Morphometric studies of the neuropathological changes in choreatic diseases.

The striatum, pallidum and subthalamic nucleus were studied by combined morphometric methods in serial sections of 13 brains of normal adults and of 15 patients with choreatic diseases. In addition the volume of the hemispheres and of the cortex were measured. All data obtained were corrected by the shrinkage factor to represent fresh brain values. In Huntington's chorea the pallidum was more severely affected than is commonly appreciated. The average volume reduction was of the same degree (lateral-57%, medial-50%) as that of the striatum (-56%). The absolute number of nerve cells of the pallidum decreased in both segments by about 40%. The reduction of the volume and of the number of nerve cells was not reduced in the three subcortical nuclei studied. For the first time it has been shown that there is no increase in the absolute number of glial cells in the striatum. The increased numerical density of glial cells is caused by shrinkage. The loss of nerve cells of the pallidum and subthalamic nucleus is caused mainly by a primary process. Huntington's chorea is a multifocal process. Morphometric data do not suggest that subchorea is a variant of Huntington's chorea. Chorea minor is regarded as a multifocal process with varying affliction of the striatum, pallidum and subthalamic nucleus. An increase in the number of glial cells and, as a rule, a moderate loss of nerve cells were found in this disease.     

Glial and nerve cell changes in rats with porto-caval anastomosis

Summary Nuclear size and density were determined in brain regions with different glial—neurone composition in rats up to 35 weeks after porto-caval anastomosis.In the white matter, i.e. corpus callosum, both the total cell count and the percentage of astrocytes and oligodendrocytes were unchanged.In the corpus striatum, where the glial/neurone ratio is about 1, the number of nuclei registered as astrocytes increased, and after 35 weeks astrocytes comprised 29% of glial cells (compared with 15% in controls). However, the number of oligodendrogial nuclei decreased simultaneously, leaving the total glial number unchanged. In the animals with longest experimental period there was a 15% loss of neurones.In a region with higher glial/neurone ratio, i.e. the Purkinje cell layer, the neurones showed a similar reduction, whereas the number of Bergmann astrocyte nuclei increased less than striatal astrocytes.A small group of animals with pronounced signs of encephalopathy had a higher loss of neurones and, furthermore, the glial number in corpus striatum and callosum was reduced, due to loss of oligodendrocytes.Despite the use of perfusion fixation, the size of astrocyte nuclei increased, this was reversible, as only slight changes were seen after 35 weeks.A possible explanation of the increase in astrocyte nuclear count and decrease in oligodendroglial count could be that nuclei normally considered to the oligodendroglial are transformed into nuclei with morphological characteristics of astrocytes.     

Widespread occurrence of argyrophilic glial inclusions in Parkinson's disease.

Argyrophilic glial inclusions, which are immunohistochemically positive for alpha-synuclein but negative for tau protein, were examined in the brain of Parkinson's disease (PD) patients. Autopsied brains of 10 individuals who died from PD, of two incidental Lewy body disease cases and of five age-matched individuals whose deaths were caused by non-neurological diseases were studied, histopathologically, by Gallyas-Braak staining and, immunohistochemically, with anti-alpha-synuclein antibody, anti-ubiquitin, and anti-tyrosine hydroxylase. All postmortem PD brains showed a significant number of argyrophilic glial inclusions, but no glial inclusions were found in control brains. The inclusions were found not only in the regions showing neuronal loss and gliosis, such as the substantia nigra, locus ceruleus and dorsal vagal nucleus, but also in regions without neuronal loss and gliosis, such as the cerebral cortex, cerebral white matter, striatum, globus pallidus, thalamus, cerebellum and spinal cord. The distribution and density of glial inclusions in PD brains varied from case to case but, in the cerebral cortex, the number of glial inclusions were fairly well correlated with the number of Lewy bodies. The distribution pattern of glial inclusions also showed a striking resemblance to that of catecholaminergic neurones and fibres. The abnormal accumulation of alpha-synuclein in glial cells was more widespread than neurone loss, and appears to be an important pathological feature of PD.     

