Biomedical subjects

Eliza Lewandowska

Publications and source records attributed to Eliza Lewandowska.

13 recordsLinked to original sources

PubMed2006

The brain immune response in human prion diseases. Microglial activation and microglial disease. I. Sporadic Creutzfeldt-Jakob disease.

A study of microglial activation and its contribution to the CNS immune response was performed on the brain autopsy material of 40 patients with definite sporadic Creutzfeldt-Jakob disease (sCJD). Spatial patterns of microglial activation and prion protein disease-associated (PrPd) deposition were compared in cerebellar and cerebral cortices using immunohistochemical (IHC) activation markers. Morphological phenotype forms of microglial cells in activation stages were assessed immunohistochemically (IHC). The immune inflammatory response dominated by microglia was found to be a characteristic feature in CJD. Differences in the intensity and patterns of microglial activation corresponded to variable patterns of PrP deposition, whereas the morphological phenotype forms of microglia were specific for activation stages. The presence of activated microglial cells in the various activation stages regardless of illness duration indicates continuous microglial activity and microglial contribution to the spread of infection for the whole symptomatic period of the disease. Remarkable vacuolar degeneration changes of numerous microglial cells in different activation stages including homing stage may suggest dysfunction of microglial immune surveillance in human sCJD that can significantly contribute to transmissible spongiform encephalopathy (TSE) pathogenesis.

Adult↗

PubMed2006

Ultrastructural picture of blood vessels in muscle and skin biopsy in CADASIL.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is an inherited systemic vascular disorder affecting mainly the central nervous system. We performed detailed ultrastructural examination of the small vessels in the skin and skeletal muscle of a 51-year-old patient with bilateral cerebral white matter lesions, who had a history of two ischaemic strokes. The arterioles were characterized by degeneration and loss of vascular smooth muscle cells (VSMCs). GOM deposits, varied in size and shape, were located in the neighbourhood of the smooth muscle cells, often within an infolding of the cell membrane. No apparent correlations between presence, size or number of GOM deposits and damage severity of vascular smooth muscle cells were seen. Moreover, in some capillaries there were GOM deposits which were seen in the basement membrane near pericytes and endothelial cells. On the other hand, lesions of VMSCs and/or endothelial cells were also visible on the sections of blood vessels devoid of GOM deposits. Genetic tests detected a mutation in exon 4 of the Notch3 gene. It confirmed the initial diagnosis which had been suggested on the basis of the clinical and MRI findings.

Biopsy↗

PubMed2005

Quantitative analysis of activated microglia, ramified and damage of processes in the frontal and temporal lobes of chronic schizophrenics.

Under pathological conditions, microglial cells undergo activation, which is manifested by the expression of histocompatibility locus antigens class II (HLA II) on their surface as well as by proliferation and varied morphological forms. In schizophrenia, characterised by an essential role played by immunological mechanisms, quantitative analysis of activated microglia -- with well-developed ramification (RM), degenerative traits and damaged processes (from their shortening to their complete lack) (DM) -- may contribute to better understanding of schizophrenia etiopathogenesis. Quantitative analysis was performed on slices derived from the frontal and temporal lobes of 9 brains of schizophrenics and 6 control brains. The nonparametric Mann-Whitney U test was used to assess quantitative differences in the distribution of microglia in these regions of the brain. Statistical analyses were performed with STATISTICA 6.5 Programme. In both structures of the brain, the number of activated microglial cells was higher in schizophrenic brains than in control brains. Except for the first layer of the cerebral cortex with the same amounts of RM and DM, the number of DM cells in the remaining regions was several-fold higher than that of RM cells. It is most likely that disturbances in calcium metabolism and energetic balance as well as antibodies produced in the course of schizophrenia are the agents able to trigger a cascade transforming RM into DM. Quantitative differences in RM and DM, observed between the studied structures and cortical regions, could depend not only on functioning of inter-neuronal and inter-structural links. Our study suggests a pivotal role of microglial cells in repair processes and/or etiopathogenesis of schizophrenia and indicates that they undergo substantial damage in the course of chronic schizophrenia.

Adult↗

PubMed2005

Infantile mitochondrial leucodystrophy - a case report.

