Human Cerebral Blood Vessels Research Articles

Sympathetic Nervous System Moves Toward Center Stage in Cardiovascular Medicine

In 1664, the first anatomically correct depiction of the sympathetic nervous system came from Thomas Willis and his circle of London anatomists,1 included in The Anatomy of the Brain and Nerves , 1664 (Figure 1). This, the first work dedicated completely to the nervous system, also described the arterial loops at the base of the brain, which we now know as the Circle of Willis.1 Christopher Wren, an anatomist member of the group, was the principal illustrator1 before being asked by the City Fathers to turn his talents to town planning, architecture, and cathedral building after the 1666 Great Fire of London. Figure 1. An illustration of the human sympathetic nerves of the neck and thorax, from The Anatomy of the Brain and Sympathetic Nerves , published in 1664 by Thomas Willis and reproduced in Soul Made Flesh .1 Almost 2 centuries later, subsequent microscopic examination demonstrated that blood vessel walls were densely innervated, leading Stelling in 18402 to correctly conclude that these vasomotor fibers were in fact sympathetic nerves that were carried from the central nervous system to the blood vessels. In the mid-19th century, celebrated European physiologists, including Brown-Sequard, Waller, and Bernard,2 built on these observations, demonstrating vasoconstriction with electrical stimulation of the cut nerves and vasodilatation on nerve section, which indicated that the sympathetic fibers exerted a tonic, vasoconstrictor influence. The pressor nerves had gained recognition. Identification of the sympathetic neurotransmitter proved to be difficult. Claims for epinephrine3,4 and the hypothetical sympathins I and E confused the picture. Ulf von Euler compared bioassay responses of epinephrine, norepinephrine, and dihydroxy norephedrine with those of cattle splenic nerve extract, by testing blood pressure (BP) responses in the anesthetized cat and contractile responses in the isolated pregnant rabbit uterus, to definitively demonstrate the …

Tachyphylaxis to the Sumatriptan-Induced Contractile Effect in the Human Uterine Artery but Not in Human Cerebral Blood Vessels: Pharmacological Demonstration of the 5-HT1B Receptor Functionality Loss

The in vitro contractile response of the human uterine artery to sumatriptan was compared to that of human cerebral blood vessels. Artery rings were prepared for isometric contraction. Tachyphylaxis to the triptan-induced vascular contraction was observed in the uterine artery, but not in basilar and middle cerebral arteries. To evaluate 5-HT₁ receptor subtypes functionality, concentration-response curves to sumatriptan were performed at 0 and 24 h after uterine artery isolation. Both 10 µmol/l cyanopindolol and 63 nmol/l SB 224,289 (5-HT_1B receptor antagonists) significantly antagonized the contractile response induced by sumatriptan at 0 h but not after 24 h of uterine artery isolation. The 5-HT_1B/1D receptor antagonist BRL 15,572 at 10 µmol/l significantly antagonized the sumatriptan contractile response at both experimental conditions. We conclude that the tachyphylaxis to sumatriptan observed in the non-cerebral blood vessels, and not in the cerebral ones, may be due to loss of functionality of the 5-HT_1B receptor subtype, increasing the safety of triptans.

Balloon catheterization

✓ A balloon catheter technique for catheterization of human cerebral blood vessels is described. Temporary occlusion of different cerebral vessels was successfully accomplished in more than 300 cases, including investigations of collateral blood flow, intraarterial pressure, brain temperature, the vital staining of tumors, and the introduction of chemical agents. Temporary occlusion of the internal carotid artery makes possible angiography of the external carotid, while occlusion of separate branches of the external carotid permits selective angiography of its functioning branches. The balloon catheter is valuable in investigating arteriovenous and carotid-cavernous fistulas. With the help of a detachable balloon it is possible to occlude the cavity of arterial aneurysms or the afferent vessels of arteriovenous aneurysms; it is also useful as a means to shut off the blood flow to arterial aneurysms and carotid-cavernous fistulas when access is difficult. A method for reconstruction of the cavernous part o...