The distribution of glial fibrillary acidic protein and vimentin in postnatal marmoset (Callithrix jacchus) brain

Antisera to glial fibrillary acidic protein (GFAP) and vimentin were used to elucidate the distribution of these intermediate filament proteins in postnatal marmoset brains of various ages. The ependyma of the lateral ventricles was unique in being equally immunoreactive for both GFAP and vimentin at all ages. Vimentin alone was consistently demonstrated in endothelial and leptomeningeal cells at all ages. In neonates, vimentin immunoreactivity greatly exceeded that of GFAP and was located primarily in radial glia in the subependymal plate of the anterior cerebrum. Their vimentin-positive processes formed thick fascicles in the corpus callosum but separated into fine fibres on entering the cortex. GFAP immunoreactivity in these cells and processes was very limited. With age, GFAP-positive cells increased in number and displayed the typical stellate appearance of astroglia. The vimentin-positive radial glial population decreased considerably during this period and by 6 months had virtually disappeared. The GFAP reaction in adult brain was even more widespread, largely due to the increased number of positive astrocytes in the white matter. Vimentin immunoreactivity in the adult was greatly diminished and positive radial glia were not detectable. A major change in intermediate filament protein expression, therefore, occurs in the early postnatal period and probably reflects phases in the differentiation of radial glial precursors into astrocytes.     

成人脑神经干细胞体内外增殖、分化和迁移研究

目的探索从成人脑组织获取的神经干细胞（成人-hNSCs）在体外的增殖能力、分化特性、以及在裸鼠颅内的存活、迁移及分化情况。方法分别留取癫痫患者手术切除的颞叶脑组织和10W左右人类自然流产胎儿纹状体组织,体外分离成单细胞悬液,无血清培养基培养、传代并诱导分化。软琼脂糖集落形成实验检测NSCs的增殖能力。免疫荧光法检测NSCs标志物神经上皮巢蛋白（Nestin）和诱导分化后神经元标志物13．tubllin以及神经胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达;利用动物立体定向仪将体外悬浮培养2W的人NSCs移植入裸鼠颅内,检测NSCs在裸鼠脑组织局部的存活、迁移和分化状况。结果成人-hNSCs集落形成能力较胚胎脑组织来源的NSCs（胎儿-hNSCs）明显减弱,免疫荧光染色显示分离的NSCs呈Nestin阳性,诱导分化后可见（β-tubllin和GFAP阳性的神经细胞,其中80％的细胞为GFAP阳性的星形胶质细胞,20％左右为β-tubllin阳性细胞。分别将成人-hNSCs和胎儿．hNSCs移植入裸鼠纹状体,1个月后,冰冻切片,荧光显微镜观察到来源于成人脑组织来源的NSCs仅见沿针道的近距离迁移,免疫荧光染色在成人-hNSCs移植裸鼠颅内只检测到GFAP阳性的星形胶质细胞。而胎儿-hNSCs可穿过针道,沿大脑廉向脑实质广泛迁移,免疫荧光染色能检测到GFAP和少量（β-tubllin阳性细胞。结论成人脑组织和胚胎纹状体组织中均能成功分离到神经前体细胞,而与胎儿．hNSCs相比,成人-hNSCs体外增殖能力、多向分化潜能和体内迁移能力都明显减弱。     

Age-related decrease of the perineuronal satellite cell number in the rabbit spinal ganglia

