Ligustrazine prevents basilar artery remodeling in two-kidney-two-clip renovascular hypertension rats via suppressing PI3K/Akt signaling.

OBJECTIVE: In the present study, we used a two-kidney-two-clip (2k2c) stroke-prone renovascular hypertension rat model (RHRSP) to investigate the protective effects of ligustrazine (TMP) on cerebral arteries and to examine PI3K/Akt pathway behavior under this protection. METHODS: The cerebral artery remodeling was induced by 2k2c-induced renovascular hypertension. Brain basilar artery tissues were isolated and their histological changes were detected through H&E and EVG staining, α-SMA IHC staining, and transmission electron microscopy at four, eight, and twelve weeks after 2k2c surgery, both with and without TMP treatment. Meanwhile, the ET-1, Ang II, and NO levels in basilar arteries and plasma were determined. Furthermore, the PTEN expression and the activation of PI3K/Akt in basilar artery tissues were detected through IHC and Western Blot. In addition, the primary basilar artery smooth muscle cells (BASMCs) were cultured and TMP protection of BASMCs stimulated with ET-1/Ang II in the presence or absence of insulin-like growth factor 1 (IGF-1) was determined. RESULTS: TMP attenuated basilar artery remodeling, decreased ET-1 and Ang II levels and increased NO level in basilar arteries and plasma of RHRSP rats. Moreover, TMP reduced BASMCs proliferation upon ET-1/Ang II stimulation. We also found that TMP could effectively suppress the activation of PI3K/Akt in 2k2c-RHRSP rat basilar artery and ET-1/Ang II stimulated BASMCs. Most importantly, IGF-1, as an activator of PI3K/Akt, could damage the protective effect of TMP. CONCLUSIONS: TMP exerts its protective effects and prevents basilar artery remodeling in RHRSP rats at least partly through the inhibition of PI3K/Akt pathway.

Traumatic arteriovenous fistula of the superficial temporal artery / Fístula arteriovenosa traumática de artéria temporal superficial

Arteriovenous fistulae of the superficial temporal artery are rare, and their principal cause is traumas. Complications include pulsatile mass, headache, hemorrhage and deformities that compromise esthetics. Treatment can be performed using conventional surgery or endovascular methods. The authors describe a case of a 44-year-old male patient who developed a large pulsating mass, extending from the preauricular region to the right parietotemporal and frontal regions after a motorcycle accident. The treatment chosen was complete surgical removal of the pulsatile mass and ligature of the vessels feeding the fistula.

As fístulas arteriovenosas de artéria temporal superficial são raras, sendo o trauma sua etiologia principal. Suas complicações incluem massa pulsátil, cefaleia, hemorragia e deformidade estética. O tratamento pode ser realizado por cirurgia convencional ou endovascular. Os autores relatam o caso de um paciente de 44 anos que evoluiu com massa pulsátil extensa desde região pré-auricular até região parietotemporal e frontal direita após acidente motociclístico. Optou-se por remoção cirúrgica completa da massa pulsátil e ligadura dos vasos nutridores da fístula.

Generalized arteriopathy in patients with cervical artery dissection.

OBJECTIVE: To make an ultrastructural comparison of superficial temporal artery (STA) biopsy specimens from patients with spontaneous cervical artery dissection (sCAD) and controls. METHODS: The authors used light microscopic examination of semithin sections and electron microscopic examination of ultrathin sections of STA biopsy specimens from patients with sCAD and controls. RESULTS: STA biopsy specimens from patients with sCAD taken around the time of the dissection showed a zone of connective tissue weakening with fissuring at the junction between the tunica media (TM) and the tunica adventitia (TA) in seven of nine specimens and erythrocyte infiltration in eight of nine specimens but in none of the control specimens. Light microscopy demonstrated transparent circular spots that, on electron microscopy, turned out to represent erythrocytes and other cellular components at different stages of degradation. Occasionally, scattered immune cells were found in specimens from patients with sCAD. In addition, smooth muscle cells of the synthetic phenotype, some of them showing extensive vacuolation were more common in the TM of STA biopsy specimens from patients with sCAD than in control specimens. CONCLUSIONS: Signs of tissue weakening along the TM/TA junction in STA biopsy specimens of patients with sCAD but not in controls suggest the presence of a generalized arteriopathy leading to impairment of the stability of the arterial wall in patients with sCAD. Limiting factors of the study are that some control biopsies were obtained from autopsies and that the anticoagulation status of patients and controls were not completely comparable.

Medin and medin-amyloid in ageing inflamed and non-inflamed temporal arteries.

