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Biomedical subjects

W Meier-Ruge

Publications and source records attributed to W Meier-Ruge.

At least 19 recordsLinked to original sources

Age-related white matter atrophy in the human brain.

Aging of the brain involves not only appreciable shrinkage of the cortex and other gray matter structures but above all loss of white matter. This could be due to a decline in the number of myelinated fibers or to a loss of water. To assess the role played by each of these factors we studied brains from 33 neurologically intact subjects at autopsy representing three different age groups: 15-50, 51-70, and 71-93 years. The precentral gyrus, gyrus rectus, and corpus callosum were selected for investigation, with staining for alkaline phosphatase on native cryostat sections to visualize the capillary network, and staining for myelin on semithin sections for nerve fiber visualization. Atrophy was objectified by measuring the number of capillaries, the intercapillary distance, and capillary length, since the capillary network remains constant throughout normal life. A mean difference of 16-20% was found, representing white matter atrophy, between the oldest and youngest age-groups. The cortex of the corresponding gyri, on the other hand, showed a difference of less than 6%. Morphometric investigation of sections stained for myelin showed that the brains with a mean age of 78.7 +/- 6.6 years had 10-15% fewer myelinated fibers. This was only partly offset by an increase in the volume of extracellular space. Our findings show that the age-related decline in brain volume is much more a question of white matter atrophy than of brain cortex atrophy. White matter atrophy could be an indirect indicator of nerve cell loss, since the volume of a nerve cell is much smaller than its myelinated fiber.

Adolescent

Epidemiology of congenital innervation defects of the distal colon.

Congenital colorectal innervation defects were evaluated by studying 3699 colonic mucosal biopsy specimens obtained from 773 patients over a 5-year period (1986-1991). In 358 cases (46.3%) a classifiable defect was present, with aganglionosis in 187 of these patients (52.2%) and hypoganglionosis of the colon in 18 (5.0%). Hypoplastic or aplastic sympathetic innervation (type-A neuronal intestinal dysplasia was found in 2.2% (n = 8) and dysplasia of the parasympathetic submucous plexus (type-B neuronal intestinal dysplasia) in 40.6% (n = 145) of the patients with classifiable defects. Identification of a specific innervation defect was not possible in 229 of the 773 patients (29.6%), 28% of whom exhibited slight dysplasia and 30% immaturity or hypogenesis of the submucous plexus. In 40% of the unclassifiable cases heterotopic nerve cells were found in the muscularis mucosae and/or lamina propria mucosae, while 2% had severe heterotopia with the cells of the myenteric plexus completely displaced into the circular and/or longitudinal muscle layers. These patients generally suffered from severe chronic constipation requiring surgical intervention. Four congenital innervation defects of the colorectum can thus be clearly differentiated at present: aganglionosis (in its various forms), hypoganglionosis, type-A neuronal intestinal dysplasia, and type-B neuronal intestinal dysplasia.

Acetylcholinesterase

Microvascular morphometry in primate diaschisis.

Focal cerebral ischemia was produced in monkeys by transorbital occlusion of the right middle cerebral artery. Following this, in one group of animals the total microvasculature, including both perfused and nonperfused vessels of the opposite caudate nucleus and insula, was examined by alkaline phosphatase staining of the endothelium. In another group, the patency of the microvascular bed was visualized by india ink perfusion. The number, diameter, and length of visualized vessels were measured by means of a Wild ASBA image analysis system. The perfused patient microvascular bed was significantly reduced in both insula and caudate nucleus in the supposedly normal left side, although the total microvascular volume showed an increase at 4 and 12 hr in the insula and at 48 hr in the caudate nucleus. Reduced perfusion in the hemisphere opposite to the occluded middle cerebral artery provides an anatomical substrate for the phenomenon of "diaschisis."

Animals

Enlargement of synaptic size as a compensative reaction in aging and dementia.

A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions.

Aged

Histochemical and morphometric investigation of the pathogenesis of acute brain infarction in primates.

The right medial cerebral artery of 25 primates (Macaca radiata) was occluded transorbitally with an atraumatic clip. The time courses of infarct volume and capillary morphometric changes in the ischemic lenticular nucleus, caudate nucleus and insular cortex were then determined. Volume changes of ischemic foci were studied morphometrically using an enzyme histotopochemical acid phosphatase stain. During the first 4 hours extension (or spread) of the ischemic area was small and constant. Over the next hours, the ischemic focus increased in volume, becoming maximal in the lenticular nucleus in 24 hours and in the caudate nucleus in 48 hours. In the lenticular nucleus, edema developed 4 hours after onset of ischemia and was characterized by a decrease in capillary diameter and an increase in mean intercapillary distance. In the caudate nucleus and insular cortex, in the first hours after clipping the medial cerebral artery, capillary diameter and volume increased and intercapillary distance decreased. The data demonstrate that the therapeutic window of brain infarct treatment is during the first 4-6 hours after occlusion of the medial cerebral artery.