This study was undertaken to establish whether a change in the perineuronal satellite cell number contributes to the age-related reduction of the volume ratio between the perineuronal glial sheaths and their associated nerve cell bodies, observed to occur in rabbit spinal ganglia. The volumes of the nerve cell bodies and the numbers of the related satellite cell nuclei were estimated on serial semithin sections from young adult and old rabbits. As satellite cells are mononucleate, the number of the nuclei corresponds to that of these cells. The satellite cell sheaths in both age groups were also examined under the electron microscope. The mean number of satellite cells was significantly smaller in the aged animals than in the young adults although the mean volume of the nerve cell bodies was significantly larger in the former. Cytoplasmic vacuoles, invaginations of the connective tissue and autophagic vacuoles were more frequent in the old rabbits. Satellite cells with pyknotic nuclei and remnants of degenerated satellite cells were only found in aged animals, although rather rarely. The decrease in the satellite cell number is one of the mechanisms by which the age-related reduction of the volume ratio between the perineuronal glial sheaths and their associated nerve cell bodies takes place. The decrease in the satellite cell number seems to occur, at least in part, through cell degeneration. However, other mechanisms (e.g., detachment of satellite cells from the perineuronal sheaths) cannot be excluded. Since satellite cells play a role in neuronal support, the significant decrease in their number probably has negative consequences for neuronal activity.     

Transplantation of bulk-separated oligodendrocytes into the brains of shiverer mutant mice: Immunohistochemical and electron microscopic studies on the myelination

Normal oligodendrocytes were separated from 7-day-old mouse (BALB/c) brains by the Percoll gradient method. Immunohistochemical staining with an anti-galactocerebroside serum revealed that about 85% of the separated cells were oligodendrocytes. The oligodendrocytes were transplanted into the corpus striatum of 4-week-old shiverer mutant mice which are characterized by the lack of myelin basic protein (MBP). Myelination by the implanted oligodendrocytes was investigated immunohistochemically and electron microscopically 6 weeks after operation. Certain areas in the corpus striatum were intensely stained with antiserum to MBP. Electron microscopic examination showed that some axons were surrounded by normal type myelin sheaths with major dense lines. These results clearly indicate that matured oligodendrocytes are able to survive and myelinate the host axons even in the adult brain.     

Morphological evidence for direct interaction between gonadotrophin-releasing hormone neurones and astroglial cells in the human hypothalamus

In rodents, there is compelling evidence indicating that dynamic cell-to-cell communications involving cross talk between astroglial cells (such as astrocytes and specialised ependymoglial cells known as tanycytes) and neurones are important in regulating the secretion of gonadotrophin-releasing hormone (GnRH), the neurohormone that controls both sexual maturation and adult reproductive function. However, whether such astroglial cell-GnRH neurone interactions occur in the human brain is not known. In the present study, we used immunofluorescence to examine the anatomical relationship between GnRH neurones and glial cells within the hypothalamus of five women. Double-staining experiments demonstrated the ensheathment of GnRH neurone perikarya by glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte processes in the periventricular zone of the tuberal region of the hypothalamus. GFAP immunoreactivity did not overlap that of GnRH at the GnRH neurone's projection site (i.e. the median eminence of the hypothalamus). Rather, human GnRH neuroendocrine fibres were found to be closely associated with vimentin or nestin-immunopositive radial glial processes likely belonging to tanycytes. In line with these light microscopy data, ultrastructural examination of GnRH-immunoreactive neurones showed numerous glial cells in direct apposition to pre-embedding-labelled GnRH cell bodies and/or dendrites in the infundibular nucleus, whereas postembedding immunogold-labelled GnRH nerve terminals were often seen to be enwrapped by glial cell processes in the median eminence. GnRH nerve button were sometimes visualised in close proximity to fenestrated pituitary portal blood capillaries and/or evaginations of the basal lamina that delineate the pericapillary space. In summary, these data demonstrate that GnRH neurones morphologically interact with astrocytes and tanycytes in the human brain and provide evidence that glial cells may contribute physiologically to the process by which the neuroendocrine brain controls the function of GnRH neurones in humans.     

