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Biomedical subjects

B Pakkenberg

Publications and source records attributed to B Pakkenberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

The use of a stereological method to estimate the volume of Schistosoma mansoni granulomas: the effect of zinc deficiency.

A quantitative, stereological method to assess the volume of Schistosoma mansoni granulomas is presented and its use demonstrated in a study of zinc-deficient animals. Twenty-six mice were divided into two groups, and given zinc-deficient or control food. After 4 weeks, the mean weight gain and thymus size were lower in the mice on the zinc-deficient diet. Eight mice in each group were then each infected with 60 S. mansoni cercariae and these mice were killed 12 weeks post-infection. There were then more eggs in the livers of the zinc-deficient mice than in those of the infected controls (7400/female worm v. 3300/female worm; P = 0.02), probably because of impaired intestinal egg expulsion and impaired resorption of eggs in the deficient mice. The median proportion of each liver occupied by granulomas was 0.11 among the zinc-deficient mice and 0.09 among the pair-fed, control mice (P = 0.08), and the median liver volumes were 1400 and 1450 microliters (P = 0.49), respectively. The computed median volume of all the granulomas in each liver was 160 microliters in zinc-deficient and 132 microliters in control mice (P = 0.32), while median granuloma volume per egg was 8.6 and 8.7 nl (P = 0.93), respectively. In contrast to conventional methods, modern stereological methods can provide estimates of granuloma volume or granuloma volume fractions without any assumptions about the size, shape, orientation or distribution of the granulomas in the liver.

Animals↗
PubMed1997

Neocortical neuron number in humans: effect of sex and age.

Modern stereological methods provide precise and reliable estimates of the number of neurons in specific regions of the brain. We decided to estimate the total number of neocortical neurons in the normal human brain and to analyze it with respect to the major macro- and microscopical structural components, to study the internal relationships of these components, and to quantitate the influence of important physiological variables on brain structure. The 94 brains reported represent a consecutive collection of brains from the general Danish population. The average numbers of neocortical neurons were 19 billion in female brains and 23 billion in male brains, a 16% difference. In our study, which covered the age range from 20 years to 90 years, approximately 10% of all neocortical neurons are lost over the life span in both sexes. Sex and age were the main determinants of the total number of neurons in the human neocortex, whereas body size, per se, had no influence on neuron number. Some of the data presented have been analyzed by using new mathematical designs. An equation predicting the total neocortical neuron number in any individual in which sex and age are known is provided.

Adult↗
PubMed1997

Total number and size distribution of motor neurons in the spinal cord of normal and EMC-virus infected mice--a stereological study.

The encephalomyocarditis virus of the diabetogenic M-strain (EMC-M) is known to cause diabetes in mice. The EMC-M virus has also been shown to cause paresis in some of the infected animals. The clinical features include an acute ascending predominantly motor paralysis, developing within days. This resembles acute idiopathic polyneuritis. The alpha motor neurons would be a possible target for the virus, so two parameters, the total number and the size distribution of motor neurons, were therefore selected for further investigation in 6 mice with neurological involvement and compared with 6 control mice. The optical fractionator method was applied for estimating the total number of motor neurons and the 3D size distribution was estimated using the rotator method in a vertical design. No difference was found in the total number of motor neurons and the size distributions were similar in the 2 groups. This design can be used as a model for the estimation of the total number of motor neurons and their size distribution in other experimental animal models.