Acid Phosphatase

[Neuronal colon dysplasia in adulthood. Diagnosis, clinical aspects and therapy].

In patients with primary chronic constipation (n = 18) and diverticulosis of the sigmoid (n = 17) biopsies were examined enzyme-histochemically and the diagnosis of neuronal colonic dysplasia of the rectosigmoid was established. In eleven controls however a normal innervation was observed (p less than 0.001). Patients with neuronal colonic dysplasia usually failed to respond to conservative methods of treatment. Indication for surgery depended upon the duration and severity of the symptoms. The actual treatment--partial lateral submucous sphincterotomy, resection of the sigmoid colon or subtotal colectomy--was determined by the extent of the morphologically and functionally altered intestinal segment.

Adult

Diagnosis of neuronal colonic dysplasia in primary chronic constipation and sigmoid diverticulosis endoscopic biopsy and enzyme-histochemical examination.

Neuronal colonic dysplasia is a separate clinical entity belonging to the group of congenital defects of intestinal innervation. Its enzyme-histochemical diagnosis is possible by endoscopic biopsy examination of the rectosigmoid. Enzyme-histochemically, it is characterized by dysplasia of the submucous plexus secondary to developmental defects. The principal clinical feature is weak propulsive motility. A clinical study was carried out to investigate the role of neuronal colonic dysplasia in the aetiology and pathogenesis of primary chronic constipation and diverticulosis of the sigmoid colon in adults.

Acetylcholinesterase

Senile dementia: a threshold phenomenon of normal aging? A contribution to the functional reserve hypothesis of the brain.

Neurochemical investigations with normal aging brains show that in the first 70 years of life no major changes of the glycolytic pathway can be observed. Only in the following decades does a significant decrease of brain metabolic turnover occur. Changes in nerve cell size, one of the most relevant parameters in evaluating a diffuse nerve cell atrophy, appear in the brain cortex not earlier than between 85 and 94 years of age; a 21% nerve cell shrinkage is the mean. The results demonstrate that a significant decrease in turnover of the glycolytic pathway is followed by a significant but moderate shrinkage of the nerve cells after a delay of 10-15 years. Similar investigations in brains from senile demented subjects demonstrate that the change in glycolytic turnover is much more a quantitative than a qualitative phenomenon. In comparison with age-matched controls a decrease in glycolytic turnover of more than 60% is observed. Morphometric investigations of the nerve cell sizes in the brain cortex of senile demented subjects showed a decrease of 45-55% when compared with age-matched controls. When normal aging is compared with senile dementia it seems that old age dementia is a threshold phenomenon which starts if the glycolytic turnover drops below 50% of its value in young healthy adults. Physiological aging, however, stays within the range of the reserve capacity of normal brain performance. In conclusion, it seems that the exhaustion of the functional reserve capacity may shift an aging brain into a dementia syndrome.

Adult

[Classification of malformations of colorectal innervation].

Inborn errors of colorectal innervation can be classified in four different forms: 1. Aganglionosis (including total aganglionosis of the colon, Hirschsprung's disease, ultrashort Hirschsprung's segment and neurogenic sphincter achalasia) 2. Hypoganglionosis 3. Congenital malformation of sympathetic innervation of the colon (Neuronal Intestinal Dysplasia Typ A or NID A) 4. Congenital malformation of the submucous plexus (Neuronal Intestional Dysplasia Typ B or NID B). We find in 52.2% of our biopsies with a characteristic malformation of the colorectal innervation an aganglionosis. 40.6% are malformations of the submucous plexus (NID B). Half of the cases with Hirschsprung's disease are combined with NID B. 5.0% of the classified colorectal malformations of the innervation are a hypoganglionosis and 2.2% a NID A. An additional half of our biopsies cannot be introduced into the above given classification due to moderate malformations of the colorectal innervation (mild dysganglionosis, hypogenetic nerve cells of the submucous plexus, heterotopic nerve cells of the submucous and myenteric plexus).

Colon

Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease.

