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.
The autopsy findings in 3 cases of type I ("classical") and 3 of type II ("hydrocephalic") lissencephaly are presented. The characteristic pathomorphology is described and some aspects about pathogenesis are considered.
The cathepsin B, D and L were studied by immunohistochemical techniques in the human postmortem brain. The enzyme were primarily localized in neurons. Makroglial cells were seldom immunostained. It is shown that cathepsins B and D frequently occur in neuritic plaques of Alzheimer victims, thereby raising the question, whether or not cathepsin immunohistochemistry is a useful tool in the diagnosis of this disease. Furthermore, we identified certain glial cells to be immunoreactive for cathepsins in schizophrenics.
The development of fluctuations in disability are a main problem of the levodopa long-term treatment in Parkinson's disease. The early combination of low doses of levodopa with a dopamine agonist as lisuride improves the symptoms of Parkinson's disease as much as a monotherapy but prevents the development of fluctuations in disability and dyskinesias at the same time.
Malignant angioendotheliomatosis, so called intravascular malignant lymphomatosis or angiotropic lymphoma, was found in cerebral hemispheres, spinal cord and nerve roots of a 50-year-old woman who died 4 months after onset of neurological symptoms. The pathological findings were characterised by neoplastic cells within the lumina and wall of small vessels as well as by multiple infarcts in the CNS. Vascular occlusions were caused by tumor cells and secondary changes of the wall. Positive reactions of Common Leucocyte Antigen and B-cell-markers support the idea of a lymphoid origin for the tumor cells. The differentiation to the angiocentric lymphoma as a T-cell tumor and the obscure pathogenesis of this neoplastic process must be clarified in the future.
Specimens from the area 10 of the frontal cortex collected out of 7 patients with severe mental retardation, aged 3 to 24 years and also 8 non-neuropsychiatric age-matched controls were processed according to the Golgi-Kopsch method. The total length of the apical side-dendrites and of the basal dendrites was measured on layer V pyramidal neurons. Compared with controls the total dendritic length of the apical side-dendrites as well as of the basal dendrites was significant reduced in the affected patients (p less than 0.001). The reduced dendritic length represents perhaps a morphological correlate to the mental dysfunction.
Parvalbumin and calbindin, two calcium binding proteins in the nervous system, are present in certain neuronal subpopulations. In the present study a method for a simultaneous demonstration of the both antigens was developed, which labels parvalbumin- and calbindin-containing structures in contrasting colours. A horseradish peroxidase-conjugated second antibody was used for the visualization of the monoclonal anticalbindin antibody, whereas the biotinylated anti-parvalbumin antibody was demonstrated by means of a biotin-streptavidine-alkaline phosphatase system. The method may be useful to classify neuronal populations and to study their morphological relationship.
The presented methodical contribution demonstrates the suitability of rhodamine-labelled latex microspheres with a defined mean diameter of around 20 nm for retrograde neuronal tracing. After small injections of about 200 nl red fluorescent tracer into visual cortex of mice afferent neurons were labelled in cortical and subcortical structures. Basal forebrain neurons containing the tracer were further characterized by the concurrent visualization of choline acetyltransferase, a marker for cholinergic neurons, and parvalbumin, a putative marker of GABAergic neurons, by immunofluorescence.
Dementia due to vascular and degenerative abnormalities has become more frequent with increasing life expectancy. Although the origin of both dementia types is still unknown, pathobiochemical perturbations comprising energy loss, lactic acidosis, calcium homeostasis and free radical formation have been found in both dementia types in incipient stages at the neuronal level. A therapeutic rational against these abnormalities is discussed.
The distribution of intermediate filaments GFAP, Vimentin and Desmin was investigated in normal intracerebral and meningeal vessels in human material. Vimentin is detectable in endothelial cells of all cranial vessels. Moreover Vimentin is expressed in all vascular smooth muscle cells of the brain with the exception of arterioles in the white matter and in the pons. Desmin is only detectable in the tunica media of larger intracerebral arterioles or arteries, larger meningeal veins contain single Desmin positive smooth muscle cells. Immuno-electronmicroscopically Vimentin could be shown in endothelial and smooth muscle cells of larger venous and arteriolar vessels. We conclude from our immunohistologic investigation that there is an uneven distribution of Vimentin and Desmin in brain vessels which might reflect some ultrastructural peculiarities of brain arteries.
The content of the polyamines putrescine, spermidine and spermine, and the activity of their metabolic key enzyme ornithine decarboxylase (ODC) were measured in tissue samples obtained during operation of 45 patients with primary or recurrent gliomas, meningiomas and pituitary adenomas. Biochemical analysis and histopathological classification were carried out in the same tumor samples. In benign tumors ODC activity was less than 10 nmol/g/h, whereas in malignant gliomas values up to 34 nmol/g/h were observed. In rapidly growing tumors pronounced heterogeneity was observed with high values in solid tumor parts and low values in necrotic areas. Thus, high ODC activity represents a reliable biochemical marker of malignancy in brain tumors, but low values do not prove benignity.
A retrospective study was conducted into 37 brains of patients, who had died of Grade 2-4 glioma. For assessment of morphological signs of hemorheological failure, microcirculation was checked by H & E, Klüver-Barrera, and Goldner staining as well as by staining for fibrin, using a modified technique according to Zerbino and Lukasewitsh. Microthrombosis was recorded from 30 in the above 37 brains, all of them related to patients with Grade 3 glioma and glioblastoma. Fibrin thrombi represented the predominant variant of microthrombosis. They exhibited differentiated characteristics depending on their localisation in the central and the peripheral regions of the tumour or in surrounding brain tissue. Also included in the study were rates of vascular proliferation and types of necrosis as well as relations between these and microthrombi. The role played by microthrombi in such cases of glial tumours is discussed in some detail.