Significance of source and size in the mechanical response of human cerebral blood vessels

Cerebral blood vessels are frequently damaged in traumatic brain injury. Mechanical properties of fresh human cerebral vessels obtained through surgeries have been reported. Because surgical sources of human specimens are rare and produce a limited amount of material, we sought to compare the properties of more readily available cerebral arteries and veins obtained from cadavers to fresh vessel data. Additionally, because the previous study was limited to small vessels available in surgery, it was unknown how generally applicable the results were to larger cerebral arteries and veins. In the current study, large and small cerebral vessels from autopsy were stretched axially. Data from these and similar tests on fresh vessels were combined to determine the significance of source and size on mechanical properties. Structural comparisons of histological samples were additionally utilized to characterize differences. Results indicate that specimens from autopsy and surgery behave similarly except that vessels from autopsy tend to be less extensible. While tests on large vessels were limited, small arteries obtained from autopsy tended to be slightly stiffer than large arteries. In contrast, bridging veins from cadavers were typically stiffer and stretched less before structural failure than cortical veins from the same source. These effects are, however, secondary to differences identified between arteries and veins in the previous study.

Nociceptin immunoreactivity and receptor mRNA in the human trigeminal ganglion

Nociceptin is a peptide transmitter belonging to the opioid family. Nociceptin has recently attracted considerable interest since it appears to exhibit a number of differences to the other opioids. In the present study, we used a nociceptin antibody to map the distribution of nociceptin in the human trigeminal ganglion. In addition, we studied the nociceptin receptor at mRNA levels by RT–PCR and the vasomotor response to nociceptin in human cerebral vessels using a sensitive in vitro method. About 70% of all neuronal cells in trigeminal ganglia were nociceptin immunopositive. Nociceptin was predominantly (78%) expressed in medium-sized cells (30–60 μm). Nociceptin also distributed in small-sized cells (14% of positive cell bodies; <30 μm) and in large-sized cells (8% of positive cell bodies; >60 μm). Double immunostaining showed that in the human trigeminal ganglion nociceptin colocalized with calcitonin gene-related peptide (CGRP), substance P (SP), nitric oxide synthase (NOS) or pituitary adenylate cyclase activating peptide (PACAP). About 61% of nociceptin positive cells contained CGRP, 54% contained SP, 50% contained NOS and 68% contained PACAP. Immunoreactivity to nociceptin was not detected in human cerebral blood vessels. Reverse transcriptase–polymerase chain reaction detected the expression of nociceptin receptor mRNA in trigeminal ganglia but not in basilar arteries. To further examine whether there are functional nociceptin receptors in human cerebral arteries, a pharmacological study was done, where cerebral arteries revealed strong contractions to 60 mM K + and U466166 and strong relaxation to CGRP. Nociceptin failed to elicit contraction or relaxation. In conclusion, nociceptin is expressed in human trigeminal ganglia but not in cerebral blood vessels. Nociceptin is colocalized with CGRP, SP, NOS and PACAP. Nociceptin receptor mRNA is expressed in human trigeminal ganglia but not in basilar arteries. The functional role of nociceptin may be at the presynaptic level.

Expression of α-synuclein, the precursor of non-amyloid β component of Alzheimer's disease amyloid, in human cerebral blood vessels

The non-amyloid β component of Alzheimer's disease amyloid (NAC) is detected in cerebral amyloid angiopathy; and the precursor of NAC is now known to be identical to α-synuclein (α-S), a major component of Lewy bodies in Parkinson's disease. We studied if cerebral vascular cells express α-S. Immunohistochemical studies of human cerebral tissues from control and cerebral amyloid angiopathy patients revealed the expression of α-S in vascular endothelial and smooth muscle cells. Then we studied the expression of α-S in vitro using cultures of vascular cells. Cultures of human umbilical vein endothelial cells and umbilical artery smooth muscle cells were found to constitutively express α-S messenger RNA and protein. α-S is normally expressed in vascular cells and may play some physiological role in the vascular wall.

Peptidergic innervation of human cerebral blood vessels and saccular aneurysms.

