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H Heinsen

Publications and source records attributed to H Heinsen.

At least 19 recordsLinked to original sources
PubMed2000

Cerebellar vermis area in schizophrenic patients - a post-mortem study.

Neuroimaging studies of cerebellar atrophy in schizophrenia have yielded contradictory results. In computer-tomography (CT) studies, cerebellar atrophy was found in up to 40% of schizophrenic patients. However, several recent magnetic resonance imaging (MRI) studies could not replicate these early findings; in addition, contradictory observations of enlargement of vermal structures were reported. In contrast to the number of CT and MRI studies, there are only a few neuropathological reports on this subject. In a post-mortem study we analyzed the midsagittal vermal area of formaldehyde-fixed cerebella of 12 deceased schizophrenic patients and 12 age- and gender-matched control subjects by using morphometrical methods. Statistical analysis using ANOVA revealed no significant group effects, but there were interactions with gender and cerebellar brain weight. In view of the present results, the common concept of cerebellar atrophy in schizophrenic patients appears premature. Gender effects and secondary processes (e.g., relevant alcohol or drug abuse) cannot be excluded as possible factors causing decrease of vermal areas in schizophrenic patients.

Adolescent↗
PubMed2000

Celloidin mounting (embedding without infiltration) - a new, simple and reliable method for producing serial sections of high thickness through complete human brains and its application to stereological and immunohistochemical investigations.

Celloidin mounting (embedding without infiltration) of the human central nervous system (CNS) proved to be superior to gelatin embedding for the production of serial sections ranging in thickness from 220 to 500 microm. After gallocyanin-staining, a comprehensive neuroanatomical as well as neuropathological survey of the human brain is possible, including diagnosis of Alzheimer's disease. Details of a fractionator analysis of the total striatal neuron number are described and the possible quantitative analysis of parallel immunohistochemically stained sections is discussed.

Adult↗
PubMed2000

Use of cryostat sections from snap-frozen nervous tissue for combining stereological estimates with histological, cellular, or molecular analyses on adjacent sections.

Adequate tissue preparation is essential for both modern stereological and immunohistochemical investigations. However, combining these methodologies in a single study presents a number of obstacles pertaining to optimal histological preparation. Tissue shrinkage and loss of nuclei/nucleoli from the unprotected section surfaces of unembedded tissue used for immunohistochemistry may be problematic with regard to adequate stereological design. In this study, frozen cryostat sections from hippocampal and cerebellar regions of two rat strains and cerebellar and cerebral regions from a human brain were analyzed to determine the potential impact of these factors on estimates of neuron number obtained using the optical disector. Neuronal nuclei and nucleoli were clearly present in thin sections of snap-frozen rat (3 microm) and human (6 microm) tissue, indicating that neuronal nuclei/nucleoli are not unavoidably lost from unprotected section surfaces of unembedded tissue. In order to quantify the potential impact of any nuclear loss, optical fractionator estimates of rat hippocampal pyramidal cells in areas CA1-3 and cerebellar granule and Purkinje cells were made using minimal (1 microm) upper guard zones. Estimates did not differ from data reported previously in the literature. This data indicates that cryostat sections of snap-frozen nervous tissue may successfully be used for estimating total neuronal numbers using optical disectors.

Animals↗
PubMed1999

Nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease.

We estimated the total neurone number, glial number, and glial index (ratio glial cells/neurone) in the thalamic mediodorsal nucleus (MD) in seven patients suffering from Huntington's disease (HD; four males, three females, mean age 52.4 +/- 13.6 years) and age- and sex-matched controls (four males, three females, mean age 53.6 +/- 12.1 years) by means of a stereological protocol. The mean total neurone number (N(T)) in the MD of controls was 2,985,188 +/- 174,710, the mean glial number (G(T); astrocytes, oligodendrocytes) 21,785,008 +/- 2,986,678, and the glial index 7.29 +/- 0.88. In HD, the average neurone number was decreased by 23.8% to 2,275,321 +/- 247,162 (Mann-Whitney U-test P < 0.05), the mean glial number by 29.7% to 15,318,895 +/- 1,722,524 (Mann-Whitney U-test P < 0.05), the glial index was slightly reduced to 6.81 +/- 1.06. Gallyas' impregnation for the demonstration of fibrous astroglia gave strongly positive results in all cases with HD and negative results in the controls. The morpho-functional correlation of the results is complicated because individual variability, presence of segregated and parallel neuronal circuits, and plasticity of the adult human CNS must be considered.

Adult↗
PubMed1999

Nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease. II. Optimization of a stereological estimation procedure.