Pyloric biopsies obtained at pyloromyotomy from 46 infants were studied by light and electron microscopy and compared to 8 autopsy control cases without any evidence of infantile hypertrophic pyloric stenosis (IHPS). A positive family history of this disorder was recorded in 8 cases (2 girls and 6 boys). The most frequent changes in the myenteric plexus comprised axonal alterations. In glial cells, cytoplasmic vacuolisation or an increase of intermediate filaments occurred. In ganglion cells, vacuolisation of perikaryal cytoplasm or dense bodies were observed. No obvious differences were seen between sporadic and hereditary cases. In addition to these fine structural alterations, immunohistochemistry in 6 IHPS cases and 4 controls revealed differences in the distribution of substance P, bombesin, calcitonin gene related peptide and enkephalin-like immunoreactivity within the myenteric plexus between IHPS and control cases. The immunoreactivity, however, was unevenly distributed from case to case and even within individual cases. The reduction of immunoreactivity corresponded, at least in part, to an increase of neurofilaments or abnormal organelles within axons. Increased immunoreactivity was apparently related to focal accumulation of dense cored vesicles noted in the preceding study. It is suggested that these and other changes reported interfere with the normal gastrointestinal reflex mechanisms leading to intestinal obstruction.
On the basis of experimental set-ups in vitro and in vivo and by making use of specific autoradiographical techniques, the following data on the proliferation of astrocytes from newborn rats in vitro and unpretreated rats and mice in vivo could be obtained: (i) The commonly employed immunohistochemical staining techniques in vitro are not applicable in tissue sections. (ii) In vivo, astrocytes show increasing durations of cell cycle (tc) as well as S phase (ts) prenatally until about birth. A similar trend can be observed in vitro. However, the absolute values for ts and tc can be substantially modified depending on the culture conditions. (iii) As regards the mode of proliferation, astrocytes in vitro grow exponentially and without transition of quiescent cells from the non-growth fraction into the growth fraction (GF). In contrast, astrocytes in vivo exhibit steady-state growth and continuous recruitment of proliferating cells from the non-GF. These differences show that there is a need for further in vivo-experiments when studying new strategies in the treatment of gliomas.
In situ hybridization histochemistry opened new perspectives for the study of viral infections of the central nervous system. Immunohistochemistry can give information about the presence of a viral infection only, if the specific viral proteins are expressed in the infected cells, while in situ hybridization can detect viral genes also in case of a latent, non-productive infection. The basic technique has to be modified according to the kind of viral nucleic acid to be displayed (genomic DNA, plus or minus strand genomic RNA, viral mRNA). For detection, the highly sensitive radioactive or the less sensitive non-radioactive (enzyme-) labels can be applied. For the determination of the cell type harbouring the virus and for correlation of viral nucleic acids with viral proteins, in situ hybridization techniques and immunohistochemistry have to be combined.
The silver staining of interphase nucleolar organizer regions (NORs) is a recently developed method to measure cell proliferation in tissue specimens. The major silver staining protein is nucleolin, a 92 kd nucleolar protein, which probably controls rDNA transcription. Nucleolin itself is under control of p34cdc2 kinase, which is a subunit of M phase kinase. The specific silver staining of NORs measures ribosomal gene activity and is therefore useful in measuring cell proliferation via nucleolar biosynthetic activity. Although human tumors of different malignancy grades usually can be distinguished by their AgNOR number, there is considerable overlap between different grades which significantly hampers their use in individual cases. For routine application of the AgNOR technique in histopathology we propose a standardised staining protocol with use of internal control cells and the use of image analysis for AgNOR enumeration.
This report concerns a 11-year-old girl--at the time of death--who developed normally until the age of 2 years when further psychomotoric maturation stopped and then regressed. The disease was diagnosed as neuroaxonal dystrophy (NAD) by sural nerve biopsy at the age of 7. Further course was characterized by complete loss of all motoric and sensory functions and dementia as well. Finally there was decerebration. The autopsy revealed generalized NAD associated with pallidal deposition of iron pigment to classify as generalized intermediate NAD type II according to Gilman and Barrett (1973). The main histological findings were axonal swellings and spheroids consisting ultrastructurally of membrano-tubular profiles, lamellar structures, vacuoles, glycogen granules and mitochondrial aggregates. Immunohistologically there was partial positive expression of synaptophysin and neurofilament protein in the spheroids. Firstly described electron microscopical findings in the retina include the typical axonal lesions largely in interior layers. Photoreceptors and their synaptic contacts were preserved. The present blindness is of the neuronal type. The current etiopathogenetic opinions, aspects of bioptic diagnosis and problems of classification of primary NADs are discussed.
The arterial distensibility and the modulus of volume elasticity of more than 100 isolated human carotid arteries was measured and correlated with arteriosclerosis and aging. The loss of arterial distensibility progresses steadily with aging. Arteries with severe arteriosclerosis and arteries with minimal arteriosclerosis show almost similar distensibility. On the other side the differences between distensibility of arteries with moderate arteriosclerosis and arteries with minimal as well as severe arteriosclerosis, especially in the younger and middle ages, are significant.
Histoautoradiographic and immunohistochemical studies of biopsies from 27 brain tumors yielded the following preliminary conclusions: 3H-thymidine labeling indices and Ki-67 growth fraction indicate the proliferative activity more reliable than counting of mitoses, the fraction of DNA synthesizing tumor cells and the Ki-67 growth fraction show an equal behaviour, as expected, the immunohistochemical values are higher than the labeling indices because all tumor cells within the proliferation cycles express the nuclear antigen. By the increase of the number of tumors and the use of the different cell kinetic methods on the same tumor tissue the prerequisite to grading of brain tumors as a basis of therapeutic strategy can be improved.