Peptidergic innervation of the human cerebral vasculature has not yet been described in detail and its role in the maintenance of cerebral autoregulation still needs to be established. Similarly, few data exist on the innervation of vascular malformations. The aim of this study was to clarify the peptidergic innervation patterns of human cerebral arteries of various sizes, and, for the first time, that of saccular aneurysms. Light microscopic study of whole-mount preparations of human cerebral arteries and aneurysm sacs resected either during tumor removal or after neck-clipping were carried out by means of silver-intensified light microscopic immunocytochemistry visualizing neuropeptide-Y, calcitonin gene-related peptide and substance P immunoreactivity. Systematic morphological investigations confirmed the presence of longitudinal fiber bundles on the adventitia and a network-like deeper peptidergic system at the adventitia-media border, while in smaller pial and intraparenchymal vessels, only sparse longitudinal immunopositive axons could be detected. The innervation pattern was totally absent in the wall of saccular aneurysms with the complete disappearance of peptidergic nerve fibers in some areas. To the best of our knowledge neither the disappearance of this network on small pial and intraparenchymal vessels, nor the absence of an innervation pattern in saccular aneurysms have been described before. Nonhomogeneous peptidergic innervation of the human cerebral vascular tree might be one of the factors responsible for the distinct autoregulatory properties of the capacitance and resistance vessels. Malfunction of this vasoregulatory system might lead to the impairment of autoregulation during pathological conditions such as subarachnoid hemorrhage.

Expression of calcitonin gene-related peptide 1 receptor mRNA in human trigeminal ganglia and cerebral arteries

Reverse transcriptase polymerase chain reaction (RT-PCR) using primers for the recently cloned human CGRP 1 receptor detected mRNA expression of CGRP 1 receptors in trigeminal ganglia and cerebral vessels, obtained at autopsy or during neurosurgical tumor resections. An RT-PCR product of the expected size (339 bp) was seen in cerebral arteries, both in the presence and in the absence of endothelium and in trigeminal ganglia. Sequence analysis of the RT-PCR product of the published sequence showed 100% homology with the human CGRP 1 receptor. The presence of the CGRP 1 receptor mRNA in human trigeminal ganglia and cerebral blood vessels, indicates the occurrence of both prejunctional (trigeminal) and postjunctional location (blood vessels) of the CGRP 1 receptor.

Nerve growth factor concentrations in human cerebral blood vessels.

The distribution of glutamate-like immunoreactivity (Glu-LI) in the thalamic ventral posterolateral nucleus (VPL) of cats was studied with the EM immunogold technique in order to identify nerve terminal populations that...

Human cerebrovascular nerve fibers immunoreactive for synaptophysin, chromogranin A and tyrosine hydroxylase

The innervation of human cerebral blood vessels has been examined using synaptophysin, a marker of synaptic vesicles, and chromogranin A, a marker of large dense-core vesicles. The catecholaminergic marker tyrosine hydroxylase was used for comparison. Synaptophysin and tyrosine hydroxylase demonstrated a similar distribution of nerve fibers whereas chromogranin A terminals were only sparsely evident. Our results suggest that there is not a subset of nerve fibers in existence which has a distribution different than that of catecholaminergic fibers. Furthermore, in view of its unexpected sparse distribution, chromogranin A in the nervi vasorum is not likely to be a significant contributor to cerebral blood flow regulation.

The identification of adrenergic receptors in human pial membranes

Recent experimental work has suggested that the adrenergic nervous system is important in regulating cerebral blood flow under conditions of hypoxia and systemic arterial hypertension. Although previous investigations have demonstrated the presence of adrenergic neurons adjacent to human cerebral vessels, the nature of adrenergic receptors on human cerebral blood vessels remains poorly defined. The present study was performed to characterize adrenergic reception on membranes prepared from human pia, a rich source of small blood vessels, using radioligand binding techniques. Adrenergic membrane receptors were characterized using the binding of [3H]dihydroalprenolol for the beta subtypes and [3H]prazosin and [3H]yohimbine for the alpha subtypes. Displaceable binding was demonstrated with each agent. A small series of adrenergic agents competed for the [3H]dihydroalprenolol, [3H]yohimbine, and [3H]praz binding sites in a fashion suggesting the presence of alpha 1-, alpha 2-, beta 1-, and beta 2-receptors on the vessels within human pia.