Animals↗
PubMed1996

Muscarinic, N-methyl-D-aspartate (NMDA) and benzodiazepine receptor binding sites in cortical membranes from amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder causing marked pathology in the motoneuron system. The pathophysiology of the selective degeneration of motor neurons in the disease is as yet unknown, but evidence suggests that excitotoxic mechanisms might be involved. The present study was undertaken to determine whether defects in neurotransmitter receptors are involved in the disease, analyzing uniformly sampled specimens from neocortex and motorcortex. The binding to benzodiazepine, muscarinic cholinergic, and NMDA receptors in ALS brains was compared to that in control brains, using a single radioligand concentration of [3H]Ro 15-1788, [3H]QNB and [3H]MK-801. The benzodiazepine and the muscarinic cholinergic receptor binding was unaffected in any cortical region from the ALS subjects compared to controls. NMDA receptor binding labeled by [3H]MK-801 was significantly increased in several neocortical regions in the ALS group compared to the control group. Scatchard analysis of [3H]MK-801 binding in frontal cortex revealed a single binding site with an unaltered maximal binding capacity but an increased binding affinity of the site in the ALS group compared to the controls. The generalized alteration in the affinity of the binding site for [3H]MK-801 in the ALS cortex may indicate a modification of the NMDA receptor due to different sensitivity for endogenous modulators or to a different subunit composition of the NMDA receptor in ALS with altered functional properties. These findings may reflect a pathophysiological phenomenon in ALS.

Aged↗
PubMed1995

A stereological study of substantia nigra in young and old rhesus monkeys.

The number of pigmented and non-pigmented neurons in the substantia nigra (SN) of 10 old and six young female Macaca mulatta monkeys and in three old alpha male monkeys were estimated using new stereological cell counting methods. No systematic right-left differences were noted, nor were old animals different from young ones with respect to SN volume (68.9 mm3 vs. 62.8 mm3) or absolute number of nerve cells (320,000 vs. 312,000). However, the total number of pigmented neurons was about eight times higher in old animals compared with young ones (166,000 vs. 21,400) while the total number of non-pigmented SN neurons was less than half in old animals compared with young ones (139,000 vs. 285,000). These differences create difficulties in generalizing experimental results from the rhesus animal model to man. It seems unlikely that a simple correlation can be made between pigmented and tyrosine hydroxylase (TH) positive neurons in SN in monkeys. Instead of estimating the total number of pigmented and non-pigmented cells, only SN neurons positive for TH using immunohistochemical techniques might be used an indicator of the total number of dopaminergic neurons in SN in monkeys.

Age Factors↗
PubMed1995

Solutions to old problems in the quantitation of the central nervous system.

New stereological techniques, superior to conventional methods in quantitating macroscopic and microscopic structures in the central nervous system, have been developed within the last decade. By the use of a new counting method, the dissector, it is possible to obtain an efficient and yet precise estimate of the total number of neurons in any specific region, where a delineation of the region can be made, and the cells identified. The method has been applied to brains from patients with different neurological disorders. The latest effort has concentrated on the estimation of the total neocortical neuron number in brains from normal individuals of both sexes in the age from 20 to 90 years to see whether there are differences in total neocortical neuron numbers between males and females.

Adult↗
PubMed1994

Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals.

Significant loss of noradrenergic neurons of the locus coeruleus in aging and Alzheimer's disease has been reported. The interpretation of these analyses, however, is problematic because of the model- and assumption-based nature of conventional sampling and estimation techniques. In the present study, unbiased stereological methods were used to estimate the total number and mean cell volume of pigmented neurons of the locus coeruleus in the brains of young and aged nondemented persons. No side-to-side differences are seen, and there is no change in pigmented cell number or size in the locus coeruleus of nondemented older persons as compared with that of young individuals. In light of previous studies that show severe locus coeruleus cell loss in Alzheimer's disease, these data support further critical investigations into the possible protective role of noradrenaline in normal cognitive functions and emphasize the importance of avoiding methodological bias in quantitative neuroanatomical studies.

Adult↗
PubMed1993

Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical disectors.

The total number of neurons was estimated in eight brains from chronic schizophrenic men and compared with 16 gender- and age-matched controls. The average total neocortical nerve cell number was 22.12.10(9) in schizophrenics and 22.06.10(9) in controls. The estimate of total cell numbers can not demonstrate more subtle neuronal losses of specific cell types or cell loss in specific regions, but the result does not indicate that a major cell loss in the neocortex of schizophrenics is part of the disease. The sampling scheme was based on a uniform sampling design, the counting was performed using new stereological principles and the majority of the cerebral cortex was left intact providing the possibility for resampling and further analysis.

