Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool

The brain has a high energy demand but little to no energy stores. Therefore, proper brain function relies on the delivery of glucose and oxygen by the cerebral vasculature. The regulation of cerebral blood flow (CBF) occurs at the level of the cerebral capillaries and is driven by a fast and effici...

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Autores principales:	Fatma Burcu Seker, Ziyu Fan, Benno Gesierich, Malo Gaubert, Rebecca Isabella Sienel, Nikolaus Plesnila
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	neurovascular coupling hypercapnia laser speckle contrast imaging two-photon microscopy aging investigator-independent analysis Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/49246a5385ee469f8b59d06386176ffa
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spelling	oai:doaj.org-article:49246a5385ee469f8b59d06386176ffa2021-11-11T04:59:36ZNeurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool1664-229510.3389/fneur.2021.745770https://doaj.org/article/49246a5385ee469f8b59d06386176ffa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.745770/fullhttps://doaj.org/toc/1664-2295The brain has a high energy demand but little to no energy stores. Therefore, proper brain function relies on the delivery of glucose and oxygen by the cerebral vasculature. The regulation of cerebral blood flow (CBF) occurs at the level of the cerebral capillaries and is driven by a fast and efficient crosstalk between neurons and vessels, a process termed neurovascular coupling (NVC). Experimentally NVC is mainly triggered by sensory stimulation and assessed by measuring either CBF by laser Doppler fluxmetry, laser speckle contrast imaging (LSCI), intrinsic optical imaging, BOLD fMRI, near infrared spectroscopy (NIRS) or functional ultrasound imaging (fUS). Since these techniques have relatively low spatial resolution, diameters of cerebral vessels are mainly assessed by 2-photon microscopy (2-PM). Results of studies on NVC rely on stable animal physiology, high-quality data acquisition, and unbiased data analysis, criteria, which are not easy to achieve. In the current study, we assessed NVC using two different imaging modalities, i.e., LSCI and 2-PM, and analyzed our data using an investigator-independent Matlab-based analysis tool, after manually defining the area of analysis in LSCI and vessels to measure in 2-PM. By investigating NVC in 6–8 weeks, 1-, and 2-year-old mice, we found that NVC was maximal in 1-year old mice and was significantly reduced in aged mice. These findings suggest that NVC is differently affected during the aging process. Most interestingly, specifically pial arterioles, seem to be distinctly affected by the aging. The main finding of our study is that the automated analysis tool works very efficiently in terms of time and accuracy. In fact, the tool reduces the analysis time of one animal from approximately 23 h to about 2 s while basically making no mistakes. In summary, we developed an experimental workflow, which allows us to reliably measure NVC with high spatial and temporal resolution in young and aged mice and to analyze these data in an investigator-independent manner.Fatma Burcu SekerZiyu FanBenno GesierichMalo GaubertRebecca Isabella SienelNikolaus PlesnilaNikolaus PlesnilaFrontiers Media S.A.articleneurovascular couplinghypercapnialaser speckle contrast imagingtwo-photon microscopyaginginvestigator-independent analysisNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neurovascular coupling hypercapnia laser speckle contrast imaging two-photon microscopy aging investigator-independent analysis Neurology. Diseases of the nervous system RC346-429
spellingShingle	neurovascular coupling hypercapnia laser speckle contrast imaging two-photon microscopy aging investigator-independent analysis Neurology. Diseases of the nervous system RC346-429 Fatma Burcu Seker Ziyu Fan Benno Gesierich Malo Gaubert Rebecca Isabella Sienel Nikolaus Plesnila Nikolaus Plesnila Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool
description	The brain has a high energy demand but little to no energy stores. Therefore, proper brain function relies on the delivery of glucose and oxygen by the cerebral vasculature. The regulation of cerebral blood flow (CBF) occurs at the level of the cerebral capillaries and is driven by a fast and efficient crosstalk between neurons and vessels, a process termed neurovascular coupling (NVC). Experimentally NVC is mainly triggered by sensory stimulation and assessed by measuring either CBF by laser Doppler fluxmetry, laser speckle contrast imaging (LSCI), intrinsic optical imaging, BOLD fMRI, near infrared spectroscopy (NIRS) or functional ultrasound imaging (fUS). Since these techniques have relatively low spatial resolution, diameters of cerebral vessels are mainly assessed by 2-photon microscopy (2-PM). Results of studies on NVC rely on stable animal physiology, high-quality data acquisition, and unbiased data analysis, criteria, which are not easy to achieve. In the current study, we assessed NVC using two different imaging modalities, i.e., LSCI and 2-PM, and analyzed our data using an investigator-independent Matlab-based analysis tool, after manually defining the area of analysis in LSCI and vessels to measure in 2-PM. By investigating NVC in 6–8 weeks, 1-, and 2-year-old mice, we found that NVC was maximal in 1-year old mice and was significantly reduced in aged mice. These findings suggest that NVC is differently affected during the aging process. Most interestingly, specifically pial arterioles, seem to be distinctly affected by the aging. The main finding of our study is that the automated analysis tool works very efficiently in terms of time and accuracy. In fact, the tool reduces the analysis time of one animal from approximately 23 h to about 2 s while basically making no mistakes. In summary, we developed an experimental workflow, which allows us to reliably measure NVC with high spatial and temporal resolution in young and aged mice and to analyze these data in an investigator-independent manner.
format	article
author	Fatma Burcu Seker Ziyu Fan Benno Gesierich Malo Gaubert Rebecca Isabella Sienel Nikolaus Plesnila Nikolaus Plesnila
author_facet	Fatma Burcu Seker Ziyu Fan Benno Gesierich Malo Gaubert Rebecca Isabella Sienel Nikolaus Plesnila Nikolaus Plesnila
author_sort	Fatma Burcu Seker
title	Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool
title_short	Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool
title_full	Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool
title_fullStr	Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool
title_full_unstemmed	Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool
title_sort	neurovascular reactivity in the aging mouse brain assessed by laser speckle contrast imaging and 2-photon microscopy: quantification by an investigator-independent analysis tool
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/49246a5385ee469f8b59d06386176ffa
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Neurovascular Reactivity in the Aging Mouse Brain Assessed by Laser Speckle Contrast Imaging and 2-Photon Microscopy: Quantification by an Investigator-Independent Analysis Tool

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