Background: The purpose of this study was to examine whether there are sex differences in vasomotor responses and receptor localization of hormones and neuropeptides with relevance to migraine (vasopressin, oxytocin, estrogen, progesterone, testosterone, amylin, adrenomedullin and calcitonin gene-related peptide (CGRP)) in human intracranial arteries.
Methods: Human cortical cerebral and middle meningeal arteries were used in this study. The tissues were removed in conjunction with neurosurgery and donated with consent.
Background: Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology.
View Article and Find Full Text PDFBackground: Glioblastoma is the most common primary malignant brain tumor in adults. Previous studies have suggested that CRP (C-reactive protein) could serve as a biomarker candidate as well as a prognostic factor in glioblastoma patients, and we here further investigate its potential role.
Materials And Methods: Publicly available datasets were used to compare gene expression between brain samples from glioblastoma patients and non-tumor tissue.
Background: Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents.
View Article and Find Full Text PDFBackground: Glioblastoma is the most common and aggressive type of primary brain tumor in adults. A key problem is the capacity of glioma cells to inactivate the body's immune response. The complement system acts as a functional bridge between the innate and adaptive immune response.
View Article and Find Full Text PDFSubarachnoid hemorrhage (SAH) is most often followed by a delayed phase of cerebral ischemia which is associated with high morbidity and mortality rates. The causes underlying this delayed phase are still unsettled, but are believed to include cerebral vasospasm, cortical spreading depression, inflammatory reactions, and microthrombosis. Additionally, a large body of evidence indicates that vascular plasticity plays an important role in SAH pathophysiology, and this review aims to summarize our current knowledge on the phenotypic changes of vascular smooth muscle cells of the cerebral vasculature following SAH.
View Article and Find Full Text PDFBackground: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this study was to describe the effects of two putative VIP/PACAP receptor antagonists and the distribution of the receptor protein in rat brain vessels.
View Article and Find Full Text PDFBackground: Subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. It is suggested that the associated inflammation is mediated through activation of the mitogen-activated protein kinase (MAPK) pathway which plays a crucial role in the pathogenesis of delayed cerebral ischemia after SAH. The aim of this study was first to investigate the timecourse of altered expression of proinflammatory cytokines and matrix metalloproteinase in the cerebral arteries walls following SAH.
View Article and Find Full Text PDFBackground: Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH.
View Article and Find Full Text PDFBackground: Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture.
View Article and Find Full Text PDFCerebral ischemia that develops after subarachnoid hemorrhage (SAH) carries high morbidity and mortality. Inflammatory mediators are involved in the development of cerebral ischemia through activation of the mitogen-activated protein kinase pathway. We hypothesized that blockade of the MAPkinase/ERK (MEK)/extracellular signal-regulated kinase (ERK) pathway upstream with a specific raf inhibitor would prevent SAH-induced activation of the cerebrovascular inflammatory response.
View Article and Find Full Text PDFJ Neuroinflammation
February 2010
Background: Cerebral ischemia from middle cerebral artery wall (MCA) occlusion results in increased expression of cerebrovascular endothelin and angiotensin receptors and activation of the mitogen-activated protein kinase (MAPK) pathway, as well as reduced local cerebral blood flow and increased levels of pro-inflammatory mediators in the infarct region. In this study, we hypothesised that inhibition of the cerebrovascular inflammatory reaction with a specific MEK1/2 inhibitor (U0126) to block transcription or a combined receptor blockade would reduce infarct size and improve neurological score.
Methods: Rats were subjected to a 2-hours middle cerebral artery occlusion (MCAO) followed by reperfusion for 48 hours.
Cerebral ischemia remains the key cause of morbidity and mortality after subarachnoid hemorrhage (SAH) with a pathogenesis that is still poorly understood. The aim of the present study was to examine the involvement of thromboxane A(2) receptors (TP) in the pathophysiology of cerebral ischemia after SAH in cerebral arteries. SAH was induced in rats by injecting 250 microl of blood into the prechiasmatic cistern.
View Article and Find Full Text PDFBackground: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).
Results: Here, we found an infarct volume of 24.
Background: MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2). Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA) leading to the ischemic region. Here we explored the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126.
View Article and Find Full Text PDFEndothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries.
View Article and Find Full Text PDFCerebral ischemia results in enhanced expression of smooth muscle cell endothelin and angiotensin receptors in cerebral arteries. We hypothesise that this phenomenon may be detrimental and that acute treatment with a combined non-hypotensive dose of the angiotensin AT(1) receptor inhibitor candesartan and the endothelin ET(A) receptor antagonist ZD1611 reduces the infarct in experimental ischemic stroke. Transient middle cerebral artery occlusion was induced in male Wistar rats by the intraluminal filament technique for 2 h followed by recirculation.
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