Adult↗
PubMed1993

Do alcoholics drink their neurons away?

Although it is commonly believed that chronic alcohol abuse results in loss of neocortical neurons, this assumption has not been properly tested. We used new stereological techniques to make a precise and unbiased estimate of the total number of neurons in the neocortex of brains obtained at necropsy from 11 chronic alcoholic men and 11 control men. The groups were matched with respect to age and height. Total mean neocortical neuron numbers in the two groups did not differ (alcoholics 23.4 x 10(9), controls 23.2 x 10(9)). Estimation of macroscopic brain volumes showed significant reductions in alcoholics compared with controls of the volume/weight ratios of white matter (11%, p = 0.013) and of archicortex (30%, p = 0.028). The volume of the ventricles in the alcoholic group was enlarged by 26%, but this was not statistically significant. There was no difference in the volumes of the neocortices. Our study confirms that chronic alcoholics lose white matter, and this could provide the basis for their functional impairment. However, the results also suggest that the observed brain damage in the alcoholic group is potentially reversible since preserved nerve-cell bodies might allow lost or malfunctioning axons to re-established and restored to function after prolonged abstinence and/or treatment. By contrast, lost neocortical neurons cannot be replaced.

Alcoholism↗
PubMed1993

Cerebral atrophy in AIDS: a stereological study.

Stereological estimates of mean volumes, surface areas, and cortical thicknesses were obtained on formalin-fixed brains from 19 men with AIDS and 19 controls. Volumes of neocortex, white matter, central brain nuclei, ventricles and archicortex were estimated using point counting and Cavalieri's unbiased principle for volume estimation. In AIDS, the mean volume of neocortex was reduced by 11%, and that of the central brain nuclei by 18%. Mean ventricular volume was increased by 55%. Mean neocortical thickness was reduced by 12%. The mean volume of white matter was reduced by 13%. The findings in 6 clinically demented AIDS patients were not statistically different from the rest of the group.

AIDS Dementia Complex↗
PubMed1993

Leucotomized schizophrenics lose neurons in the mediodorsal thalamic nucleus.

It has previously been shown that chronic schizophrenic patients have a 40-50% reduction in the total number of nerve and glia cells in the mediodorsal thalamic nucleus and the nucleus accumbens compared with controls, while the total neuron and glia number is the same in the two groups in the ventral pallidum. Using new stereological cell counting methods, neuron and glia cell numbers were estimated in the mediodorsal thalamic nucleus, the ventro-medial part of nucleus accumbens and the ventral pallidum in nine brains from leucotomized schizophrenics. This number was compared with counts from control cases and chronic schizophrenics without leucotomy. The results showed that the total number of nerve cells in the mediodorsal thalamic nucleus was statistically significantly reduced from 1.08 x 10(6) in chronic schizophrenics to 0.88 x 10(6) in leucotomized schizophrenics. Total neuron number was statistically significantly reduced in the ventro-medial part of the nucleus accumbens in schizophrenics without further reduction in leucotomized schizophrenics. The total neuron number in ventral pallidum was normal. With frontal leucotomy it is possible to investigate the consequences of disconnection of the prefrontal cortex to central regions in the human brain. The mediodorsal nucleus of thalamus represents a major efferent projection to the prefrontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A quantitative study of the human cerebellum with unbiased stereological techniques.

Estimates of total number of different neuron and glial cell types in the dentate nuclei and the four major regions of the human cerebellum were obtained by new stereological methods. With the optical disector and Cavalieri methods, the total number of neurons and glial cells in the human cerebellum of five elderly men was estimated to be 105,000 x 10(6) (coefficient of variation, CV = 0.13). Of this total, the granule cells comprised 101,000 x 10(6) (CV = 0.13) and the Purkinje cells comprised 30.5 x 10(6) (CV = 0.13) of the neurons. The mean of the total number of neurons in the dentate nucleus was 5.01 x 10(6) (CV = 0.28). The average surface area of the human cerebellum was estimated to be 1160 cm2 (CV = 0.29). The rationale for the different sampling schemes used to quantify the various cell types is described.