We retrospectively analyzed a case of a 7-month-old infant with a delay of psychomotor development, slow pupillary light reflexes, horizontal nystagmus, spasticity and bilateral optic nerve atrophy. At the end of life there were problems with swallowing. Ventriculography showed widening of the lateral ventricles and atrophy in the frontal lobes. EEG revealed generalized changes. Clinically, leucodystrophy was diagnosed. General autopsy revealed cardiac hypertrophy. Neuropathological picture showed orthochromatic leucodystrophy with some features characteristic of neuropathology of mitochondrial disease: capillary hyperplasia and hypertrophy, spongiosis and symmetrical, bilateral damage of brain stem structures. The last one is characteristic of Leigh syndrome. Electron microscopic evaluation showed abnormal mitochondria, myelin and neurofibrils destruction. Hypertrophy of the heart may be also connected with mitochondrial disease.

Brain↗

PubMed2005

Sneddon's syndrome as a disorder of small arteries with endothelial cells proliferation: ultrastructural and neuroimaging study.

We report a 18-year-old female patient with livedo reticularis and neurological disturbances. CT scan showed two big ischemic focuses in the pons, moreover MRI revealed small disseminated ischemic focuses in the pons and deep structures of both brain hemispheres. MRA demonstrated no changes in the big extracranial and intracranial arteries. Since the clinical data and neuroimaging results suggested Sneddon's syndrome, the skin and skeletal muscle biopsy was taken to examine. The immunohistochemical and ultrastructural investigations of the skin biopsy revealed a significant reduction of the lumen of the capillaries and small to medium-sized arteries. Cells surrounding the vascular lumen, frequently with multilayer arrangement and their nuclei placed perpendicularly to the lumen, were CD31, CD34, and sporadically SMA positive. At the ultrastructural level, these proliferating cells showed typical features of endothelial cells: abundant intermediate filaments and Weibel-Palade bodies. Between the endothelial cells some junctions were detached as well in the capillaries as in the small arteries. The smooth muscle cells of the small arteries were electron denser than usual and their cytoplasmic protrusions penetrated to the endothelial cells. The ultrastructural picture of some vessels with a considerably narrow lumen was typical of vessels newly formed during angiogenesis. Neuroimaging including TC, MRI, MRA besides histological, immunohistochemical and ultrastructural evaluation may be useful for diagnosis of Sneddon's syndrome.

Adolescent↗

PubMed2004

Ultrastructural evaluation of activated forms of microglia in human brain in selected neurological diseases (SSPE, Wilson's disease and Alzheimer's disease).

Activated forms of microglia were ultrastructurally evaluated in three neurological diseases of different aetiology (subacute sclerosing panencephalitis--SSPE, Wilson's disease and Alzheimer's disease). The occurrence of activated rod, ramified and amoeboid microglia was found in the investigated diseases. The widest ultrastructural variability of microglia was in SSPE, including the presence of mitotic chromosomes or centrioles in its cytoplasm, which indicates microglia proliferation. In the nuclei of activated microglia, some nuclear bodies with different structures were frequently seen, whereas lamellar structures (similar to developing Birbeck's bodies--pathognomonic to Langerhans-type dendritic cells) were observed in the cytoplasm. The activated forms of microglia with apoptotic features were found only in SSPE cases. Some apoptotic nuclei were filled with nucleocapsids of measles virus. In Alzheimer's disease, activated microglia was most frequently bound to senile plaques. Ramified microglia was in contact with amyloid fibrils, which penetrated its cytoplasm and reached the nuclear membrane and channels of rough endoplasmic reticulum, or was situated among dystrophic neurites. Rod microglia was found predominantly at the edge of senile plaques. In Wilson's disease, the ultrastructure of activated microglia showed mostly indirect forms between rod, ramified and amoeboid microglia. The microglia ultrastructure suggests that its morphological form may express functional involvement in the pathogenesis of a given disease entity.

Adolescent↗

PubMed2004

Limbic neuropathology in idiopathic Parkinson's disease with concomitant dementia.

