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.

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.

[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.

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.

[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.

[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)

[Electron microscopic and immunohistologic studies of patients with Horton's temporal arteritis]. / Elektronenmikroskopische und immunhistologische Untersuchungen bei Patienten mit Arteriitis temporalis Horton.

Temporal arteritis is a systmic disease with a predilecation for the cranio-temporal vascular area. Histologically it is a panarteritis. Diagnosis is based on the presence of lymphocytes, histiocytes and foci of epitheloid cells in the media of the temporal artery. The presence of giant cells is, however not obligatory. The present study emphasizes the value of biopsy of the temporal artery in diagnosing this disease. It, furthermore, also points out the 10-percent possibility of false negative biopsy results based on patchy vascular lesions. Tenderness to touch of the temporal artery, characteristic of temporal arteriitis, can be explained by perineural inflammatory infiltration of nerves in the adventitia of this artery. Examination under the electron microscope reveals almost complete destruction of the smooth muscles of the media by epitheloid cell granulomas. Massive neogenesis of collagen ensues. Furthermore, numerous myofibroblasts, macrophages and histiocytes are observed. Several macrophages close to each other create the impression of giant cells in the light microscope. The electron microscope image allows for clear differentiation between temporal arteritis on one hand and of arteriosclerosis on the other. Using the immunoperoxidase method in temporal arteritis, immune globulines are found intracellularly in plasma cells. Extracellularly, however, neither immune golbulins nor complement deposits are found in the vascular wall. Thus, the assumption that temporal arteritis represents a immune complex disorder cannot be maintained. The most frequent ophthalmologic complication in temporal arteritis is ischemic optic neuropathy. Histologic examination of a bulbus presenting anterior ischemic optic neuropathy in a case of temporal arteritis revealed predominantly lymphocytic infiltrations of the short and long ciliary arteries. No inflammatory infiltration was found in the central retinal artery. The development of anterior ischemic optic neuropathy can be explained by impaired perfusion or by occlusion of the short posterior ciliary arteries. In 60% of patients suffering from temporal arteritis, we found anticollagen antibodies in the serum. Collagenization of the vascular wall as observed in our electron-microscopic examinations must, therefore, be considered the paradoxical consequence of an immune reaction caused by collagen auto-antibodies. Collagen auto-antibodies play a decisive role in the maintenance and chronicity of the inflammatory process in temporal arteritis. In therapy, corticosteroids should not be administered according to rule but rather in doses adjusted to individual requirements.(ABSTRACT TRUNCATED AT 400 WORDS)

Histologic and ultrastructural characteristics of temporal arteritis. The value of the temporal artery biopsy.

Temporal artery biopsy is an easily performed procedure of low morbidity that produces valuable information in establishing a diagnosis and guiding therapy as well as providing tissue for further pathologic and immunologic research aimed at understanding and ultimately controlling this disease. The pathogenesis of temporal arteritis remains unresolved. In an effort to clarify this question, 19 temporal arteries demonstrating typical arteritic changes by light microscopy were also examined by transmission electron microscopy. At the light microscopic level, a granulomatous inflammation, often containing giant cells, was found in all layers of the vessel but most commonly concentrated within the internal or external border of the muscular media. The internal elastic lamina was usually fragmented and surrounded by inflammatory cells. Segmented subintimal fibromuscular hyperplasia and lymphocytic and plasma cell infiltration of the adventitia were nondiagnostic but suggestive findings commonly observed. Ultrastructural alterations were most striking in the muscular media. Degenerating smooth muscle cells with elongated mitochondria, dilated rough endoplasmic reticulum, and autophagic vacuoles containing electron-dense material were observed. Macrophages and giant cells contained degenerated smooth muscle cell basement membrane within phagocytic vacuoles, and macrophages were found within smooth muscle. Although frequently found in the vicinity of macrophages and giant cells, disrupted elastic lamina was not demonstrated in phagocytic cells.

Axonal particles with electron-dense cores from arterial biopsy in polymyalgia arteritis.

Electron microscopic examination of nerve tissue from a patient with polymyalgia arteritis has shown the presence of electron-dense particles within the axons. These particles have a viral-like structure but lie within the size range of small neurosecretory vesicles and may represent alterations in these organelles. Myelin-like bodies have also been identified within non-myelinated axons and are suggestive of lysosomal end-products. These findings seem to bear out the proposition that the primary lesion in polymyalgia arteritis may be neurogenic in origin and offer some explanation of the pain experienced in the course of the disease.

Light and electron microscopic studies on human temporal arteries with special reference to alterations related to senescence, atherosclerosis and giant cell arteritis.

Temporal artery biopsy specimens from 26 patients of various ages with and without giant cell arteritis afforded an opportunity to examine several ultrastructural features of these human muscular arteries, including senescent and atherosclerotic alterations and the fine structural pathology of temporal arteritis. The unusual pathologic features of temporal arteritis were found superimposed on the progressive accumulation of smooth muscle cells, collagen and occasional discrete intimal atherosclerotic plaques in the intima of aging arteries. Two features of giant cell arteritis were conspicuous: first, the accumulation of large numbers of histiocytes and epitheloid and giant cells at the intimal-medial junction and second, fragmentation, degeneration and dissolution of the internal elastic lamina. The close proximity of the granulomatous reaction to the degenerating lamina suggests that these two aspects of the pathologic picture are in some way related, and possible immunologic mechanisms of this relationship are discussed on the basis of the ultrastructural findings.