Cerebral tissue pO2 response to stimulation is preserved with age in awake mice

Moeini, Mohammad; Lu, Xuecong; Bélanger, Samuel; Picard, Frédéric; Boas, David A.; Kakkar, Ashok; Lesage, Frédéric

doi:10.1016/j.neulet.2019.02.007

Cited by 11 publications

(14 citation statements)

References 43 publications

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“…Two photon excitation substantially increases the spatial resolution and depth of measurement attainable using phosphorescence quenching, while retaining the method’s intrinsic accuracy, high temporal resolution, and minimal invasiveness. This technology advance is providing greater insight into oxygen delivery to tissue, including the role of cortical vasculature in brain metabolism and function ( Sakadžić et al, 2010 ; Devor et al, 2011 , 2014 ; Moeini et al, 2018 , 2019 ; Li et al, 2019 ; Şencan et al, 2020 ).…”

Section: On the Identity Of The Metabolic Sensor That Provides The Mementioning

confidence: 99%

“…As animals age, vascular function is progressively compromised due to effects of aging as modified by genetic, lifestyle, and disease related factors. Alterations with increasing age include vascular deformities ( Hassler, 1967 ), decreased vascular reactivity ( Mooradian and McCuskey, 1992 ), and perfusion ( Ruitenberg et al, 2005 ; Wolters et al, 2017 ; Zhang et al, 2010 ; Zheng et al, 2019 ), increase in oxygen extraction ( Ances et al, 2009 ; Zhang et al, 2010 ; Aanerud et al, 2012 ; Catchlove et al, 2018 ), decrease in tissue levels of oxygen ( Moeini et al, 2018 , 2019 ; Li et al, 2019 ), and increased hypoxia signaling through AMPK, HIF-1α, TGF-β, etc. ( Iadecola, 2010 , 2013 ; Wierenga et al, 2014 ).…”

Section: On the Primary Physiological Basis For Regulation Of Coronarmentioning

confidence: 99%

“…As noted above, chronic hypoxia has a role in increasing the incidence of vascular failure and augmenting the negative consequences. A partial list of diseases with overt vascular lesions includes Alzheimer’s, dementias, stroke, cerebral white matter disease, cerebral small vessel disease ( Fisher, 2010 ; Gorelick et al, 2011 ; Østergaard et al, 2015 ; Pinter et al, 2017 ; Bagi et al, 2018 ; Moeini et al, 2018 , 2019 ; Rajani et al, 2018 ; Nation et al, 2019 ; Sweeney et al, 2019 ). The vasculature of brain is continuously exposed to, and contributes to, humoral signaling such as inflammation.…”

Section: On the Primary Physiological Basis For Regulation Of Coronarmentioning

confidence: 99%

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Cerebrovascular Blood Flow Design and Regulation; Vulnerability in Aging Brain

Wilson

Matschinsky

2020

Front. Physiol.

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Nutrient delivery to the brain presents a unique challenge because the tissue functions as a computer system with in the order of 200,000 neurons/mm 3. Penetrating arterioles bud from surface arteries of the brain and penetrate downward through the cortex. Capillary networks spread from penetrating arterioles through the surrounding tissue. Each penetrating arteriole forms a vascular unit, with little sharing of flow among vascular units (collateral flow). Unlike cells in other tissues, neurons have to be operationally isolated, interacting with other neurons through specific electrical connections. Neuronal activation typically involves only a few of the cells within a vascular unit, but the local increase in nutrient consumption is substantial. The metabolic response to activation is transmitted to the feeding arteriole through the endothelium of neighboring capillaries and alters calcium permeability of smooth muscle in the wall resulting in modulation of flow through the entire vascular unit. Many age and trauma related brain pathologies can be traced to vascular malfunction. This includes: 1. Physical damage such as in traumatic injury with imposed shear stress as soft tissue moves relative to the skull. Lack of collateral flow among vascular units results in death of the cells in that vascular unit and loss of brain tissue. 2. Age dependent changes lead to progressive increase in vascular resistance and decrease in tissue levels of oxygen and glucose. Chronic hypoxia/hypoglycemia compromises tissue energy metabolism and related regulatory processes. This alters stem cell proliferation and differentiation, undermines vascular integrity, and suppresses critical repair mechanisms such as oligodendrocyte generation and maturation. Reduced structural integrity results in local regions of acute hypoxia and microbleeds, while failure of oligodendrocytes to fully mature leads to poor axonal myelination and defective neuronal function. Understanding and treating age related pathologies, particularly in brain, requires better knowledge of why and how vasculature changes with age. That knowledge will, hopefully, make possible drugs/methods for protecting vascular function, substantially alleviating the negative health and cognitive deficits associated with growing old.