Small amyloid deposits commonly occur along the internal elastic lamina of the temporal artery. In temporal artery biopsies from 22 patients with histological signs of giant cell arteritis and 25 without, amyloid deposits were found in 14 and 21 biopsies, respectively. Two specific peptide antisera show that this amyloid is identical to the recently identified medin-amyloid in the ageing aorta. On immunoelectron microscopy, the amyloid appeared topographically closely related to the elastic material. Furthermore, fragmented elastic material was often immunolabelled for medin and found to be engulfed by giant cells. Medin is an internal fragment of the larger precursor lactadherin and is presumably formed by specific enzymatic cleavage events. In situ hybridization showed that lactadherin is expressed locally by smooth muscle cells of the temporal artery. Given the potential role of lactadherin as a mediator for the adhesion of cells, including macrophages, to other cells or surfaces, lactadherin or its fragment medin may be important in the inflammatory process in giant cell arteritis.

Detection of varicella zoster virus DNA in some patients with giant cell arteritis.

PURPOSE: The purpose of this study was to determine whether an association exists between giant cell arteritis (GCA) and the presence of varicella-zoster virus (VZV), by using histologic, molecular, immunohistochemical, and ultrastructural analyses of temporal artery biopsy specimens. METHODS: In a randomized masked study, 64 temporal artery biopsy specimens were analyzed by PCR for VZV DNA. The samples included 35 specimens histologically positive and 29 specimens histologically negative for GCA. Immunohistochemical staining for VZV viral antigen IE-63 was performed on seven of the specimens positive for GCA and five negative specimens. Transmission electron microscopy (TEM) was performed on five of the specimens positive for GCA. RESULTS: PCR was positive for VZV DNA in 9 (26%) temporal arteries tested that showed histologic evidence of GCA. The remaining 26 histologically positive temporal arteries and all 29 histologically negative arteries tested gave negative PCR results for VZV DNA. Statistical analysis (z-test) comparing the association of VZV DNA between the specimens that were positive and negative for GCA showed a significant difference (P = 0.010). Immunohistochemical studies were positive in several biopsy specimens within adventitial histiocytes-macrophages, but these results did not correlate with either the presence or absence of VZV DNA or with the histologic evidence of GCA. No viral particles were observed by TEM. CONCLUSIONS: This study showed a significant association of VZV DNA to temporal artery biopsy samples positive for GCA compared with the negative specimens. The results support the hypothesis that VZV may play a role in the pathogenesis of some cases of GCA. However, PCR, immunohistochemical, and electron microscopic findings suggest the virus is present at extremely low quantities, is abortively replicating, or is latent.

The blood supply of the human temporalis muscle: a vascular corrosion cast study.

Knowledge as to the blood supply of the human temporalis muscle is limited to its extramuscular path and relations, little information existing about the intramuscular vascular architecture. To investigate the 3-dimensional vascular network in the human temporalis muscle, in 5 fresh cadavers an infusion of methylmethacrylate resin was made via the carotid vessels with subsequent removal of the organic tissues by a corrosion process. The vascular corrosion casts of the temporalis muscle were studied by stereomicroscopy and scanning electron microscopy. In 6 well perfused muscle specimens, the temporalis muscle was found to be consistently supplied by 3 arteries: the anterior and posterior deep temporal arteries, and the middle temporal artery. Each primary artery branched into the secondary arterioles and then terminal arterioles. The venous network accompanied the arteries, and double veins pairing a single artery was a common finding. Arteriovenous anastomosis was absent, whereas arterioarterial and venovenous anastomoses were common. The capillaries formed a dense interlacing network with an orientation along the muscle fibres. Understanding of the intramuscular angioarchitecture of the temporalis provides the vascular basis for surgical flap manipulation and splitting design.

[Non-giant cell temporal arteritis as a manifestation of Churg-Strauss syndrome. Presentation of a case and review of literature]. / Arteritis no de células gigantes de la temporal como manifestación clínica del síndrome de Churg-Strauss. Presentación de un caso y revisión de la literatura.

Most cases of temporal arteritis are of the giant cell variety, with cases involving other histologic patterns occurring rarely. There are only 4 descriptions in the literature of non giant cell temporal arteritis as a manifestation of Churg-Strauss syndrome. We report the case of a 74-year-old man with a history of bronchial asthma who presented with systemic symptoms and right temporal cephalea with diplopia, diffuse muscle pain and transient skin lesions on the extremities. The right temporal artery was enlarged and painful but pulsatile. Tests showed a high erythrocyte sedimentation rate and leukocytosis with relative and absolute eosinophilia. Biopsy of the temporal artery revealed polymorphic inflammatory infiltration throughout the vas, with numerous eosinophils and non giant cells, confirming a diagnosis of Churg-Strauss syndrome with extension to the temporal artery. Temporal arteritis should be considered a syndrome with variable substrate pathology; the possibility that it is a rare manifestation of systemic necrotizing vasculitis should not be ruled out.