Human amniotic epithelial cells express specific markers of nerve cells and migrate along the nerve fibers in the corpus callosum

Human amniotic epithelial cells were isolated from a piece of fresh amnion. Using immunocytochemical methods, we investigated the expression of neuronal phenotypes (microtubule-associated protein-2, glial fibrillary acidic protein and nestin) in human amniotic epithelial cells. The conditioned medium of human amniotic epithelial cells promoted the growth and proliferation of rat glial cells cultured in vitro, and this effect was dose-dependent. Human amniotic epithelial cells were further transplanted into the corpus striatum of healthy adult rats and the grafted cells could integrate with the host and migrate 1-2 mm along the nerve fibers in corpus callosum. Our experimental findings indicate that human amniotic epithelial cells may be a new kind of seed cells for use in neurograft.     

Cellular distribution of the GABAA receptor-modulating 3alpha-hydroxy, 5alpha-reduced pregnane steroids in the adult rat brain

The 3alpha-hydroxy,5alpha-reduced pregnane steroids, allopregnanolone and allotetrahydrodeoxycorticosterone, are the most potent endogenous positive modulators of GABA(A) receptor-mediated inhibition. This study presents the first immunohistochemical examination of the cellular distribution of 3alpha-hydroxy,5alpha-reduced pregnane steroids across the brain. We found a widespread distribution in the adult rat, with dense immunolabelling in the olfactory bulb, striatum and cerebral cortex, and lower density labelling in the brainstem reticular formation. In general terms, this distribution accords with the regional concentrations of 3alpha-hydroxy,5alpha-reduced steroids determined, in other laboratories, by brain region sampling and either gas chromatography-mass fragmentography or radioimmunoassay. However, immunohistochemistry allowed for a more detailed examination of regional distribution and cellular specificity. All immunoreactivity was confined to the cell bodies and thick dendrites of neurones; no identifiable glia were labelled. In most brain areas, the location and morphology of labelled cells identified them as excitatory neurones. In addition, cell populations known to be projecting GABAergic neurones (e.g. cerebellar Purkinje cells) were immunoreactive, whereas local inhibitory neurones generally were not. The cellular distribution of 3alpha-hydroxy,5alpha-reduced steroids suggests that sensory, motor, limbic and homeostatic systems can be influenced by neurosteroids at multiple stages of processing.     

Morphometrical-statistical structure analysis of human striatum, pallidus and subthalamic nucleus. II. Globus pallidus]

1. The pallidum of 13 hemispheres of 11 human brains of normal adults was studied by morphometric-statistical methods. 2. The values obtained on paraffin-embedded frontal serial sections were corrected individually for shrinkage in order to get comparable fresh values. 3. The mean fresh volume of the pallidum laterale of males (1220 mm3) was 13% higher than that of females (1065 mm3). The corresponding mean values of the pallidum mediale were 520 mm3 (male) and 430 mm3 (female), the difference being 17%. The difference between sexes failed to be significant. The lateral segment accounted for about 70% of the total volume of the pallidum. 4. The pallidum occupied 0,32% or ca. 1 over 300 of the volume of the hemisphere. 5. The numeric cell densities showed no significant age or sex differences. The mean value of the lateral pallidum was 437 nerve cells/mm3 and of the medial part 327 nerve cells/mm3, the difference being highly significant (p less than 0,001). 6. The pallidum laterale showed a numerical density of 66000 glial cells/mm3, the medial segment had 62000 glial cells/mm3, the difference just reaching the 5% -- level of significance. 7. On the average the ratio of glial cells to nerve cells was 158:1 in the lateral pallidum, and 159:1 in the medial part. The difference was statistically significant (p less than 0,01). 8. The mean of the total number of nerve cells in the pallidum laterale amounted to 540000 for males and 465000 for females. The corresponding values of the medial part were 171000 (male) and 143000 (female). The total number of pallidal nerve cells is just about as high as the number of large striatal nerve cells (670000 (male) and 570000 (female). 9. In the pallidum laterale we calculated the total number of glial cells to be 82 million for males and 63 million for females. In the medial pallidum we found 32 million (male) and 26 million (female). 10. The total numbers of nerve and glial cells were well correlated in the lateral as well as in the medial segment (r = 0,636 and r = 0,734, respectively). 11. The volumetric nerve cell densities showed no significant differences between sexes. The values were 0,36 Vol.-% lateral and 0,31 Vol.-% medial. This difference failed to be significant. 12. The volumetric densities of the glial cell nuclei were equal in both segments, the value being 0,43 Vol.-%. They were strictly correlated (r = 0,830). 13. The mean volume of a nerve cell in the medial segment (9600 mum3) was 19% higher (p less than 0,05) than in the lateral segment (8100 mum). 14. The mean volume of a nucleus of a glial cell showed only insignificant differences, being lateral 65 mum3 and medial 70 mum3. 15. The various morphometric data indicated a closer correlation between striatum and pallidum laterale than between striatum and pallidum mediale. Within the striatum, the putamen showed a better correlation with the pallidum than the nucleus caudatus.     