This study provides the theoretical background of the decision to count approximately 750-1,300 neurons per individual in the preceding study of Heinsen et al. [6] finding a significant (P < 0.05) nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease with the so-called V(Ref) x N(V) method. Using a computer simulation of the study of Heinsen et al., it was shown that the legitimation for counting only 100-200 neurons per individual in previous studies comparable to that carried out by Heinsen et al. was based on incorrect assumptions. In this context it was of particular importance to confirm the theoretical prediction in the literature that the random error of total neuron number estimates obtained with the V(Ref) x N(V) method is actually greater than assumed in current stereological studies. In summary, this study revives the question of how many individuals need to be investigated and how many neurons (or other cell types, respectively) need to be counted per individual in studies comparable to that carried out by Heinsen et al.

Adult↗
PubMed1996

Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington's disease.

The centromedian-parafascicular complex represents a nodal point in the neuronal loop comprising striatum--globulus pallidus--thalamus--striatum. Striatal neurone degeneration is a hallmark in Huntington's disease and we were interested in estimating total neurone and glial number in this thalamic nuclear complex. Serial 500-microns-thick gallocyanin-stained frontal sections of the left hemisphere from six cases of Huntington's disease patients (three females, three males) and six age- and sex-matched controls were investigated applying Cavalieri's principle and the optical disector. Mean neurone number in the controls was 646,952 +/- 129,668 cells versus 291,763 +/- 60,122 in Huntington's disease patients (Mann-Whitney U-test, P < 0.001). Total glial cell number (astrocytes, oligodendrocytes, microglia, and unclassifiable glial profiles) was higher in controls with 9,544,191 +/- 3,028,944 versus 6,961,989 +/- 2,241,543 in Huntington's disease patients (Mann-Whitney U-test, P < 0.021). Considerable increase of fibrous astroglia within the centromedian-parafascicular complex could be observed after Gallyas' impregnation. Most probably this cell type enhanced the numerical ratio between glial number and neurone number (glial index: Huntington's disease patients = 24.4 +/- 8.1; controls = 15.0 +/- 5.2; Mann-Whitney U-test, P < 0.013). The neurone number in the centromedian-parafascicular complex correlated negatively, although statistically not significantly, with the striatal neurone number. This lack of correlation between an 80% neuronal loss in the striatum and a 55% neurone loss in the centromedian-parafascicular complex points to viable neuronal circuits connecting the centromedian-parafascicular complex with cortical and subcortical regions that are less affected in Huntington's disease.

Adult↗
PubMed1996

Variability in the human entorhinal region may confound neuropsychiatric diagnoses.

The human entorhinal region consists of a number of areas; however, there is no generally accepted nomenclature for these cytoarchitectonic fields, and the designation of its constituent layers or strata is a matter of controversy. Here, we consider a hitherto neglected adjacent field, the preamygdaloid claustrocortex. Its medial subfield has a small common border with the rostromedial entorhinal region (width maximal 2 mm). Both fields are cytoarchitectonically rather similar. The rostromedial oral entorhinal field lacks ascending terminal islands. Its unusually small pre-alpha cells are arranged in a thin band or small clusters consisting of pyramidal, triangular, or polymorphic cells. The conspicuous chromophilic pre-beta cell clusters are composed of a variety of cell types, including groups of 'immature' spindle-shaped or bipolar nerve cells. Furthermore, a rare sulcus within the entorhinal region (central sulcus of the entorhinal region: observed in 4% of the 450 brains examined) is associated with an unusual lamination of the entorhinal layers in its wall and floor. Both the specific shape and arrangement of neurones in the claustrocortical-rostral entorhinal border region and the unusual lamination within the rare central entorhinal sulcus are regarded as reflecting neurodevelopmental disturbances characteristic of schizophrenic brains. In contrast, our observations in a large sample of serially sectioned brains from controls, schizophrenics, and patients suffering from neuropsychiatric diseases other than schizophrenia do not support this assumption.

Adult↗
PubMed1996

Cytoarchitectonics of the human nucleus accumbens.

