Cholinergic control of the cerebral vasculature in humans

The diagnosis, prognosis, and treatment of mild traumatic brain injuries (mTBIs), such as concussions, are significant unmet medical issues. The kinetic forces that occur in mTBI adversely affect the cerebral vasculature, making cerebrovascular injury (CVI) a pathophysiological hallmark of mTBI. Given the importance of a healthy cerebrovascular system in overall brain function, CVI is likely to contribute to neurological dysfunction after mTBI. As such, CVI and related pathomechanisms may provide objective biomarkers and therapeutic targets to improve the clinical management and outcomes of mTBI. Despite this potential, until recently, few studies have focused on the cerebral vasculature in this context. This article will begin by providing a brief overview of the cerebrovascular system followed by a review of the literature regarding how mTBI can affect the integrity and function of the cerebrovascular system, and how this may ultimately contribute to neurological dysfunction and neurodegenerative conditions. We then discuss promising avenues of research related to mTBI biomarkers and interventions that target CVI, and conclude that a clinical approach that takes CVI into account could result in substantial improvements in the care and outcomes of patients with mTBI.

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Automatic segmentation, feature extraction and comparison of healthy and stroke cerebral vasculature

NeuroImage Clinical ◽

10.1016/j.nicl.2021.102573 ◽

2021 ◽

Vol 30 ◽

pp. 102573

Author(s):

Aditi Deshpande ◽

Nima Jamilpour ◽

Bin Jiang ◽

Patrik Michel ◽

Ashraf Eskandari ◽

...

Keyword(s):

Feature Extraction ◽

Automatic Segmentation ◽

Cerebral Vasculature

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Teaching NeuroImages: Abnormal cervical and cerebral vasculature in 22q11 deletion syndrome

Neurology ◽

10.1212/wnl.0000000000004065 ◽

2017 ◽

Vol 89 (1) ◽

pp. e6-e6

Author(s):

Divakar S. Mithal ◽

Jonathan E. Kurz

Keyword(s):

Deletion Syndrome ◽

22Q11 Deletion ◽

Cerebral Vasculature ◽

22Q11 Deletion Syndrome

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Nogo-B receptor deficiency causes cerebral vasculature defects during embryonic development in mice

Developmental Biology ◽

10.1016/j.ydbio.2015.12.023 ◽

2016 ◽

Vol 410 (2) ◽

pp. 190-201 ◽

Cited By ~ 12

Author(s):

Ujala Rana ◽

Zhong Liu ◽

Suresh N. Kumar ◽

Baofeng Zhao ◽

Wenquan Hu ◽

...

Keyword(s):

Embryonic Development ◽

Cerebral Vasculature

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Effects of Ionizing Radiation on Cerebral Vasculature

World Neurosurgery ◽

10.1016/j.wneu.2014.01.006 ◽

2014 ◽

Vol 81 (3-4) ◽

pp. 490-491 ◽

Cited By ~ 5

Author(s):

Joshua Lucas ◽

William J. Mack

Keyword(s):

Ionizing Radiation ◽

Cerebral Vasculature

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Improved Histologic Analysis of Component Distribution and Wall Behavior in Cyanoacrylate-Embolized Vessels

10.1115/imece2001/bed-23131 ◽

2001 ◽

Author(s):

William J. Calvo ◽

Baruch B. Lieber ◽

Ajay K. Wakhloo ◽

L. Nelson Hopkins

Keyword(s):

Acetic Acid ◽

Contrast Agent ◽

Treatment Modality ◽

Arteriovenous Malformations ◽

Glacial Acetic Acid ◽

Cerebral Vasculature ◽

Polymerization Time ◽

Component Distribution ◽

Embolic Agents ◽

The Us

Abstract Use of embolic agents is currently an accepted treatment modality among neurointerventional clinicians in order to completely occlude abnormal shunts in the cerebral vasculature known as arteriovenous malformations or AVMs. The first cyanoacrylate polymer recently approved by the US Food and Drug Administration for use in humans is n-butyl 2-cyanoacrylate (NBCA). In order to control the polymerization time of NBCA, as well as to opacify the mixture for angiographic visualization, an iodized poppyseed oil-based contrast agent (Lipiodol) is added to the NBCA. Glacial acetic acid is also used to delay polymerization further by decreasing the pH of the mixture.

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Effects of Radiation on Cerebral Vasculature: A Review

Neurosurgery ◽

10.1093/neurosurgery/46.1.138 ◽

2000 ◽

Vol 46 (1) ◽

pp. 138-151 ◽

Cited By ~ 66

Author(s):

Michael M. O'Connor ◽

Marc R. Mayberg

Keyword(s):

Cerebral Vasculature ◽

Effects Of Radiation

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Targeted Regulation Of Cgrp Gene Expression

The Scientific World JOURNAL ◽

10.1100/tsw.2001.438 ◽

2001 ◽

Vol 1 ◽

pp. 5-5 ◽

Cited By ~ 1

Author(s):

A. F. Russo ◽

P. L. Durham

Keyword(s):