Distribution of luteinizing hormone-releasing hormone in the nervus terminalis and brain of the mouse detected by immunocytochemistry

Immunoreactive luteinizing hormone-releasing hormone (LHRH) was localized in a relatively large number of ganglion cells and fibers of the nervus terminalis of neonatal and adult mice, indicating that this nerve is a substantial source of LHRH in the mouse brain. Whole-head specimens of neonatal mice, prior to calcification of the cranium, revealed an extensive distribution of LHRH neurons and fine fibers throughout the peripheral, intracranial, and central parts of the nervus terminalis. The most striking difference between the neonatal and adult animals, in the nervus terminalis, was the increase in immunoreactive axons that made up the fiber bundles of this nerve. In the adult mouse, the intracranial and central projections were composed of thick fascicles of immunoreactive axons, ensheathed by glial cells and accompanied by ganglia that contained both LHRH-reactive and nonimmunoreactive neurons. LHRH-immunoreactive cells and axons were seen in a branch of the nervus terminalis that coursed along the medial, posterodorsal aspect of the olfactory bulb and in branches of this nerve that accompany the vomeronasal nerves to the accessory olfactory bulb. A few LHRH neurons and many immunoreactive processes were seen in the accessory and main olfactory bulbs. LHRH-reactive neurons were seen in the hypothalamus and extrahypothalamic structures. Examination of adult mouse brains revealed a pattern of distribution and number of immunoreactive neurons similar to that seen in the neonate. However, many more LHRH-reactive axons were seen in all areas of the brain of the mature animal.     

Differentiation of transplanted neural precursors varies regionally in adults striatum

In the current experiments, we address the emerging hypothesis that transplanted neural precursor cells can respond to local microenvironmental signals in the post-developmental brain and exhibit patterns of differentiation that depend critically on specific location within the brain. HiB5 precursor cells were transplanted into adult mouse cortex, corpus callosum, and multiple positions in striatum, and assessed for differentiation by morphology and immunocytochemistry. Our results indicate that the likelihood of both neuronal and glial differentiation of transplanted precursors depends on proximity to the medial striatum or subventricular zone of the adult host, supporting the concept that microenvironmental signals can critically affect the differentiation fate of neural precursors, and suggesting the potential to manipulate such signals in the adult brain.     

Comparative migration and development of astroglial and oligodendroglial cell populations from a brain xenograft.

In previous studies of brain transplantation, the fate of the implanted glial cells has been investigated separately; that is, the interest has been focused either on the astroglia or on the oligodendroglia. However, the two populations of implanted glial cells may interact with each other, for example by secreting species-specific factors or by inducing reactions by the host. We have used two different models of brain transplantation: one that allows the identification of the implanted astrocytes, and another that allows the identification of the implanted oligodendroglia. The present model is a combination of both; it consists of the grafting of embryonic rabbit brain fragments into the brains of neonatal Shiverer mice. The myelin made by the implanted oligodendrocytes is identified by anti-myelin basic protein immunohistochemistry. The implanted astrocytes are identified by a monoclonal antibody that combines with rabbit but not with mouse glial fibrillary acidic protein. This study shows that although they use the same major routes of migration, both populations of glial cells tend to move differently. They demonstrate areas of common settlement but also areas where only one population of implanted glia is present. From the site of implantation in the dorsal striatum, the major routes of migration are the corpus callosum, the white matter fascicles in the striatum, and the internal capsule. After a delay of 6 weeks, no significant prevalence of one population of implanted glial cells over the other was observed.     