More than 400 publications per year deal with the Nucleus accumbens, however its morphological substrate and anatomical borders appear arbitrary. With a modified Nissi-technique applied to complete sets of thick serial, frontoparallel sections, it became possible to characterize the human Nucleus accumbens. In two series a clear delineation of its borders is documented. Along its rostro-caudal axis, the Nucleus accumbens shows morphological differences: the rostral Nucleus accumbens exhibits a higher cell-density and basophilia than Nucleus caudatus and Putamen; in caudal planes, the Nucleus accumbens dissolves into cell-clusters. A hitherto unrecognized supracommissural part of the Nucleus accumbens dorsal to the Commissura anterior is contiguous to the medial and lateral parts of the Nucleus interstitialis striae terminalis. The thickness of the hemispheric slices (approximately 600 micrometers) facilitated the topographical unravelling of the surrounding cell-islands. In accordance with Sanides (1957) these islands were referred to as Insulae terminales. Based on their topography and cellular structure, they were termed insulae terminales subputaminales (ltsp), Insulae terminales nuclei accumbentis (Itna), Insulae terminales supracommissurales (Itsc) and Insulae terminales olfactoriae mediales et laterales (Itom, Itol). The Insulae terminales form an almost complete envelope around the human Nucleus accumbens and could correspond to the neurochemically defined accumbal shell-region of the rat. Marked differences between medial and lateral insulae terminales olfactoriae permit a clear delineation between the human Nucleus accumbens and the lateral, rudimentary Tuberculum olfactorium: the basis for modifying the concept of a ventral striatum in man.

Adult↗
PubMed1995

Regional differences in the interaction of the excitotoxins domoate and L-beta-oxalyl-amino-alanine with [3H]kainate binding sites in human hippocampus.

The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus.

Aged↗
PubMed1995

Unsuspected (clinically silent) multiple sclerosis. Quantitative investigations in one autoptic case.

The incidental retrieval of a few, well-circumscribed, chronic multiple sclerosis plaques in a 49-year-old female who died from myocardial infarct is reported. In serial gallocyanin stained frontal sections of the brain one plaque in the left and four plaques in the right hemisphere were encountered. A total of 1.25 cm3 or 0.24% of the right hemispheric volume and a total of 0.93 cm3 or 0.2% of the left hemispheric volume was afflicted. The size as well as the topography of the plaques could explain the absence of clinical symptoms. Methodological issues concerning in vivo and post mortem diagnosis of multiple sclerosis and their impact on the epidemiology of this disease are discussed.

Astrocytes↗
PubMed1994

Neurofibrillary tangles without cell loss in the lateral vestibular nucleus of patients with Alzheimer's disease.

The lateral vestibular nucleus (LVN, nucleus of Deiters) was examined in the brains of four control subjects and four patients with dementia of the Alzheimer type (DAT). Neuronal counts on sections stained with silver and a polyclonal antibody to human choline acetyltransferase (ChAT) revealed an undiminished number of LVN neurons in patients with DAT. Numerous silver-stained neurofibrillary tangles (NFTs) were found in the DAT group, some also in the LVN of controls. These findings suggest that DAT affects LVN neurons, however without causing neuronal loss.

Aged↗
PubMed1994

Memantine inhibits [3H]MK-801 binding to human hippocampal NMDA receptors.

The antispastic agent and N-methyl-D-aspartate (NMDA) receptor antagonist memantine has recently been proposed as a neuroprotective drug for use in patients with dementia syndromes with primarily temporal lobe pathology, e.g. senile dementia of Alzheimer type or dementia in Parkinson's disease. In a quantitative autoradiographic study in human post mortem hippocampus, memantine was able to inhibit binding of the noncompetitive NMDA-antagonist [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) with inhibition constants between 3 and 10 microM, being about a factor of 10 more potent than the dissociative anaesthetic and NMDA receptor antagonist (+/-)ketamine. As these inhibition constants are well within the therapeutic concentration range of memantine, antagonism of endogenous glutamate at limbic NMDA receptors may be one molecular mechanism by which memantine is beneficial in dementia syndromes.

Aged↗
PubMed1994

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) inhibit [3H] alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) binding in human hippocampus.

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) have been investigated with regard to their potency to inhibit [3H] alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA) binding in human hippocampus in a quantitative autoradiographic study. With dissociation constants (KD) of [3H]AMPA binding and inhibition concentrations (IC50) of L-BOAA, 6-OH-DOPA and L-glutamate obtained from saturation and displacement experiments inhibition constants (Ki) for the inhibition of [3H]AMPA binding in individual hippocampal subregions could be calculated. They were between 5.2 +/- 2.9 and 35.1 +/- 39.9 microM for L-BOAA and 39.1 +/- 26.8 and 59.4 +/- 44.1 microM for 6-OH-DOPA. L-BOAA was equally potent as the endogenous agonist L-glutamate with Ki's between 13.1 +/- 3.9 and 21.4 +/- 12.1 microM (n = 4, mean +/- S.D.). Limbic system symptoms like cognitive deficits, mood disturbances and vivid dreams observed in patients with the motor neuron disease neurolathyrism may thus well be mediated by agonistic action of L-BOAA at AMPA glutamate receptors in hippocampus.

Aged↗
PubMed1994

Quantitative investigations on the human entorhinal area: left-right asymmetry and age-related changes.