Ultrastructural localization and translocation of nitric oxide synthase in the endothelium of the human cerebral artery.

An electron microscopic immunocytochemical study was undertaken to clarify ultrastructural localization and translocation of nitric oxide synthase (NOS) in endothelial cells (EC) of the human cerebral and superficial temporal arteries (STA) employing antibody against endothelial NOS (EC-NOS). NOS immunoreactivity was found in all EC examined, in association with the plasma membrane and cytoplasmic organelles such as endoplasmic reticulum, Weibel-Palade body and subplasmalemmal vesicles, and in the cytoplasm devoid of organelles and extracellular regions, irrespective of arteries. The immunoreactivity in subplasmalemmal vesicles was, however, demonstrated only in human cerebral arteries. In the human STA exposed to bradykinin which induces EC-NOS phosphorylation, the gold particles significantly increased in the cytosol and decreased in the areas associated with cytoplasmic organelles; however, the number of particles did not change significantly in the plasma membrane. The results implicate that NOS may be translocated from the area associated with cytoplasmic organelles to cytosol following EC exposure to bradykinin.

The angioarchitecture of the rat mandibular joint bilaminar zone.

In mammals, temporomandibular-joint articular disc attachments have a bilaminar pattern. The three-dimensional angioarchitecture of the bilaminar zone in the adult rat was described using scanning election microscopy of microvascular corrosion casts (47 specimens) and light microscopy of Indian ink-injected, cleared, thick-sectioned temporomandibular joints (6 specimens). The bilaminar zone had an axial core of feeder vessels composed primarily of flat venules which were organized in plexuses. Arterioles were few and slender. In both laminae, there were usually three branching levels until vessels approached the surface of the lamina, where a dense capillary meshwork was formed. Both laminae ended abruptly at the periphery of the avascular disc with a single, slightly undulating marginal vessel. This marginal vessel, which faced the avascular disc, was definitely larger in diameter than the other superficial capillaries and was rather a postcapillary venule than a capillary. Functionally, this marginal venule might be important in sustaining nutrition of the avascular disc centre by allowing bidirectional blood flow during jaw movements.

The peptidergic innervation of the human superficial temporal artery: immunohistochemistry, ultrastructure, and vasomotility.

The peptidergic innervation of the human superficial temporal artery was investigated by means of immunohistochemical, ultrastructural, and in vitro pharmacological techniques. A dense network of nerve fibers was found in the adventitia. The majority of the nerve fibers displayed immunoreactivity for tyrosine hydroxylase and neuropeptide Y (NPY). A moderate supply of perivascular nerve fibers displayed either acetylcholinesterase activity or immunoreactivity for vasoactive intestinal peptide (VIP), peptide histidine methionine-27 (PHM), and calcitonin gene-related peptide (CGRP). Only a few nerve fibers displayed substance P (SP), neurokinin A (NKA), and neuropeptide K (NPK) immunoreactivity. In double immunostained preparations, SP immunoreactivity was co-localized with NPK and CGRP in the same nerve fibers. Ultrastructural studies revealed the presence of numerous axon variocosities at the adventitial--medial border. NPY, VIP, and CGRP immunoreactivities occurred in the same type of large granular vesicles, but in morphological distinct nerve profiles. NPY had, in general, no direct vasoconstrictor effect. However, at a low concentration of NPY contractile response induced by NA (10(-7)-10(-6)M) was 9-15 times enhanced. The NPY-induced potentiation of the NA-induced contraction was not dependent on the presence of an intact endothelium. No significant difference was found between acetylcholine, VIP, and PHM in either potency or degree of relaxation. SP, NKA, and CGRP also acted as vasodilatory agents, with CGRP being more potent than the tachykinins. The response to SP, but not CGRP, was dependent on an intact endothelium. Pretreatment of the vessels with a low concentration of NPY did not change the responses to ACh, VIP, SP, or CGRP.

5-Hydroxytryptamine receptor characterization of human cerebral, middle meningeal and temporal arteries: regional differences.

