  
Ryo Shimomura ◽  
Kazuhiro Koshino ◽  
Toshiyuki Uehara ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Cerebral Blood Volume ◽  
Cerebral Microbleeds ◽  
Cardioembolic Stroke ◽  
Arterial Stenosis ◽  
Oxygen Extraction Fraction ◽  
Group I ◽  
Group Ii

Background and Purpose: Cerebral microbleeds (CMBs) are associated with not only higher age but also extensive white matter lesions (WMLs), indicating that CMBs could be a reflection of microangiopathy. CMBs have not yet been examined in association with cerebral blood flow (CBF) and metabolism. The purpose of this study was to clarify the relationships of CMBs with WMLs volume, and CBF and metabolism in patients with ischemic stroke. Methods: We enrolled 19 patients who had past history of non-cardioembolic stroke without severe stenosis (>50%) in major cerebral arteries (69±7 years, 9 women). We measured WMLs volume and counted the number of CMBs on a 1.5-T magnetic resonance imaging (MRI) scanner. CBF, cerebral blood volume, oxygen extraction fraction and cerebral metabolic rate of oxygen were measured with 15 O-labeled gas positron emission tomography (PET). We set 36 regions of interest (ROIs) in the cortex-subcortex regions, basal ganglia and centra semiovale in each patient on MRI. MRI was superimposed on PET images and 4 parameters of each ROI were calculated. Results: CMBs existed in 14 out of 19 patients (median 5; range 0-39). Patients were divided into 2 groups according to the number of CMBs; less than 5 as the group I (n=9) and 5 or more as the group II (n=10). WMLs volume of the group II was larger than that of the group I (median 38.4 with range of 25.1-91.5 vs. 10.0 with 4.2-73.4 ml, p=0.020). In the centra semiovale, CBF of the group II was significantly lower than that of the group I (12.5±2.5 vs. 15.7±3.5 ml/100g/min, p=0.031). In the other regions, there were no significant differences in all 4 parameters of PET between the 2 groups. Conclusions: We showed that the increases in the number of CMBs could indicate cerebral ischemia in the deep white matter of patients with non-cardioembolic stroke without major cerebral arterial stenosis.

scholarly journals Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein Autofluorescence Corrected for Cerebral Blood Flow

2018 ◽  
Vol 11 ◽  
Author(s):  
Manami Takahashi ◽  
Takuya Urushihata ◽  
Hiroyuki Takuwa ◽  
Kazumi Sakata ◽  
Yuhei Takado ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Neuronal Activity
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