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B Pakkenberg

Publications and source records attributed to B Pakkenberg.

At least 55 records · Page 3Linked to original sources

An efficient method for estimating the total number of neurons in rat brain cortex.

An efficient method for the unbiased estimation of the total number of neurons in rat brain cortex is presented. The method is reasonable fast, the counting procedure takes 2-3 h per rat, and gives an estimate of the total neuron number in cortex cerebri with an CE of 0.10. The rat cerebral cortex is found to have a mean volume of 253 mm3 and to contain a mean of 21 million neurons. The method has been used in a neurotoxicologic study, in which rats were given toluene perorally in doses of 200, 400 and 800 mg/kg/day, respectively, for 12 weeks, followed by an exposure-free period of 4 weeks. The total number of neurons in rat brain cortex cerebri showed no significant difference between exposed and non-exposed animals. The applicability of the method is discussed.

Animals↗

Optimizing sampling designs for volume measurements of components of human brain using a stereological method.

Measurements of the cerebral cortical volume used to be very laborious, due to the 3-D complexity of the gyral pattern. Using stereological methods, which allow the quantification of 3-D structures from measurements on 2-D cross-sections, the difficulties have been overcome. In thirty formalin-fixed normal human brains the total volumes were measured by saline displacement. The brains were serially sliced in coronal sections and the fractional areas of the cortex, white matter, central grey structures and ventricles were determined by point-counting. Using Cavaliéri's principle the volumes of these structures were calculated. The average cortical fixed volume was 549 ml (SD +/- 107) corresponding to 54% of the total volume of the hemispheres. The coefficient of error of the cortical volume determinations was 2.6%. The efficiency of the design and the possibilities for optimizing the design are discussed. This point-counting method was preferred to the use of an automatic image analyser, being precise, easy to handle and not interfering with further tissue processing for histological preparation.

Aged↗

New stereological method for obtaining unbiased and efficient estimates of total nerve cell number in human brain areas. Exemplified by the mediodorsal thalamic nucleus in schizophrenics.

Using a new stereological technique, the total number of nerve and glia cells can be estimated in selected brain regions. The method is completely independent of precise knowledge of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures. It therefore provides an unbiased estimate of total nerve cell number. As an example, the total neuron number from the mediodorsal nucleus of thalamus in brains from schizophrenic patients is compared to control cases. The total neuron number was reduced by 40% in the brains from chronic schizophrenic patients.

Adult↗

What happens in the leucotomised brain? A postmortem morphological study of brains from schizophrenic patients.

Volume measurements were carried out on 19 brains from leucotomised schizophrenic patients and 20 age- and sex-matched controls using a stereological method. The volume of the total fixed brain, hemispheres, cortex, white matter, and central grey matter were all significantly reduced compared with controls. White matter and central grey structures were significantly reduced compared with a group of non-leucotomised schizophrenic brains. No difference was found in the size of the lesions in patients who improved compared with the patients who remained unchanged and the outcome was unrelated to lesional asymmetry. Morphometric measurements were correlated to a number of clinical parameters.

Aged↗

The effect of MPTP on uridine uptake in murine nerve cells.

Sixty, 3-month-old, male Theiler mice were injected with 1 mg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) each i.p. Six groups of 5 animals each were then injected with 0.25 mCi [5-H3]uridine i.v. at intervals of 6h, 1,2,5,7 and 9 weeks after MPTP injection and each group was killed 1 h after uridine injection. Microautoradiograms were performed and the grain number determined in nerve cell nuclei in the striatum, substantia nigra and cerebral cortex. An initial increase in uridine uptake was found in substantia nigra, followed by a decrease during the following 9 weeks. A decrease in uptake occurred in the striatum from weeks 5-9, but without any initial increase. An increase in uptake was observed in the cortex 2 weeks after MPTP injection. Thus, in mice, a single injection of MPTP has a significantly prolonged effect upon the basic metabolic process (RNA synthesis) in substantia nigra and striatum. Selegiline, which causes a significant decrease in uridine uptake, also protects nerve cells from the effect of MPTP. The amount of dopamine in striatum and substantia nigra following MPTP did not change significantly during the 9 weeks. However, the amount of dihydroxyphenylalanine (DOPA) increased in both these areas during this period.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Total number of neurons and glial cells in human brain nuclei estimated by the disector and the fractionator.

Unbiased estimates of the total number of neurons and glial cells from central regions of grey matter in human brains are obtained using the disector principle in modifications which are unaffected by the histological processing of paraffin-embedded tissue. Section thickness does not enter into the estimator and need not be known. An analysis of the contributions from all sampling levels to the variance of the estimator of total cell number has been used to design an optimimal sampling scheme. Using this method, a precise and unbiased estimate of the total number of neurons in a defined brain region can be obtained in less than 1 h.

Brain↗

The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis.

The new stereological methods for correct and efficient sampling and sizing of cells and other particles are reviewed. There is a hierarchy of methods starting from the simplest where even the microscopic magnification may be unknown to the most complex where typically both section thickness and the magnification must be known. Optical sections in suitably modified microscopes can be used to improve the ease and speed with which even the most demanding of these methods are performed. The methods are illustrated by practical examples of applications to a wide range of histological entities including synapses, neurons and cancer cells, glomerular corpuscles and ovarian follicles.

Animals↗

Some new, simple and efficient stereological methods and their use in pathological research and diagnosis.