We have studied the regional distribution of 5-hydroxytryptamine (5-HT) receptor subtypes in fresh circular segments of human cerebral, middle meningeal, and temporal arteries. Vasomotor responses induced by a series of 5-HT agonists and antagonists with some degree of selectivity were studied by using a sensitive in vitro system. Nine 5-HT agonists were examined for contractile effects on the arteries. In cerebral and meningeal arteries 5-carboxamidotryptamine (5-CT) was more potent than 5-HT. The opposite order of potency (5-HT-5-CT) was found in temporal arteries. In the cerebral arteries 5-methoxytryptamine (5-MeOHT) was more potent than sumatriptan while sumatriptan was more potent than 5-MeOHT in meningeal and temporal arteries. The 5-HT1 receptor antagonist, methiothepin, competitively antagonized 5-CT-induced contractions in cerebral arteries, with a pA2 value of 9.05. 5-HT-induced contractions were competitively antagonized by ketanserin (5-HT2) in the temporal arteries pA2 value of 9.06). Methiothepin and ketanserin had non-competitive antagonistic effects in the middle meningeal arteries. The 5-HT3 selective antagonist ondansetron did not cause any shift of the contractions induced by 2-methyl-5-HT in the temporal, cerebral and middle meningeal arteries. These results suggest that the cerebral arteries mainly contain 5-HT1D or 5-HT1-like receptors, and the temporal artery 5-HT2 receptors; the data further indicate the presence of both receptor subtypes in the middle meningeal artery.

Senile aortic amyloid. Evidence for two distinct forms of localized deposits.

Aortic tissues obtained at autopsy were examined from 84 patients (age, 18-96 years). Amyloid deposits were present in the media in 61 of 63 (97%) of the patients above the age of 50. In addition, intimal amyloid deposits were present in 35% of this group. Intimal amyloid differed from medial amyloid both in its morphologic characteristics and its association with atherosclerosis. An antiserum raised to a low molecular weight protein extracted from amyloid fibrils of the aortic media reacted specifically with medial amyloid but did not react with intimal deposits. Neither type of amyloid reacted with anti-ATTR (Senile systemic amyloid), anti-AANF (isolated atrial amyloid), or antisera to other known forms of amyloid. These findings are consistent with the presence of two separate forms of localized amyloid in the aging aorta.

A histological, ultrastructural and immunohistochemical study of superficial temporal arteries and middle meningeal arteries in moyamoya disease.

Pathologic changes in superficial temporal arteries (STA) and middle meningeal arteries (MMA) biopsied from 15 patients with moyamoya disease (MD) who had undergone cerebro-temporal arterio-synangiosis were studied histologically, ultrastructurally and immunohistochemically. The main pathologic features were: proliferation of smooth muscle cells (SMCs) and thickening of the intima, degeneration and destruction of SMCs in the media and intima, and the presence of condensed organelles in necrosed SMCs or the interstitium among SMCs, or both outside and within the elastica interna (EI). The EI had become thin, porous, fragmented and was even absent in some segments. These changes are different from those of other forms of angiopathy, but identical with those at the ends of internal carotid arteries (ICA) reported by us previously, being pathognomonic for MD. These changes in the STA and MMA reveal that MD involves not only the ICA but also the intra- and extracranial branches of external carotid arteries. The medial necrosis of SMCs seems to be the primary injury of the arterial wall in MD. STA tissue blocks from two cases of MD were stained immunohistochemically. By electron microscopy, IgG-, IgM-, and C3-positive granules were observed on the ER of endothelial and intimal cells. Further studies on more cases are needed to determine whether an immunoreaction has occurred in these arteries.

[Morphologic changes in the skin and superficial temporal arteries in Sneddon's syndrome]. / Morfologicheskie izmeneniia v kozhe i poverkhnostnykh visochnykh arteriiakh pri sindrome Sneddona.

Skin biopsies from livedo's areas of 25 patients and fragments of superficial temporal arteries of 10 patients with Sneddon's syndrome were examined. Pathological changes in the dermis arteries of small and medium calibers were found in the form of the intima hyperplasia, proliferation of vascular wall cell elements (80%), arterial thrombosis (with diameter of 60-200 microns). These changes were found in 68% of observations when clinical and morphological signs of vasculitis were lacking. "Arteriopathy" is the most appropriate term for such lesions. Focal and diffuse fibro-muscular elastic hyperplasia of the intima and muscular layer fibrosis in the wall of superficial temporal arteries may be considered as age-associated lesions. Ultrastructurally, a selective damage of the non-adrenergic part of the nervous apparatus of the dermal arteries and superficial temporal arteries were observed; this suggests the participation of the damaged vascular neurogenic regulation in the formation of organic vascular changes.