Distribution of protein-bound radioactivity in brain slices of the adult rat incubated with labelled leucine.

The distribution of protein-bound labelled leucine in brain cortex slices, prepared from adult rats by various methods and incubated with [14C]- or [3H]leucine, was investigated by autoradiography. In the first and second slices a marked gradient of incorporated radioactivity from the cut surface to the slice interior was observed. Very high labelling of leptomeningeal cells and vessels enhanced further the inhomogeneity of radioactivity distribution. Light microscopic examination of incubated slices revealed morphological alterations of neurones, especially in the vicinity of the cut surface. The comparison of grain density over neurones and their satellite glia indicated markedly higher incorporation into the latter. The ATP level in slices at the end of incubation reflected the method of slice preparation and morphological integrity. Inhomogeneity of incorporated radioactivity distribution in brain slices contrasted with the uniform labelling of cortical cells in vivo, and may represent at least one reason for the low estimates of protein synthesis rate in brain cortex slices.     

Precocious synapses in 13.5-week fetal holoprosencephalic cortex and cyclopean retina

Background: Genetic programming of cerebral development involves tissue morphogenesis and also timing of developmental processes. Precocious synaptogenesis in the neocortical plate was previously demonstrated in 5 of 6 fetuses of 20–31 weeks gestation. Materials and methods: Neuropathological examination was performed of a 13-week-5-day fetus with trisomy-13, alobar holoprosencephaly, hydrocephalus, cyclopia and absence of ears. Immunocytochemical demonstration of the synaptic vesicle protein synaptophysin was performed in the brain and retina, along with other neuronal markers. Results: Synaptophysin reactivity in the cortical plate was patchy and precocious. Radial glial fibres, demonstrated by vimentin, were oriented parallel to the cortical plate rather than perpendicular, probably because of hydrocephalus. A corpus striatum was not identified, but the poorly formed thalamus exhibited synaptophysin reactivity around many neurones. The cyclopean eye had ocular features of maturational delay including persistent hyaloid artery; ganglion cells were reduced in number, but retinal synaptophysin reactivity was paradoxically precocious. Conclusions: Holoprosencephaly exhibits abnormal patchy synapse distribution in the neocortex and retina; synaptogenesis was precocious, as we previously described in older fetuses. Too soon an onset of synapse formation may promote early epileptic circuitry, leading to severe infantile epilepsies postnatally. The visual system is the last of the special sensory systems to mature, yet in this case showed too early synapse formation. In HPE, cyclopia and in trisomy 13, total absence of external ears has not been reported; it results from faulty craniofacial induction by neural crest.     

Light and electron microscopic characterization of the evolution of cellular pathology in the R6/1 Huntington's disease transgenic mice

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of CAG repeats in the Htt gene. Examination of the post-mortem brains of HD patients shows the presence of diffuse nuclear htt immunoreactivity and intra-nuclear inclusions. The aim of this study was to produce a detailed characterization of the neuronal pathology in the R6/1 transgenic mouse model. The R6/1 carrier mice demonstrate intra-nuclear and extra-nuclear inclusions with the S830 htt antibody at 2-11 months of age. The distribution pattern of neuronal intra-nuclear inclusions (NIIs) was irregular in several brain regions including the striatum, cortex and hippocampus. A greater number of NIIs were found in the ventral striatum than in the dorsal striatum. In the globus pallidus, cerebellum and thalamus the pattern of inclusion formation was relatively consistent over time. At 4 and 6 months of age, the R6/1 mice showed increased glial fibrillary acid protein (GFAP) immunoreactivity in the cortex compared to their wildtype littermates, yet no difference was found in the striatum. Analysis by electron microscopy found that neurons from the R6/1 carriers contained a densely packed cytoplasm at 1.5 months of age, with some neurons displaying structural abnormalities including vacuolization and nuclear membrane folding. No NIIs were detected at this age, but by 7 months of age, NIIs were present with severe cellular vacuolization. The present study indicates that a decrease in striatal volume with cell loss is present in young (2 months) R6/1 mice, and the distribution of NIIs is robust and widespread, with considerably temporal and spatial variation in NII development between mice.     