Map Kinase ◽

Therapeutic Strategy ◽

Adenoviral Vectors ◽

Calcium Signal ◽

Trigeminal Ganglia ◽

Cerebral Vasculature ◽

Trigeminal Neuron ◽

Calcitonin Gene ◽

Gene Enhancer ◽

A Cell

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent regulator of cerebral vascular tone and contributes to neurogenic inflammation. Clinical studies have shown that CGRP levels are elevated during the painful phase of migraine headache, then restored to baseline by antimigraine 5-HT1 drugs. Conversely, CGRP is depleted in perivascular nerve terminals from patients who have suffered vasospasm following subarachnoid hemorrhage. We have investigated the mechanisms controlling CGRP expression in the trigeminal ganglia neurons, which provide virtually all of the CGRP innervation to the cerebral vasculature. We found that nerve depolarization, inflammatory compounds, and nitric oxide can increase CGRP synthesis and secretion. Using both adenoviral vectors and transfection approaches, we have shown that the increased synthesis is due to activation of a cell-specific MAP kinase-responsive enhancer upstream of the CGRP gene. Interestingly, the 5-HT1 migraine drugs are able to block this up-regulation by a mechanism that involves a very prolonged elevation of calcium. We have shown that the duration of the calcium signal is a key determinant for whether a MAP kinase responsive gene will be stimulated or repressed by calcium-activated pathways. This observation supports the importance of a finely tuned balance of calcium in the trigeminal neuron, which is intriguing in light of genetic evidence for calcium channel mutations in a rare form of inherited migraine. These studies suggest that modulation of MAP kinase control of the cell-specific CGRP gene enhancer may be a useful therapeutic strategy for neurovascular disorders.

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Multiple forms of estrogen receptor-α in cerebral blood vessels: regulation by estrogen

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00165.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. E184-E192 ◽

Cited By ~ 74

Author(s):

Chris Stirone ◽

Sue P. Duckles ◽

Diana N. Krause

Keyword(s):

Estrogen Receptor ◽

Blood Vessels ◽

Estrogen Receptor Α ◽

26S Proteasome ◽

Target Tissue ◽

Female Rat ◽

Cerebral Vasculature ◽

Cerebral Blood Vessels ◽

Multiple Forms

The cerebral vasculature is an important target tissue for estrogen, as evidenced by significant effects of estrogen on vascular reactivity and protein levels of endothelial nitric oxide synthase and prostacyclin synthase. However, the presence, localization, and regulation of estrogen receptors in the cerebral vasculature have not been investigated. In this study, we identified the presence of estrogen receptor-α (ER-α) in female rat cerebral blood vessels and localized this receptor to both smooth muscle and endothelial cells by use of immunohistochemistry and confocal microscopy. With immunoblot analysis, multiple forms of ER-α were detected at 110, 93, 82, 50, and 45 kDa in addition to a relatively weak band corresponding to the 66-kDa putative unmodified receptor. The 82-kDa band was identified as Ser118-phosphorylated ER-α, whereas the 50-kDa band lacks the normal NH2 terminus, suggestive of an ER-α splice variant. Lower molecular mass bands persisted after in vivo inhibition of 26S proteasome activity with lactacystin, whereas the 110- and 93-kDa bands increased. All forms of ER-α in cerebral vessels were decreased after ovariectomy but significantly increased after chronic estrogen exposure in vivo.

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Intact female stroke-prone hypertensive rats lack responsiveness to mineralocorticoid receptor antagonists

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00145.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. R1754-R1763 ◽

Cited By ~ 19

Author(s):

Christiné S. Rigsby ◽

Ashley E. Burch ◽

Safia Ogbi ◽

David M. Pollock ◽

Anne M. Dorrance

Keyword(s):

Infarct Size ◽

Cerebral Artery ◽

Mineralocorticoid Receptor ◽

Cerebral Vasculature ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Heart Study ◽

Ischemic Infarct ◽

Vessel Structure ◽

Occlusion Technique

Data from the Framingham Heart Study suggest that women may be more sensitive to the deleterious cardiovascular remodeling effects of aldosterone. Previous studies from our laboratory have shown that chronic treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist, decreases ischemic cerebral infarct size and prevents remodeling of the middle cerebral artery (MCA) in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that MR antagonism would reduce ischemic infarct size and prevent MCA remodeling in female SHRSP. Six-week-old female SHRSP were treated for 6 wk with spironolactone (25 or 50 mg·kg−1·day−1) or eplerenone (100 mg·kg−1·day−1) and compared with untreated controls. At 12 wk, cerebral ischemia was induced for 18 h using the intraluminal suture occlusion technique, or the MCA was isolated for analysis of passive structure using a pressurized arteriograph. MR antagonism had no effect on infarct size or passive MCA structure in female SHRSP. To study the potential effects of estrogen, the above experiments were repeated in bilaterally ovariectomized (OVX) female SHRSP treated with spironolactone (25 mg·kg−1·day−1). Infarct size and vessel structure in OVX SHRSP were not different from control SHRSP. Spironolactone had no effect on infarct size in OVX SHRSP. However, MCA lumen and outer diameters were increased in spironolactone-treated OVX SHRSP, suggesting an effect of estrogen. Cerebral artery MR expression, assessed by Western blotting, was increased in female, compared with male, SHRSP. These studies highlight an apparent sexual dimorphism of MR expression and activity in the cerebral vasculature from hypertensive rats.

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