Cluster headache: ultrastructural evidence for mast cell degranulation and interaction with nerve fibres in the human temporal artery.

It has been suggested that histamine plays an important role in the pathogenesis of cluster headache. In addition, both neurogenic and vascular components have been described during cluster headache attacks without an obvious anatomical link between them. Our ultrastructural observations of human temporal arteries from cluster headache patients and their comparison to those from a control group strongly suggest that mast cells may be this link. Mast cells in both groups show a very close apposition with nerve fibres, suggesting a functional interaction between them. Moreover, in the cluster headache group exclusively, adventitial mast cells show profound morphological modifications suggesting progressive degranulation. These data strongly suggest that mast cells could be directly or indirectly involved in the pathophysiology of cluster headaches.

Scanning electron microscopy as a diagnostic procedure in giant cell arteritis.

Forty-five consecutive patients (32 women and 13 men) underwent biopsy of the temporal artery because of suspected giant cell arteritis. Their ages ranged from 38 to 84 years, mean 68.1 years. Five patients (11.1%) four of them women, were found to be affected by the disease. Their ages ranged from 54 to 80 years, mean 69 years. Clinical and laboratory findings included elevated erythrocyte sedimentation rate, prolonged fever, continuous headache, sudden onset of unilateral blindness, intermittent mandibular claudication, severe anemia and myalgia. None of these, whether present in isolation or in various combinations, were of significant diagnostic value. All biopsies were examined both by light microscopy and by scanning electron microscopy. The former examination took about 5-7 days to complete, and the latter about 3 hours. Light microscopy studies showed that 46.6% of the arterial biopsies were normal, 42.3% were arteriosclerotic and 11.1% (5 specimens) were characteristic of giant cell arteritis. Scanning electron microscopy revealed that the biopsies obtained from all five patients found to have temporal arteritis displayed the "occlusive" pattern: the three-laminar appearance of the artery was markedly distorted or lost, the internal elastic lamina was barely detectable, and the densely hypertrophied media and intima filled the arterial lumen, virtually obliterating it. We conclude that scanning electron microscopy is a quick and accurate procedure for diagnosis of temporal arteritis and that positive findings may be taken as an indication for immediate steroid treatment.

[Electron microscopy findings of the superficial temporal artery and the middle cerebral artery in patients with vascular diseases]. / Elektronenmikroskopische Befunde an den Arteriae temporalis superficialis und cerebri media bei Patienten mit Gefässerkrankungen.

Tissue samples taken from the A. cerebri media and A. temporalis superficialis were examined via electron microscope in 52 patients surgically treated by applying an externa-interna anastomosis. The findings are described.

[Does the direct immunofluorescence examination of superficial temporal artery biopsies have any value? Results of the study of 101 biopsies]. / L'examen en immunofluorescence directe des biopsies d'artères temporales superficielles présente-t-il un intérêt? Résultats de l'étude de 101 biopsies.

The lesions in temporal arteritis (TA) are known to be often segmental and the pathologic study of involved temporal arteries may be falsely negative. Several reports suggest that direct immunofluorescence (IF) may be of value in the diagnosis of the disease. We have studied by IF 101 consecutive biopsies from 100 patients investigated during the last two years. Adjacent segments were processed for light and immunofluorescent microscopy. For the latter, tissues were immediately frozen in liquid nitrogen and stored at -- 70 degrees C. Cryostat sections were stained with anti-gamma, alpha, mu, C3, fibrinogen and albumin conjugates. A sister section was also stained with HE for light microscopy. Deposits of Ig and/or C were either granular (intra- or extra-cellular) or linear closely applied to internal elastic lamina. The 100 patients fall into 4 groups: Group I, (19 patients) with diagnosis ascertained upon typical clinical record and clear cut anatomic lesions by light microscopy; Group II (10 patients) with the clinical features of TA and a negative biopsy by light microscopy; Group III (29 patients) in whom the diagnostic criteria of polymyalgia rheumatica were fulfilled according to Forestier and Certonciny; Group IV (42 patients) affected with various diseases unrelated to T.A. (1 with polyarteritis nodosa, 5 with rheumatoid arthritis...). The following results were obtained by IF: in group I, deposits were found in 63% of the patients studied (linear in 11 and granular in 4 cases). They included Ig usually with C3 and fibrinogen. In group II, we observed linear deposits of IgG in one patient and granular C3 deposits in another case.(ABSTRACT TRUNCATED AT 250 WORDS)