Collagen-cliondroitin-6-sulfate hydrogel implants in CNS lesion cavities favor glial repair, the differentiation of co-implanted neurons and the growth of axons

Collagen chondroitin-6-sulfate hydrogels containing embryonic striatal neurons were implanted into premade brain cavities of the rat striatum. The bioimplant was progressively transformed into a new matrix mostly by the deposition of newly formed collagen and by the ingrowth of glial cells and glial cell processes. At two months, the new matrix has partly restructured the lesion cavity. Cells co-implanted with the hydrogels attached, survived and differentiated while nerve fibers of the host striatum grew into the biomatrix.     

Neurotransmitter distribution in the second trimester fetal human corpus striatum

One experimental strategy that may offer hope in the neurodegenerative disorder Huntington's disease (HD) has been neural transplantation. In HD, most of the pathological changes occur in the corpus striatum. Fetal human striatal implants will most likely be the first transplant strategy attempted in clinical trials to replace lost neurons and/or prevent the degeneration of neurons destined to die. The temporal expression of neurotransmitters in the developing human corpus striatum is a key factor in determining the optimum age of transplantable tissue. To this end, an immunocytochemical analysis of various neurotransmitters was performed on second trimester human brains. Antibodies against acetylcholine, gamma-aminobutyric acid, enkephalin, neuropeptide-Y and substance P were used in ten human fetal brains ranging from 13 to 21 weeks gestation. The presence and pattern of distribution for these neurotransmitters varied in the different parts of the corpus striatum (globus pallidus, putamen, caudate nucleus). These results are compared to the already existing data for the adult human corpus striatum.     

Histopathology and fine structure of the brain in six cases of Creutzfeldt-Jakob disease from western India.

Light and electronmicroscopic changes in 5 formalin-fixed brains, and one glutaraldehyde-fixed brain biopsy, from patients with Creutzfeldt-Jakob disease in the age range of 45 to 65 years, are described. These 6 patients (out of 7 reported clinically earlier and 2 unreported) had classical manifestations with progressive dementia, pyramidal signs and myoclonic jerks. Light microscopy showed neuronal and nerve fibre loss, moderate or severe spongiform change, astrocytic proliferation and absence of inflammatory reaction. Electronmicroscopy confirmed the characteristic membranous profiles of the 'cysts' and 'daughter cysts' constituting the spongiform change. The membranes were generally dark and thin, either concentrically arranged or splitting and with stray pale broad segments. The one glutaraldehyde-fixed brain biopsy specimen showed cisterns of RER in close proximity to these 'cysts', suggesting the source of proteinous material of these membranes. Though mainly in the neurones and dendrites of the cortex, at times they were seen in the myelinated fibres also, a few of which showed dystrophic axons bearing dense bodies. One of the 6 patients had cerebellar signs also, and a total duration of the neurological illness of 36 months, as against 2-8 months in the 5 other patients. The histopathological examination of her brain revealed less spongiform change, and many cerebral cortical glial whorls, the centre of which showed PAS-positive and congo-red-positive material representing amyloid. Fine structural examination confirmed the glial whorls, and the filamentous nature of amyloid in the plaques, which resembled Kuru plaques. All brains also showed more or less intraneuronal lipofuscin.