Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition

Lake, Evelyn M. R.; Mester, James R.; Thomason, Lynsie A.M.; Adams, C.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Janik, Rafal; Carlen, Peter L.; McLaurin, JoAnne; Stanisz, Greg J.; Stefanović, Bojana

doi:10.1002/jmri.25541

Cited by 10 publications

(5 citation statements)

References 39 publications

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“…However, to date, use of propofol in disease models such as ischemic stroke is limited to a few studies observing changes in global CBF in response to hypercapnia. 53,83 While for practical reasons, anesthetizing animals for MRI studies has been the norm, protocols have been developed for scanning awake animals. 9,71 The benefit of this is clear, rendering animals unconscious affects brain and vascular activity, so functional responses in an anesthetized animal are different from those in an awake animal.…”

Section: Methodological Considerations Relevant To Preclinical Stroke Imagingmentioning

confidence: 99%

Imaging Functional Recovery Following Ischemic Stroke: Clinical and Preclinical fMRI Studies

Crofts

Kelly

Gibson

2019

Journal of Neuroimaging

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Disability and effectiveness of physical therapy are highly variable following ischemic stroke due to different brain regions being affected. Functional magnetic resonance imaging (fMRI) studies of patients in the months and years following stroke have given some insight into how the brain recovers lost functions. Initially, new pathways are recruited to compensate for the lost region, showing as a brighter blood oxygen-level-dependent (BOLD) signal over a larger area during a task than in healthy controls. Subsequently, activity is reduced to baseline levels as pathways become more efficient, mimicking the process of learning typically seen during development. Preclinical models of ischemic stroke aim to enhance understanding of the biology underlying recovery following stroke. However, the pattern of recruitment and focusing seen in humans has not been observed in preclinical fMRI studies that are highly variable methodologically. Resting-state fMRI studies show more consistency; however, there are still confounding factors to address. Anesthesia and method of stroke induction are the two main sources of variability in preclinical studies; improvements here can reduce variability and increase the intensity and reproducibility of the BOLD response detected by fMRI. Differences in task or stimulus and differences in analysis method also present a source of variability. This review compares clinical and preclinical fMRI studies of recovery following stroke and focuses on how refinement of preclinical models and MRI methods may obtain more representative fMRI data in relation to human studies.

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Section: Methodological Considerations Relevant To Preclinical Stroke Imagingmentioning

confidence: 99%

Imaging Functional Recovery Following Ischemic Stroke: Clinical and Preclinical fMRI Studies

Crofts

Kelly

Gibson

2019

Journal of Neuroimaging

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“…The region analyzed spanned from ~0.2 mm below cortical surface to ~1.2 mm below cortical surface, corresponding to cortical layers II through VI (given 1.4 mm cortical thickness in this coronal slab). Image analysis was performed using ImageJ following previous work 25 . Briefly, images underwent edge detection, background subtraction, and binarization via ImageJ's MakeBinary algorithm.…”

Section: Methodsmentioning

confidence: 99%

Neurogliovascular dysfunction in a model of repeated traumatic brain injury

et al. 2018

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Traumatic brain injury (TBI) research has focused on moderate to severe injuries as their outcomes are significantly worse than those of a mild TBI (mTBI). However, recent epidemiological evidence has indicated that a series of even mild TBIs greatly increases the risk of neurodegenerative and psychiatric disorders. Neuropathological studies of repeated TBI have identified changes in neuronal ionic concentrations, axonal injury, and cytoskeletal damage as important determinants of later life neurological and mood compromise; yet, there is a paucity of data on the contribution of neurogliovascular dysfunction to the progression of repeated TBI and alterations of brain function in the intervening period.Methods: Here, we established a mouse model of repeated TBI induced via three electromagnetically actuated impacts delivered to the intact skull at three-day intervals and determined the long-term deficits in neurogliovascular functioning in Thy1-ChR2 mice. Two weeks post the third impact, cerebral blood flow and cerebrovascular reactivity were measured with arterial spin labelling magnetic resonance imaging. Neuronal function was investigated through bilateral intracranial electrophysiological responses to optogenetic photostimulation. Vascular density of the site of impacts was measured with in vivo two photon fluorescence microscopy. Pathological analysis of neuronal survival and astrogliosis was performed via NeuN and GFAP immunofluorescence.Results: Cerebral blood flow and cerebrovascular reactivity were decreased by 50±16% and 70±20%, respectively, in the TBI cohort relative to sham-treated animals. Concomitantly, electrophysiological recordings revealed a 97±1% attenuation in peri-contusional neuronal reactivity relative to sham. Peri-contusional vascular volume was increased by 33±2% relative to sham-treated mice. Pathological analysis of the peri-contusional cortex demonstrated astrogliosis, but no changes in neuronal survival.Conclusion: This work provides the first in-situ characterization of the long-term deficits of the neurogliovascular unit following repeated TBI. The findings will help guide the development of diagnostic markers as well as therapeutics targeting neurogliovascular dysfunction.

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“…Activated perivascular microglia may also be able to control repair of the damaged BBB [ 200 , 201 ], as well as to induce or support angiogenesis, which is important in CNS tumours [ 202 , 203 ] and vascular pathologies of the retina [ 204 – 207 ]. First experimental therapeutic approaches have been suggested [ 208 ], but more research is required. Substantial research of this topic has used live animal imaging [ 209 , 210 ], often the retina model, as the blood vessels of the eye are easily monitored.…”

Section: Introductionmentioning

confidence: 99%

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

et al. 2017

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Microglia cells are the unique residential macrophages of the central nervous system (CNS). They have a special origin, as they derive from the embryonic yolk sac and enter the developing CNS at a very early stage. They play an important role during CNS development and adult homeostasis. They have a major contribution to adult neurogenesis and neuroinflammation. Thus, they participate in the pathogenesis of neurodegenerative diseases and contribute to aging. They play an important role in sustaining and breaking the blood-brain barrier. As innate immune cells, they contribute substantially to the immune response against infectious agents affecting the CNS. They play also a major role in the growth of tumours of the CNS. Microglia are consequently the key cell population linking the nervous and the immune system. This review covers all different aspects of microglia biology and pathology in a comprehensive way.

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Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition

Abstract: 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;46:505-517.

Cited by 10 publications

References 39 publications

Imaging Functional Recovery Following Ischemic Stroke: Clinical and Preclinical fMRI Studies

Imaging Functional Recovery Following Ischemic Stroke: Clinical and Preclinical fMRI Studies

Neurogliovascular dysfunction in a model of repeated traumatic brain injury

Microglia at center stage: a comprehensive review about the versatile and unique residential macrophages of the central nervous system

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