The Identification of Adrenergic Receptors in Human Pial Membranes

Abstract Recent experimental work has suggested that the adrenergic nervous system is important in regulating cerebral blood flow under conditions of hypoxia and systemic arterial hypertension. Although previous investigations have demonstrated the presence of adrenergic neurons adjacent to human cerebral vessels, the nature of adrenergic receptors on human cerebral blood vessels remains poorly defined. The present study was performed to characterize adrenergic reception on membranes prepared from human pia, a rich source of small blood vessels, using radioligand binding techniques. Adrenergic membrane receptors were characterized using the binding of [3H]dihydroalprenolol for the B subtypes and [3H]prazosin and [3H]yohimbine for the A subtypes. Displaceable binding was demonstrated with each agent. A small series of adrenergic agents competed for the [3H]dihydroalprenolol, [3H]yohimbine, and [3H]praz binding sites in a fashion suggesting the presence of A1-, A2-, B1and B2-receptors on the vessels within human pia.

Cholinergic innervation of vasopressin-containing cells of human cerebral blood vessels

Cholinergic innervation of vasopressin-containing cells of human cerebral blood vessels

Use of human post-mortem cerebral blood vessels to study vasospasm

Although it is a major cause of death in patients with subarachnoid haemorrhage, little is known about the mechanisms involved in cerebral vasospasm. This is due to the difficulty in obtaining human tissue, and to wide differences between species in the response to vasoactive compounds. In this review, Karsten Schrör and Raphaela Verheggen discuss the evidence that the response of human cerebral blood vessels changes little during the first 24 h after death, and argue that samples obtained post-mortem provide a suitable model system to study vasospasm in vitro.

Balloon catheterization and occlusion of major cerebral vessels.

✓ A balloon catheter technique for catheterization of human cerebral blood vessels is described. Temporary occlusion of different cerebral vessels was successfully accomplished in more than 300 cases, including investigations of collateral blood flow, intraarterial pressure, brain temperature, the vital staining of tumors, and the introduction of chemical agents. Temporary occlusion of the internal carotid artery makes possible angiography of the external carotid, while occlusion of separate branches of the external carotid permits selective angiography of its functioning branches. The balloon catheter is valuable in investigating arteriovenous and carotid-cavernous fistulas. With the help of a detachable balloon it is possible to occlude the cavity of arterial aneurysms or the afferent vessels of arteriovenous aneurysms; it is also useful as a means to shut off the blood flow to arterial aneurysms and carotid-cavernous fistulas when access is difficult. A method for reconstruction of the cavernous part of the carotid artery in cases of carotid-cavernous fistulas is described.

X-ray microscopy and histochemistry of the human cerebral blood vessels

Differential injection with radiopaque materials followed by projection x-ray microscopy has demonstrated the microangiographic pattern of epicerebral, transcerebral, and cortical blood vessels in the human brain. The authors report that alkaline phosphatase activity provides a means of showing the capillary bed more completely and differentiating cortical arteries from cortical veins. The vertical and horizontal organization of the cortical vessels is related to the cortical columns and lamination. Pairing and spiraling of arterioles of the penetrating cortical vessels are described. Lead staining for neuronal acid phosphatase activity in combination with alkaline phosphatase stain for blood vessels makes it possible to examine the neurons and microvascular pattern by both optical and projection x-ray microscopy.

Studies in cerebral circulation. Methods for the qualitative and quantitative study of human cerebral blood vessels

Injection of 138 normal and pathologic human brains has led to the development of standardized methods for the comprehensive study of cerebral blood vessels. A device for the rapid parallel sectioning of the whole human brain at 1 to 5 mm. is described. Modified x-ray techniques are presented which provide for the stereoscopic study of intracerebral arteries and veins without destruction of the specimen or alteration of staining properties. Procedures for the quantitative study of capillary angioarchitecture in normal and pathologic brains are presented, and methods for the differential study of vascularity in absolute terms are described. Preliminary observations are used as illustrations.