The microvascular changes in cases of hereditary multi-infarct disease of the brain.
ABSTRACT A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.
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ABSTRACT: The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, and superoxide production in kidneys of aged rats and whether these changes are exacerbated in aged rats with cognitive impairment. Twenty aged rats (male, 27 months) were divided into an Old Impaired group (n=9) and an Old Intact group (n=11) according to a cognitive function test. A group of 12-month-old rats (n=10) was used as a Young Intact group. Serum creatinine was increased significantly in the Old Impaired group, suggesting impaired renal function. Aged rats showed glomerulosclerosis and tubulointerstitialfibrosis. These pathological changes were markedly aggravated in the old cognitively impaired than in the old cognitively intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of IL-6, Nox2, ETa receptors and superoxide production were increased whereas mitochondrial SOD (MnSOD) and ETb receptors expression were decreased in kidneys of the aged rats. Interestingly, these changes were more pronounced in the old impaired than in the old intact rats. In conclusion, the aging-related kidney damage was exacerbated in aged rats with cognitive impairment. Klotho, ETB, and MnSOD were downregulated but ETa, IL-6, Nox2, and superoxide production were upregulated in the aging-related kidney damage. These changes were more pronounced in rats with cognitive impairment.Age 09/2011; 33(3):261-74. DOI:10.1007/s11357-010-9176-2 · 3.45 Impact Factor
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ABSTRACT: To evaluate visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Three subjects (one male and two females, mean age 55.3+/-2.9 years) belonging to an Italian family already diagnosed with CADASIL through clinicopathological and genetic studies and 14 control subjects (6 males and 8 females, mean age 52.7+/-3.6 years) were enrolled in the study. Flash electroretinogram (ERG), oscillatory potentials (OPs) and simultaneous recordings of pattern electroretinogram (PERG) and visual evoked potentials (VEPs) were assessed in all 3 subjects with CADASIL and age-matched controls. Subjects with CADASIL showed: reduced ERG, OP and PERG (N35-P50, P50-N95) amplitudes with respect to our normal limits; delayed PERG (N35, P50) and VEP (P100) implicit times when compared with our normal limits; and VEP (N75-P100) amplitudes and retinocortical times within our normal limits. Subjects with CADASIL present a dysfunction in the outer, middle and innermost retinal layers when the index of neural conduction in the postretinal visual pathways is normal. The delay in visual cortical responses observed in subjects with CADASIL may be ascribable to retinal impairment with a possible functional sparing of the postretinal visual structures.Clinical Neurophysiology 10/2000; 111(9):1582-8. DOI:10.1016/S1388-2457(00)00366-7 · 2.98 Impact Factor
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ABSTRACT: Tourette's syndrome (TS) is a disorder characterized by simple and complex motor tics, vocal tics, and frequently obsessive-compulsive symptoms. Its onset occurs before the age of 21. Typically, TS shows a waxing and waning course, but a chronification of the tics, even during later life, is often observed. TS mainly occurs in boys, and shows genetic heritability with differing penetrance. The pathological mechanism is still unclear Neuroanatomical and neuroimaging studies, as well as effective treatment using antipsychotics, suggest that a disturbance of the dopaminergic system in the basal ganglia plays an important role in the pathogenesis of TS. Several possibly causative mechanisms of the disturbed dopaminergic neurotransmission are discussed, with the main emphasis on the-infection-triggered-inflammatory immune process. Extrapyramidal movement disorders are known to occur as a symptom of poststreptococcal disease, such as in Sydenham's chorea. Cases of childhood TS are proposed to be caused by such a poststreptococcal mechanism, being part of a spectrum of childhood neurobehavioral disorders termed pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). The overlap between TS and PANDAS is discussed, and a critical view of the PANDAS concept is presented. The therapeutic implications of the different pathological mechanisms are described, taking into consideration not only the acute or chronic natures of different infections, but also an autoimmune process. Moreover, therapeutic strategies using typical and atypical antipsychotics, and also experimental therapies such as repetitive transcranial magnetic stimulation and deep brain stimulation, are critically discussed.Dialogues in clinical neuroscience 02/2007; 9(2):161-71.