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    Changes of retinal neurons and glial fibrillary acidic protein immunoreactive astrocytes in spontaneously hypertensive rats

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    OBJECTIVE: The influence of arterial hypertension on retinal neurons and glial fibrillary acid protein (GFAP) immunoreactive astrocytes was investigated in spontaneously hypertensive rats (SHRs). METHODS: The retinas of 4- and 6-month-old SHRs and age-matched Wistar-Kyoto rats (WKY) were investigated. A group of SHRs, treated from 4 to 6 months with the hypotensive drug hydralazine, was also examined. Microanatomical and immunohistochemical techniques associated with image analysis and the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) technique for apoptosis or necrosis were used, as well as astrocyte molecular biology (Western blot) techniques. RESULTS: In 4-month-old SHR and WKY rats, retinal morphology and the number of retinal neurons and of GFAP-immunoreactive astrocytes were similar, with the exception of the occurrence of 1% of TUNEL-positive ganglionic neurons in SHRs. In 6-month-old SHRs a decrease of retinal volume and of the number of ganglionic neurons and photoreceptors was observed, compared with age-matched normotensive WKY rats or younger SHR and WKY rats. Two per cent of ganglionic neurons and 5% of photoreceptors were also TUNEL positive. In 6-month-old SHRs, hypertrophic perivascular GFAP-immunoreactive astrocytes were found, whereas their number was unchanged compared to younger cohorts or WKY rats. An increased expression of GFAP was also noticeable in SHRs by Western blot analysis. Hypotensive treatment with hydralazine partly countered retinal changes occurring in SHRs

    Vascular and neuronal hypertensive brain damage: protective effect of treatment with nicardipine.

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    AIM: The brain is sensitive to hypertension, which causes a variety of vascular and neuronal cerebral changes. The present study was designed to assess the effect of long-term treatment with the Ca2+ channel blocker nicardipine on intracerebral (intraparenchymal) arteries in spontaneously hypertensive rats (SHR) by using microanatomical techniques associated with image analysis. The effects of hypertension and treatment with nicardipine on nerve cells and glial fibrillary acid protein (GFAP)-immunoreactive glial cells were also evaluated. EFFECTS OF NICARDIPINE ON BLOOD PRESSURE: In SHR a significant increase in systolic blood pressure in comparison with age-matched normotensive Wistar-Kyoto (WKY) rats was noticeable. Treatment with nicardipine significantly reduced systolic pressure in the SHR. The media: lumen ratio and the thickness of the tunica media were increased in medium (diameter between 150 and 50 microns and small (diameter < 50 microns intracerebral arteries. This phenomenon was accompanied by luminal narrowing. Treatment with nicardipine significantly reduced the thickness of the tunica media, the media: lumen ratio and increased the luminal area, primarily at the level of small pial arteries and of intracerebral arteries. EFFECTS OF NICARDIPINE IN THE BRAIN: In control SHR, the number of neurones in the frontal and occipital cortex was reduced in comparison with normotensive WKY rats. GFAP-immunoreactive astrocytes were increased in number (hyperplasia) and in size (hypertrophy), both in the frontal cortex and in the occipital cortex of control SHR. In the CA1, field of the hippocampus, the number of neurones and their size were decreased in SHR in comparison with normotensive WKY rats. Hyperplasia of GFAP-immunoreactive astrocytes of white matter and hypertrophy of those of grey matter was also noticeable. No important changes were found in other portions of the hippocampus. Treatment with nicardipine increased the number of neurones in the frontal cortex and in the occipital cortex of SHR and countered hyperplasia and hypertrophy of GFAP-immunoreactive astrocytes. Moreover, it increased the number of neurones in the CA1 field of the hippocampus and decreased the number and the size of astrocytes of the white matter and grey matter, respectively. CONCLUSIONS: These findings show that treatment of SHR with nicardipine significantly reduced systolic blood pressure and induced moderate vasodilation of both extracerebral and intracerebral arteries regulating cerebrovascular resistance. The compound also countered some microanatomical changes occurring in the hypertensive brain. The frontal and occipital (visual) cortex and the CA1 field of the hippocampus were the cerebral areas more sensitive to treatment with nicardipine. This suggests that nicardipine induces moderate cerebrovascular dilation and exerts neuroprotective effects on SHR neurones. The possible relevance of the neuroprotective actions of nicardipine in the hypertensive brain deserves to be evaluated in future studies

    Nicardipine and treatment of cerebrovascular diseases with particular reference to hypertension-related disorders.

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    Nicardipine is a second generation dihydropyridine-type Ca2+ antagonist with high vascular selectivity and strong cerebral and coronary vasodilatory activity. The compound is used in the treatment of hypertension, primarily in the elderly. In this review the main evidence of the cerebrovascular activity of nicardipine in preclinical studies using in vitro and in vivo models is detailed. A particular physico-chemical property of nicardipine is the almost complete protonation in acid environment. This allows its accumulation in ischemic brain regions and makes it a candidate for the treatment of cerebrovascular disorders characterised by impaired brain perfusion. The main clinical data on the use of nicardipine in cerebral ischemia and related disorders, subarachnoid haemorrhage and stroke, are also reviewed. These studies included 5940 patients affected by chronic cerebrovascular insufficiency (cerebral ischemia, cerebral atherosclerosis mainly associated with hypertension, transient ischemic attacks, sequelae of cerebral infarction, thrombosis or embolia, hypertensive encephalopathy), 1540 patients affected by sequelae of subarachnoid haemorrhage and 206 patients affected by stroke. Both preclinical studies and clinical trials have shown that nicardipine is a safe Ca2+ antagonist with powerful cerebrovascular activity. This suggests its possible use in cerebrovascular disorders in which blockade of Ca2+ channels of the L-type and/or selective cerebral vasodilatation is desirable. Further studies are necessary to establish if modulation of neuronal Ca2+ channels of the L-type by nicardipine may have a neuroprotective effect independent by the cerebrovascular activity of the compound

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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