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  • 1
    ISSN: 1432-0533
    Keywords: Brain ; Incomplete ischemia ; Acidosis ; Light microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Transient severe incomplete ischemia was induced in rats by a combination of bilateral carotid artery clamping and hypovolemic hypotension. Production of lactic acid in the ischemic brain was modified by preischemic administration of glucose or saline. After 30 min of ischemia and 5 or 90 min of recirculation, the animals were fixed by perfusion. High-resolution light microscopy based on whole hemisphere plastic sections revealed that the model produces a highly predictable ischemia in the telencephalon, with a more inconstant injury in the diencephalon, rostral brain stem, and cerebellum. The extent of injury correlates well with studies of local cerebral blood flow in the same model. The present study largely confirmed the opinion, based on the earlier study of the frontoparietal cortex, that the neuronal injury is predominantly of the ‘pale’ type, although fair amounts of ‘dark’ injury also appeared with predilection to the pyriform cortex, hippocampus, and occasionally the cerebellum. Excessive tissue lactic acidosis due to glucose pretreatment aggravated both types of neuronal injury. It was also accompanied by marked astrocytic edema as well as capillary obstruction in the group with long recirculation. A novel type of ischemic tissue change emerged, consisting of osmiophilic granules and whorls probably derived from damaged cell membranes.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 58 (1982), S. 87-94 
    ISSN: 1432-0533
    Keywords: Hypercapnia ; Rat brain ; Ultrastructure ; Cerebral edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is presently debated how much cellular acidosis contributes to brain cell damage during ischemia and hypoxia. To study the influence of acidosis occurring in the absence of energy failure, extreme hypercapnia was produced in anesthetized, artificially ventilated, and well oxygenated rats by increasing the inspired CO2 concentration until arterialPCO2 reached 150 or 300 mm Hg. At these CO2 tensions intracellular pH falls from a control value of about 7.05 to about 6.85 and 6.65, respectively. After 45 min the brains were fixed in perfusion and processed for light and electron microscopy. AtPaCO2 150 mm Hg no clear neuronal abnormality was detected, but atPaCO2 300 mm Hg some neuronal changes were observed. Notably, the nuclei showed slightly coarser chromatin than normally. In a few nerve cells mild swelling of mitochondria and dispersion of polysomes as well as detachment of ribosomes from the endoplasmic reticulum appeared. In both groups, slight to moderate astrocytic edema developed. Thus, even extreme hypercapnia, with its acompanying marked tissue acidosis, alters ultrastructure in the brain only to such a moderate extent that irreversible cell damage is unlikely. We conclude, therefore, that acidosis occurring during ischemia or hypoxia is detrimental only if pH is further lowered and/or if it occurs in conjunction with cerebral energy failure.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Brain ; Incomplete ischemia ; Acidosis ; Capillaries ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Excessive tissue lactic acidosis has earlier been shown to aggravate structural damage of both neurons and glial cells in the rat cerebral cortex. To study the reactions of cortical capillaries, light- and electronmicroscopic morphometry was used. Rats were subjected to severe incomplete ischemia (cerebral blood flow below 5% of normal) for 30 min by clamping their carotid arteries and by lowering the blood pressure. Lactate production during ischemia was modified by preischemic administration of either saline (low lactic acidosis group) or glucose (high lactic acidosis group). In the animals with low lactic acidosis, only minimal vascular changes were seen after both 5 min and 90 min recirculation. In the high lactic acidosis group, the endothelial cells were swollen after 5 min of recirculation, and the changes grew markedly worse during 90 min of recirculation. Nuclear chromatin coarsened and mitochondria swelled up. Morphometry showed that the lumen narrowed as a result of endothelial swelling. In spite of variable degree of perivascular astrocytic edema, the outer capillary diameter was little changed in the experimental groups. It seems likely that endothelial swelling hampers postischemic circulation in incomplete ischemia accompanied by high lactic acidosis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-6903
    Keywords: Alzheimer's disease ; cholinergic deficit ; CSF ; autopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cholinesterase (ChE) activity was measured as a possible marker of cholinergic neurotransmission of the brain in CSF of 93 patients with probable Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and of 29 control patients. ChE activity in CSF was decreased significantly in the AD/SDAT patients as compared to the controls. This reduction correlated significantly with the various measures of the severity of dementia. However, the reduction of ChE activity was only moderate (25–30%) even in patients with the most severe dementia and nonsignificant in patients with early symptoms of AD/SDAT. The significance of various confounding factors, which may interfere with CSF ChE measurements is discussed. Our findings seem to indicate that the deficiency of cholinergic neurons is not directly reflected in CSF and that the measurements of ChE activities in CSF are not helpful in diagnosing AD/SDAT. In the autopsy study the activities of cholineacetyltransferase (ChAT) and ChE were determined for ten brain areas of 20 AD/SDAT patients and of 14 controls. In AD/SDAT patients ChAT activity was profoundly decreased (50–85% decrease) in the cortical areas and hippocampus, but was unchanged or only mildly reduced in other subcortical brain areas. This study further confirms that the affection of cholinergic neurons is limited to projections from nucleus basalis to cortex and hippocampus, whereas other cholinergic neurons, like in striatum, seem to be relatively spared. In general, the activities of ChAT and ChE were lower in Alzheimer patients dying at younger age suggesting more severe disease process with these patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1463
    Keywords: Alzheimer's disease ; multi-infarct dementia ; combined dementia ; choline acetyltransferase ; post-mortem brain studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain choline acetyltransferase (ChAT) activity was determined in 43 patients with Alzheimer's disease (AD), 14 with multi-infarct dementia (MID), and 15 with combined dementia (CD) and in 53 age-matched controls. The activity of ChAT declined in the hippocampus, temporal and frontal cortex in patients with AD and CD compared to the controls. In the AD group the reduced activity of ChAT in all brain areas was associated with a greater number of cortical neurofibrillary tangles. The degree of dementia had a negative correlation with the activity of ChAT in the frontal cortex in both AD and CD patients. The activity of ChAT in the temporal cortex of CD patients was negatively associated with the cortical tangle counts. In contrast, the activity of ChAT and MID patients was not essentially different from that of the controls. Neither did the various clinical and neuropathological variables show any significant correlation with ChAT activity in MID patients. Thus, in this study the reduction in the activity of ChAT seems to be associated with Alzheimer-type pathology but not with dementia due to vascular changes.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 65 (1986), S. 51-62 
    ISSN: 1435-1463
    Keywords: Alzheimer's disease ; senile dementia ; multi-infarct dementia ; combined dementia ; dopamine receptors ; post-mortem brain studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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