The total nerve cell numbers in the right and in the left human entorhinal areas have been calculated by volume estimations with the Cavalieri principle and by cell density determinations with the optical disector. Thick gallocyanin-stained serial frozen sections through the parahippocampal gyrus of 22 human subjects (10 female, 12 male) ranging from 18 to 86 years were analysed. The laminar composition of gallocyanin (Nissl)-stained sections could easily be compared with Braak's (1972, 1980) pigmentoarchitectonic study, and Braak's nomenclature of the entorhinal laminas was adopted. Cell-sparse laminae dissecantes can more clearly be distinguished in Nissl than in aldehydefuchsin preparations. These cell-poor dissecantes, lamina dissecans externa (dis-ext), lamina dissecans 1 (dis-1) and lamina dissecans 2 (dis-2), were excluded from nerve cell number determinations. An exact delineation of the entorhinal area is indispensable for any kind of quantitative investigation. We have defined the entorhinal area by the presence of pre-alpha cell clusters and the deeper layers of lamina principalis externa (pre-beta and gamma) separated from lamina principalis interna (pri) by lamina dissecans 1 (dis-1). The human entorhinal area is quantitatively characterized by a left-sided (asymmetric) higher pre-alpha cell number and an age-related nerve cell loss in pre as well as pri layers. At variance with other CNS cortical and subcortical structures, the neuronal number of the entorhinal area appears to decrease continuously from the earliest stages analysed, although a secular trend has to be considered. The asymmetry in pre-alpha cell number is discussed in the context of higher human mental capabilities, especially language.

Adolescent↗
PubMed1994

Cortical and striatal neurone number in Huntington's disease.

The total cortical and striatal neurone and glial numbers were estimated in five cases of Huntington's disease (three males, two females) and five age- and sex-matched control cases. Serial 500-microns-thick gallocyanin-stained frontal sections through the left hemisphere were analysed using Cavalieri's principle for volume and the optical disector for cell density estimations. The average cortical neurone number of five controls (mean age 53 +/- 13 years, range 36-72 years) was 5.97 x 10(9) +/- 320 x 10(6), the average number of small striatal neurones was 82 x 10(6) +/- 15.8 x 10(6). The left striatum (caudatum, putamen, and accumbens) contained a mean of 273 x 10(6) +/- 53 x 10(6) glial cells (oligodendrocytes, astrocytes and unclassifiable glial profiles). The mean cortical neurone number in Huntington's disease patients (mean age 49 +/- 14 years, range 36-75 years) was diminished by about 33% to 3.99 x 10(9) +/- 218 x 10(6) nerve cells (P < or = 0.012, Mann-Whitney U-test). The mean number of small striatal neurones decreased tremendously to 9.72 x 10(6) +/- 3.64 x 10(6) (-88%). The decrease in total glial cells was less pronounced (193 x 10(6) +/- 26 x 10(6)) but the mean glial index, the numerical ratio of glial cells per neurone, increased from 3.35 to 22.59 in Huntington's disease. Qualitatively, neuronal loss was most pronounced in supragranular layers of primary sensory areas (Brodmann's areae 3,1,2; area 17, area 41). Layer IIIc pyramidal cells were preferentially lost in association areas of the temporal, frontal, and parietal lobes, whereas spared layer IV granule cells formed a conspicuous band between layer III and V in these fields. Methodological issues are discussed in context with previous investigations and similarities and differences of laminar and lobar nerve cell loss in Huntington's disease are compared with nerve cell degeneration in other neuropsychiatric diseases.

Adult↗
PubMed1994

Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study.

Neurotoxic substances are discussed to cause neurodegeneration by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4, 6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease.

Amino Acids, Diamino↗
PubMed1993

Adenosine A1 receptors in human hippocampus: inhibition of [3H]8-cyclopentyl-1,3-dipropylxanthine binding by antagonist drugs.

Adenosine A1 receptors were visualized in human hippocampus using [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as a radioactive ligand probe. The receptor antagonists caffeine, the xanthine derivative KFM 19 and the carbamazepine analogue oxcarbazepine displaced [3H]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). Ki's in the individual layers were in a range between 8.5 +/- 6.5 microM and 18.9 +/- 16.0 microM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. Ki's could not be calculated for oxcarbazepine as the IC50's were greater than 100 microM with estimated IC25's varying between 51.2 +/- 53.3 microM and 179.9 +/- 89.9 microM. Antagonism of endogenous adenosine at A1 receptors may thus explain part of the clinical effects of caffeine in humans and possibly exclusively the behavioral effects of KFM 19 in non-human primates.

Aged↗