A computer-assisted morphometric study has been carried out on ethanol phosphotungstic acid (E-PTA) stained synaptic junctions in the human dentate gyrus supragranular layer from adult, old and Alzheimer's disease (AD)-affected patients. The number of synapses per unit volume of tissue (Nv = numerical density), the average area of the single junction (S) and the total area of the synaptic contact zones in a unit volume of tissue (Sv = surface density) were the 3 parameters taken into account. The synapse to neurone ratio was also calculated for each patient. During physiological aging, Nv and Sv significantly decreased and S increased, respectively. In the AD hippocampi, Nv and Sv underwent a further decrease which was in the range of more than 40% with reference to the adult values. S was the same as the old control group. In comparison with the adult values, the number of synapse/neurone decreased by 15.6 and 48% in old and AD patients, respectively. Nv, S and Sv, while reporting on discrete ultrastructural features of the synaptic junctional zones, are closely related to each other and, taken together per group of patients, may represent a reliable index of the morphological adaptive changes taking place at the synapses. Thus, the significant increase of S both in old and AD hippocampi may be regarded as a CNS plastic response to aging and disease, although the marked decrease of Nv and Sv supports that in AD synaptic ultrastructural alterations proceed beyond a critical threshold for functional recovery.

Aged

Senile plaques: staining for acetylcholinesterase and A4 protein: a comparative study in the hippocampus and entorhinal cortex.

In 20 unselected autopsy cases tissue blocks from the hippocampus with adjacent entorhinal cortex and neocortex were stained for acetylcholinesterase (AChE). From five brains shown to have large numbers of senile plaques tissue, adjacent to that taken for AChE tissue blocks, was embedded in paraffin and sections were immunostained for the A4 protein. The morphological aspects were compared. Equivalent types of plaques and plaque-like structures were observed in the A4- and ACHE-stained sections. On selected tissue blocks from patients with many senile plaques two immediately adjacent cryostat sections were stained, one for AChE and one for A4 protein. The same individual plaques could be identified on the two sections. These findings suggest that high AChE activity is intimately associated with the process of A4 protein formation and accumulation in plaques and that this association already occurs at a very early stage of plaque formation.

Acetylcholinesterase

The paradox of increased microvascular visualization with decreased perfusion in cerebral focal ischaemia in a primate model.

Microvasculature of the right caudate nucleus and insular cortex of monkeys with their right middle cerebral artery occluded was morphometrically measured with an image analysis system at 1/2, 4, 12, 24, and 48 hr and 2 weeks. A biphasic change in the microvasculature was observed. In the first phase up to 12 hr an increase in the number and length of the total microvasculature, visualized by alkaline phosphatase staining, along with a reduction in the number and length of the perfused part of the microvasculature, visualized by India ink perfusion, was observed. In the second phase after 48 hr, the number and length of the total microvascular bed as well as the perfused functional bed were significantly reduced.

Animals

Computer-assisted morphometry of synaptic plasticity during aging and dementia.

A computer assisted morphometric study has been carried out on synaptic membranes in the dentate gyrus supragranular layer and cerebellar glomerulus from adult, old and demented patients. Numerical (Nv) and surface (Sv) densities as well as average area (S) of the synaptic contact zones were calculated directly on electron microscopic negatives by means of an ASBA (Wild Leitz, AG) image analyzer properly programmed. The results showed a decrease of Nv in both the CNS areas investigated during aging and, to a higher extent, in senile dementia. S was found to be significantly increased in old and demented CNS as compared with adult values. In the old hippocampus Sv was decreased by 40% whereas no significant difference was present between old and adult cerebellum; in senile dementia this parameter underwent a significant decrease in both areas investigated. We interpret the present findings in terms of morphological remodelling capability of the synaptic junctional zones during aging and disease.

Aged

Fibronectin content of the annulus fibrosus in diabetic and non-diabetic sand rats.

Annulus fibrosus of intervertebral discs from diabetic and non-diabetic sand rats were examined by microspectrophotometry for fibronectin content. This was higher in the diabetic animals both in the dorsal and ventral parts and in the outer and inner lamellae of the annulus. It is suggested that diabetes-related changes in fibronectin are similar to changes in annular collagen observed in species other than sand rats.

Animals

Age-related changes in fibronectin in annulus fibrosus of the sand rat (Psammomys obesus).

Fibronectin stains were carried out and evaluated by microspectrophotometric techniques in annuli fibrosi of vertebral discs of sand rats (Psammomys obesus) of both sexes and two age groups, 13-18 months and over 2 years of age. The distribution of fibronectin in the annulus shows a centripetal gradient from the outer to the inner laminae. Fibronectin was significantly more abundant in the annuli of old than of young animals of corresponding sex. Sex differences were not significant. The dorsal segment contained more fibronectin than the ventral, but the difference was statistically significant only in the aged females. The outer laminae of the annuli appeared consistently higher in fibronectin content than the inner laminae.

Aging