Cell Count↗
PubMed1992

The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics.

Reductions of 40% in total cell number and 25% in volume of the mediodorsal thalamic nucleus were recently reported in an unbiased neurostereological study of neuroleptic-treated schizophrenic patients. In order to investigate whether these results might be secondary to many years of treatment with neuroleptic drugs, eight brains from schizophrenics never treated with neuroleptics and eight controls were studied using the unbiased Cavalieri volume estimator. To compare left-right differences in this region, twelve neuroleptic-treated schizophrenics and eleven control cases were compared. The brains used for the left-right comparison study and five of 20 used for comparison of treated and untreated brain volumes have been used in an earlier study. The mediodorsal thalamus volume was reduced by 31% in untreated schizophrenics and by 22% in neuroleptic-treated schizophrenics. No differences were found in mean total volume of the left and right mediodorsal thalamus in brains from controls nor from schizophrenics. A major difference exists with respect to time of fixation in controls (12 years) and untreated schizophrenics (39 years) that makes shrinkage differences a possible confounding variable. The results suggest that the consistent reduction in number of neurons in the mediodorsal thalamic nucleus are not secondary to prolonged treatment with neuroleptic drugs and that asymmetry in this specific brain region is not a feature of the schizophrenia-afflicted brain.

Adult↗
PubMed1992

Stereological quantitation of human brains from normal and schizophrenic individuals.

The complex organization and high density of nerve cells in the human brain presents a challenge to the estimation of total cell numbers. The first unbiased counting method, the disector, was described in 1984 and has since made it possible to accurately count total neuron numbers in any region that can be defined, while excluding artifacts of earlier counting methods. The disector method has been applied to normal neocortex and to four subcortical brain regions from schizophrenics and controls. The total neuron number in neocortex in 26 normal individuals was estimated to be 25.10(9). A 40 and 50% reduction of total nerve cell number was found in the mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics, respectively. Furthermore, the Cavalieri principle has been used to estimate the volume of human cortex, white matter, central grey regions and the volume of the ventricular system in both controls and schizophrenics. As shown by these studies, the introduction of unbiased stereological methods and subsequent modifications in recent years have made it possible to estimate a number of parameters in the human brain without the biases included in most classical works. By comparison, earlier conventional counting methods have been relatively time consuming, mostly biased to a smaller or larger degree, and generally less precise. The application of these new neurostereological methods will undoubtedly provide greater confidence for future brain studies.

Adult↗
PubMed1991

The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method.

Using an unbiased stereological technique, the total numbers of pigmented and non-pigmented neurons were estimated in the substantia nigra of seven patients with Parkinson's disease and seven control patients. Compared with the controls, in which the average total number of pigmented neurons was 550,000, the number of neurons was reduced by 66% in the patients. The average total number of non-pigmented neurons was 260,000 in controls and reduced by 24% in the patients. A significant correlation (r = 0.81) existed between the total numbers of pigmented and non-pigmented neurons in the controls, whereas a similar correlation (r = 0.72) in the patients fell just short of statistical significance. The stereological estimates made in this study are unbiased, in that they are independent of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures. The stereological method is considerably more efficient than previous conventional methods.

Aged↗
PubMed1990

Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics.

Using a new and unbiased stereological technique, the total numbers of neuron and glial cells in the mediodorsal thalamic nucleus and the nucleus accumbens were found to be significantly reduced in schizophrenic patients compared with controls. The total neuron and glial cell number in the ventral pallidum and in the basolateral nucleus of amygdala did not differ in the two groups.

Adult↗