To study pathological background of dementia in idiopathic Parkinson's disease (PD), 41 autopsy brains (31 cases with and 10 cases without dementia) were investigated. The severity of degenerative changes was evaluated in selected limbic regions (trans- and entorhinal cortex, hippocampus, and amygdala). The densities of Lewy bodies (LBs), Lewy neurites (LNs), neurofibrillary tangles (NFTs), and amyloid neuritic plaques (NPs) were determined on immunohistochemically stained sections using antibodies against alpha-synuclein, tau-protein, and amyloid-beta. Precisely defined modern criteria for selecting study cohort (Newcastle, CERAD and Braak et al.) ensured homogeneity of the study sample and reliability of the results. Comparisons between the cases of Parkinson's disease with dementia (PDD) and those without (PD-only) revealed that the former were characterised by significantly higher densities of LBs and LNs in transentorhinal and entorhinal cortices as well as in the CA2-3 region of the hippocampus and cortical complex of amygdala. In the PDD sub-set we found statistically significant correlation of LBs with LNs counts in CA2-3 region of hippocampus as well as of LBs counts in transentorhinal cortex with LNs counts in CA2-3 hippocampal region. The relationship was also observed between LBs counts in CA2-3 region of the hippocampus and LNs counts in cortical complex of amygdala. Our studies suggest that dementia in PD may be associated with the presence of degenerative changes of PD-type in leading limbic structures, without co-existent Alzheimer's disease (AD). They also imply that LBs and LNs may appear to be morphological hallmarks of the pathological process associated with dementia in PD. LBs and LNs distribution pattern and correlations of LBs with LNs counts in limbic regions observed in our study suggest the cumulative patomechanism of changes dependent on transsynaptic alpha-syn pathology and indicate the spread of the pathological process via axonal transport. The coexistence of the small number of changes of AD-type may exacerbate cognitive deficits in PDD.

Aged↗

PubMed2004

Degeneration of microglial cells in frontal and temporal lobes of chronic schizophrenics.

Schizophrenia is a social disease that occurs in 0.5-1% of the population. It shows a high variability in both clinical picture and theory of its pathogenesis. Its clinical manifestations are accompanied by biochemical, immunological and structural changes. A pivotal role in the development of psychotic disorders is attributed to the impaired limbic system. The aim of this study was to find out whether, and if so, to what extent immunocompetent cells of the central nervous system (microglia) are involved in the process of degeneration occuring in these structures. The study was carried out on 12 brains of female chronic schizophrenics. Sections of frontal and temporal cortex were subjected to ultrastructural as well as histochemical and immunohistochemical examinations by light microscopy. In the structures under study, a large number of ramified microglial cells showing on their surface the expression of the major histocompatibility complex class II (MHC II) was observed. Most cells showed degenerative traits (cytoplasm shrinkage, thinning, shortening and fragmentation of their processes) up to apoptotic changes. Perivascular microglia displayed the lowest intensity of degenerative changes. Ultrastructurally, some damaged microglial cells contained phagosomes and/or degenerated mitochondria. Most abnormal microglia showed morphological signs of the former normal function of immunocompetent and phagocytosing cells. Degeneration of microgial cells, resulting most likely from the primary impairment of the neuron-glia communication that damages their immunocompetent function, may lead to the exacerbation of structural damage and psychotic symptoms. Treatment of chronic schizophrenics should involve the supply of agents to prevent degeneration of microglia and/or long-term immunotherapy.

Adult↗

PubMed2003

Neuropathological and anatomopathological analyses of acardiac and "normal" siblings in an acardiac-twin pregnancy.

Acardiac twinning is a very rare complication of multiple pregnancy. The authors present the neuropathological and anatomopathological description of the twins of the multiple pregnancy complicated by the acardiac foetus and terminated at 26 weeks of gestation. An anatomopathological examination of the "normal" twin showed hyaline membrane syndrome, cardiomegaly and hepatomegaly. Neuropathologically, numerous hypoxic-ischaemic lesions, most likely associated with haemodynamic disorders during pregnancy as well as less pronounced perinatal changes were revealed. The acardiac foetus, classified as acardius acephalus, demonstrated the presence of some abdominal organs and a histologically well-developed spinal cord. In view of the neuropathological changes, monitoring "normal" twins for discreet pathological central nervous system signs, which may be similar in character to those described, may play a significant role.

Abnormalities, Severe Teratoid↗

PubMed2003

Dendritic and microglial cells in pups of alcohol-treated female rats.