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Section: On the Identity Of The Metabolic Sensor That Provides The Mementioning

confidence: 99%

Section: On the Primary Physiological Basis For Regulation Of Coronarmentioning

confidence: 99%

Section: On the Primary Physiological Basis For Regulation Of Coronarmentioning

confidence: 99%

See 1 more Smart Citation

Cerebrovascular Blood Flow Design and Regulation; Vulnerability in Aging Brain

Wilson

Matschinsky

2020

Front. Physiol.

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“…Following line scanning, 3D angiograms were obtained over four overlapping 600 × 600 µm (400 × 400 pixels) regions at depths of 100-550 µm with 5-µm steps at a frame rate of 0.5 Hz. During all measurements, animals were awake, with the head fixed by a titanium bar and limbs free to move on the rotating wheel (Moeini et al, 2018(Moeini et al, , 2019.…”

Section: Two-photon Imagingmentioning

confidence: 99%

A Pilot Study Investigating Changes in Capillary Hemodynamics and Its Modulation by Exercise in the APP-PS1 Alzheimer Mouse Model

Moeini

et al. 2019

Front. Neurosci.

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Dysfunction in neurovascular coupling that results in a mismatch between cerebral blood flow and neuronal activity has been suggested to play a key role in the pathogenesis of Alzheimer's disease (AD). Meanwhile, physical exercise is a powerful approach for maintaining cognitive health and could play a preventive role against the progression of AD. Given the fundamental role of capillaries in oxygen transport to tissue, our pilot study aimed to characterize changes in capillary hemodynamics with AD and AD supplemented by exercise. Exploiting two-photon microscopy, intrinsic signal optical imaging, and magnetic resonance imaging, we found hemodynamic alterations and lower vascular density with AD that were reversed by exercise. We further observed that capillary properties were branch order-dependent and that stimulation-evoked changes were attenuated with AD but increased by exercise. Our study provides novel indications into cerebral microcirculatory disturbances with AD and the modulating role of voluntary exercise on these alterations.

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“…Exercise induces changes in the cerebral metabolic rate of oxygen (CMRO 2 ) [1][2][3][4] and increases demand on the cardiovascular and pulmonary systems, with subsequent effects on cerebral vascular oxygenation and cognitive function [5][6][7] . While cerebral tissue pO 2 at rest and during neural stimulation has been the subject of several studies in awake and anesthetized subjects [8][9][10][11][12][13] , the response of cerebral tissue pO 2 to acute exercise has not been described.…”

mentioning

confidence: 99%

Cerebral tissue pO2 response to treadmill exercise in awake mice

Moeini

Cloutier-Tremblay

et al. 2020

Sci Rep

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We exploited two-photon microscopy and Doppler optical coherence tomography to examine the cerebral blood flow and tissue pO 2 response to forced treadmill exercise in awake mice. to our knowledge, this is the first study performing both direct measure of brain tissue pO 2 during acute forced exercise and underlying microvascular response at capillary and non-capillary levels. We observed that cerebral perfusion and oxygenation are enhanced during running at 5 m/min compared to rest. At faster running speeds (10 and 15 m/min), decreasing trends in arteriolar and capillary flow speed were observed, which could be due to cerebral autoregulation and constriction of arterioles in response to blood pressure increase. However, tissue pO 2 was maintained, likely due to an increase in RBC linear density. Higher cerebral oxygenation at exercise levels 5-15 m/min suggests beneficial effects of exercise in situations where oxygen delivery to the brain is compromised, such as in aging, atherosclerosis and Alzheimer Disease.

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Cerebral tissue pO2 response to stimulation is preserved with age in awake mice

Cited by 11 publications

References 43 publications

Cerebrovascular Blood Flow Design and Regulation; Vulnerability in Aging Brain

Cerebrovascular Blood Flow Design and Regulation; Vulnerability in Aging Brain

A Pilot Study Investigating Changes in Capillary Hemodynamics and Its Modulation by Exercise in the APP-PS1 Alzheimer Mouse Model

Cerebral tissue pO2 response to treadmill exercise in awake mice

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