Stereology is a set of simple and efficient methods for quantitation of three-dimensional microscopic structures which is specifically tuned to provide reliable data from sections. Within the last few years, a number of new methods has been developed which are of special interest to pathologists. Methods for estimating the volume, surface area and length of any structure are described in this review. The principles on which stereology is based and the necessary sampling procedures are described and illustrated with examples. The necessary equipment, the measurements, and the calculations are invariably simple and easy.

Humans↗

Post-mortem study of chronic schizophrenic brains.

Volume measurements were carried out on 29 brains from institutionalised, chronic schizophrenic patients and 30 age and sex-matched controls using a stereological method. The volumes of the total fixated brain, the hemispheres, the cortex, and the central grey matter of the schizophrenic brains were significantly reduced while the volumes of the ventricles were significantly enlarged compared with the control group. The patients had been diagnosed by a psychiatrist on the basis of their case records as having either a Type I or Type II syndrome according to the symptoms they presented in the first years of their disease. The Type II patients were found to have significantly enlarged ventricles compared with the Type I patients.

Aged↗

The effect of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on uridine uptake in the mouse brain.

Male white mice were injected with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 40 mg/kg. After 2 h, 24 h, 2, 4 and 8 days 0.25 mCi [5-3H]uridine was injected i.v. and 1 h later the animals were sacrificed. In microautoradiograms the number of grains over the nerve cell nuclei was counted in the substantia nigra, the cerebral cortex, the hippocampus and the neostriatum. In the substantia nigra there was a significant increase in grain number after 2, 4 and 8 days. In a group of animals injected 3 days with MPTP and sacrificed 2 days after the last injection the same increase was found. In the other brain regions only an insignificant increase in grain counts was found. In a special group of animals the total radioactivity and distribution of label on metabolites in blood, brain and liver was determined. No significant changes were found.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Clozapine in the treatment of tremor.

In an open trial 25 tremor patients were treated with clozapine in small doses (18-75 mg per day). The effect was measured with a new movement analyzer. Nine of 12 essential tremor patients were greatly improved. In six of nine patients with Parkinson tremor and in two combined essential tremor/Parkinson tremor patients tremor almost disappeared. Sedation is a major side effect, but decreases in most patients with time. The risk of agranulocytosis makes blood control necessary.

Alcoholism↗

Clinical features and long-term treatment with pimozide in 65 patients with Gilles de la Tourette's syndrome.

During the last seven years 65 patients with Gilles de la Tourette's syndrome have been treated. Pimozide was used as the preferred drug because of our experience of treating other hyperkinesias which indicated fewer side-effects than with haloperidol. Of the 65 patients with Gilles de la Tourette's syndrome, 59 were treated with pimozide alone or in combination with tetrabenazine or clonidine. The dose ranges of pimozide were 0.5-9 mg per day. Eighty-one percent experienced a good clinical response without side-effects. The side-effects seen in our patients were sedation, gain in weight, depression, pseudoparkinsonism and akathisia; acute dystonic reactions, blurred vision, slurred speech and xerostomia did not occur. No cases of tardive dyskinesia were seen.

Adolescent↗

Effect of electrical convulsions on uridine labeling and activity pattern in nerve cells in mice.

Male white mice were exposed to electroshock and then injected intravenously with 5-[3H]uridine immediately after the shock. After 5, 30, or 60 min or 6, 12, or 24 h, the mice were killed, microautoradiographs were prepared, and grains were counted in the cortex, hippocampus, and basal ganglia. The results of the grain counts were compared with grain counts in the cortex, hippocampus, and basal ganglia of mice exposed to anoxia for 25 s and then treated in the same manner as the first groups. After electroshock the grain count decreased to 25% of that in control animals in the hippocampus and to 50% in the cortex but was normal in the basal ganglia. The counts returned to normal values within 6 h in the hippocampus, and within 1 h in the cortex. After anoxia, the grain counts were normal in the cortex and hippocampus but increased in the basal ganglia. The distribution of cells with a high or low grain count in vertical and horizontal columns of the cortex in control and convulsion animals was analyzed. There were random variations from column to column in both control and convulsion animals. In some anatomic layers there were significantly different grain counts, indicating differences in functional activity.

Animals↗

No global neocortical nerve cell loss in brains from patients with senile dementia of Alzheimer's type.

Precise estimates of total neuron numbers in neocortices of 11 women, mean age 82.6 years (range 79-88) with severe senile dementia of the Alzheimer's type (SDAT) were compared with similar estimates in 10 cognitively normal women of comparable mean age (84.1 years; range 74-92). The total mean nerve cell number in the SDAT group was 16.9 x 10(9) with a coefficient of variation (CV = SD/mean) = 0.14, whereas mean total neuron number in the control group was 18.1 x 10(9), CV = 0.18. In a material of this size the reduction of 6% in neocortical cell number in the SDATs is neither statistically nor biologically significant. Nevertheless, all patients with SDAT were severely demented, having a mean score of 5.6 on a 1-7-scale of dementia. This contrasts with the nondemented individuals who had lived an independent life at home until shortly before death. The SDAT patients showed a rather consistent reduction in cortical volume by 14%, an atrophy that was solely due to a reduced cortical thickness. In addition, all had multiple neocortical plaques (Bielschowsky silver stain).

Aged↗