Alcohol ingestion by female rats during pregnancy and/or lactation leads to developmental anomalies of different organ systems, retardation and immune system impairment in their offspring. In humans, these disorders are termed foetal alcohol syndrome (FAS), or foetal alcohol effect (FAE) if abnormalities are of lesser degree. The study materials consisted of brain, liver and spleen samples collected ten days post partum from neonatal rats born to dams treated with 12% alcohol at a dose of 6 g/kg body mass during pregnancy or during pregnancy and/or lactation. Microglial and dendritic cells were assessed by light (histochemical and immunohistochemical methods) and electron microscopes. Histochemically, the presence of microglia (ramified, amoeboid and rod) and dendritic cells in the studied organs was detected, but only some of them demonstrated the expression of major histocompatibility complex, class I and II (MHC I, II) on their surfaces. Ultrastructural observations revealed immature morphology of part microglial cells, whereas their euchromatin nuclei maybe showed rather high transcription activity. The preliminary study of dendritic cells at ultrastructural level does not indicate pronounced changes. Abnormalities were mostly pronounced in pups born to alcohol-treated dams during pregnancy and during pregnancy and lactation. These observations suggest that microglia and dendritic cells may be regarded as early markers of alcohol-induced impairments. The reduced immune efficiency in animal FAS/FAE models may be due to both immaturity of these cells and low expression of MHC I and II molecules, which renders it difficult for microglial and dendritic cells to present foreign antigens to helper lymphocytes T, which delays the cascade of immune response.

Animals↗

PubMed2003

Degenerative axonal changes in the hippocampus and amygdala in Parkinson's disease.

The morphological background of cognitive and emotional impairments in Parkinson's disease (PD) has not yet been fully explained. We evaluated the expression of synaptic proteins: alpha- and beta-synuclein, synaptophysin and synaptobrevin and ultrastructural changes of perikaryons and axons in limbic structures at post-mortem from cases of PD to estimate degenerative axonal pathology in the hippocampus and amygdala [corrected]. Limbic structures (enthorinal cortex, hippocampus, and amygdala) are essential for the cognitive processes and emotional behaviour. We found that presynaptic axon pathology is mostly connected with hippocampal CA2-3 and dentate hilar regions as well as with the cortical and medio-central complexes of amygdala. Heterogeneous immunoreactivity of alpha-synuclein and diversified ultrastructure of Lewy bodies (LBs) and Lewy neurites (LNs) indicate their consecutive developmental stages. We observed an excessive perineuroneal expression of synaptophysin in the dentate hilar region in all PD cases, except one. This suggests that the dysfunction of synapses in this region may result from axonal pathology. Our study indicates a relation between cognitive and behavioural symptomatology in PD and alpha-synuclein dependent axonal pathology in the hippocampus and amygdala.

Aged↗

PubMed2002

Morphological analysis of active microglia--rod and ramified microglia in human brains affected by some neurological diseases (SSPE, Alzheimer's disease and Wilson's disease).

The activation of microglial cells in pathological conditions is manifested primarily by their proliferation, as well as by the occurrence of a new morphological form--rod microglia. In the present study immunohistochemical identification of rod microglial phenotype against ramified microglia was performed on segments of 17 brains derived from 7 cases of encephalitis of viral aetiology (including 5 SSPE cases), 6 cases of Wilson's disease and 4 cases of Alzheimer's disease. Segments from frontal, temporal and occipital lobes, cerebellum and brainstem were subjected to histological, histochemical and immunohistochemical reactions. The presence of activated rod and ramified microglia was observed in sections derived from all structures of the brains under study. Both morphological forms of activated microglia reacted to antibodies: HLA II, CD68, HAM56 and lectin RCA-1. Expression of HLA II molecules was less intensive on the surface of microglial rod cells. A positive reaction to PCNA antibody was mainly observed in rod/elongated/cylinder-shaped nuclei, which is a characteristic feature of rod microglia. In the study material, the localisation of microglial processes seemed to depend rather on the structural topography of the cell in the brain than on the nuclear shape of the activated microglial cell. Our observations revealed a strong similarity between immunohistochemical phenotypes of both morphological forms of microglia with the indication that rod microglia is a first developmental form of activated microglia.

Adolescent↗

PubMedDate not supplied

Co-existing spinal canal tumours and CADASIL - a diagnostic challenge.

We would like to present a case of a 51-year-old patient with two rare co-existing diseases. The patient was suffering from two tumours in the lumbar region of the spinal canal, which caused development of hydrocephalus. Diffuse white matter hyperintensities (WMH) were observed in our patient's brain imaging. She was also suffering from headaches and she had two mild strokes. We performed some further diagnostic procedures and found out that the patient was suffering from CADASIL. CADASIL was confirmed by both ultrastructural analysis and genetic testing.

CADASIL↗