Biomedical subjects

Dorota Dziewulska

Publications and source records attributed to Dorota Dziewulska.

10 recordsLinked to original sources

PubMed2006

Role of endoglin and transforming growth factor-beta in progressive white matter damage after an ischemic stroke.

We morphologically examined human brains several years after a territorial ischemic stroke to assess the development of progressing white matter damage and its pathomechanisms. Our investigations focused on the role of TGF-beta, one of the factors whose expression increases after tissue damage, and its receptor endoglin in the propagation of postischemic injury. Examination of the white matter adjacent to the postapoplectic cavity revealed structural changes in the capillary vessels, disturbed microcirculation, and deep endothelial cell damage with DNA fragmentation in the TUNEL reaction. Many oligodendrocytes also revealed DNA damage and an increased expression of caspase-3. In the rarefied white matter, the microvessel immune reaction to TGF-beta was diminished while the expression of endoglin was heterogeneous: absent in some capillaries but increased in others in comparison to the vessels located more peripherally from the cavity and in the control material. We conclude that endoglin and TGF-beta can be involved in the development of the microangiopathy responsible for the propagation of postischemic white matter injury in humans. We suggest that disturbances in endoglin expression can influence TGF-beta signaling and, consequently, vessel structure and function. Pronounced endoglin expression can lead to decreased vessel wall integrity while a lack of the constitutively expressed protein is probably a mirror of deep vessel damage.

Aged↗

PubMed2006

Progression of morphological changes within CNS in a transgenic rat model of familial amyotrophic lateral sclerosis.

UNLABELLED: An analysis of the dynamics of histological and immunocytochemical changes in the CNS of a transgenic rat model of fALS in various periods of life was performed. Material was obtained from animals on the 60th day of age (4), 93rd day of age (3) and 120th presymptomatic day and from 3 animals in paretic stage of the disease. Formalin-fixed and paraffin-embedded slices were stained with HE and Klüver-Barrera method. Immunoreactions to GFAP, S-100, ferritin, neurofilament, ubiquitin, synaptophysin and tau protein were also performed. Within the brain tissues patchy neuronal loss and dark or ischaemic neurons were dispersed in cortical layers, CA1, CA3 and CA4 hippocampal areas and structures of the hemispheres and brain stem. In the spinal cord, numerous alpha motoneurons were dark or ischaemic. Vacuoles or small pale spots were visible in their cytoplasm. Microspongiosis surrounded some motoneurons, particularly cells subjected to neuronophagy. Neuronophagy, sporadically observed at the age of 60th day, was more extensive on the 93rd day of age, and at the age of 120 days already involved all interneurons of the anterior and posterior horns. In the immune reaction to neurofilament numerous fibres, often thick, fragmented or rosary-like, were observed. They were located within subcortical white matter, external and internal capsules, anterior horns of the spinal cord. Changes became more intensive with age. Astrocytic reactivity was weak in animals on the 60th and 93rd day of life. Non-numerous cells were immunoreactive to GFAP and S-100, although an increase of astrocytic nuclei was observed. On the 120th day of age and in symptomatic stage astrocytic hypertrophy and proliferation were intensive. But from the 60th day of age ubiquitin and tau protein immunopositive material was accumulated in the perinuclear area of astroglial cytoplasm. Immunoreaction of nerve cells to these proteins was negative. CONCLUSIONS: 1) In the subclinical stage of the disease the pathological process within the CNS takes place already on the 60th day of age and its intensity increases with age. 2) Morphological changes are not limited to motor neuronal cells. Various structures of the CNS are damaged. 3) Weak astroglial reaction probably depends on pathological accumulation of ubiquitin and tau protein in cytoplasm. 4) Astroglial cells are probably also a "target" for pathogenic factors in the rat model of fALS.

Age Factors↗

PubMed2006

Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS).

Aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS) is still a mystery. Among several hypotheses autoimmune mechanisms are also taken into account. We report here our investigations of auto-antibodies against proteins of spinal cord cells in the cerebrospinal fluid (CSF) and serum of ALS patients. The results were correlated with the severity of disease course. The subjects were 57 ALS patients (29 severe, 28 mild) and 10 normal controls. The major finding in CSF was the presence of antibodies against a 70 kD protein in the majority of ALS patients. This protein was identified as neurofilament 68. The second protein of high reactivity and frequency of appearance was a 82 kD protein, which was identified as a-actinin. Less reactive and less frequent were antibodies directed against 55 kD and 40 kD proteins. They were immunologically defined to be related to desmin and actin, resp. The difference between the reactivity of anti-neurofilament and anti-desmin related protein in the severe and mild ALS groups was significant. More frequent were the anti-neurofilament antibodies in the severe ALS cases as compared to the milder ones. In normal CSF, antibodies directed against 55 kD, 70 kD and 82 kD proteins were present in traces and appeared in 5%, 20% and 10% of cases, respectively. In the serum of 30% of severe ALS patients traces of antibodies against 70 kD protein were detected. The morphological studies in the presence of CSF of ALS patients revealed pronounced immunoreactivity of spinal cord neurons, mainly within anterior horns. The significance of the presence of auto-antibodies in CSF of ALS patients against cellular proteins of the spinal cord is hard to define. It is conceivable that they appear as a secondary immunological consequence of neuronal death. It is also possible that they may accelerate the course of neuronal degeneration.

Actinin↗

PubMed2005

A study of glutathione S-transferase pi expression in central nervous system of subjects with amyotrophic lateral sclerosis using RNA extraction from formalin-fixed, paraffin-embedded material.

The expression of glutathione S-transferase pi (GST pi), an enzyme responsible for inactivation of a large variety of toxic compounds was studied in spinal cord, motor and sensory brain cortex obtained from patients who died in the course of amyotrophic lateral sclerosis (ALS). The studies were performed on formalin-fixed, paraffin-embedded (FFPE) and freshly frozen tissues. The method of RNA isolation from FFPE was modified. A significant decrease of GST pi-mRNA expression was found in cervical spinal cord and motor brain cortex of ALS subjects comparing to analogue control tissues (P<0.01), as well as in motor cortex of ALS subjects comparing to their sensory cortex (P<0.05). In spinal cords the decrease in GST pi-mRNA expression was accompanied by a decrease of GST pi protein level. Results indicated lowered GST pi expression on both mRNA and protein levels in the regions of nervous system affected by ALS. The non-properly inactivated by GST toxic electrophiles and organic peroxides may thus contribute to motor neurons damage.

Adult↗

PubMed2005

Proteinaceous intracellular inclusions in neurodegenerative disorders.

Neurodegenerative disorders are characterized by accumulation of "toxic", pathologic proteins in brain cells. Mutations in genes coding these proteins result in conformational disturbances of the protein structure and their accumulation and aggregation manifesting at the level of light microscope as various intracellular inclusions. This paper is an attempt of approach cellular mechanisms underlying neurodegenerative disorders with special attention to mechanisms of protein elimination.

Animals↗

PubMed2004

CADASIL or CADVaSIL?

In the present study, morphological examination of patients from two unrelated Polish families with CADASIL was performed. Using light microscopy, there were evident changes characteristic to the disease. On electron microscopy, deposits of granular osmiophillic material (GOM) were found not only in cerebral arteries and veins but also in cerebral capillaries and vessels of the internal organs. These findings indicate that pathological process in CADASIL is generalized and involves also small vessels devoid of smooth muscle cells. Therefore, we propose to consider a replacement for the name CADASIL that better reflects the morphological picture of the disease like, for example, cerebral autosomal dominant vasculopathy with subcortical infarcts and leukoencephalopathy (CADVaSIL) or, to preserve the commonly known acronym, cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy.

Adult↗

PubMed2004

CADASIL: what component of the vessel wall is really a target for Notch 3 gene mutations?

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to cognitive decline, dementia and recurrent strokes. The underlying angiopathy of the small vessels is characterized by basophilic degeneration of the media, Notch 3 protein accumulation in vessel wall and a unique type of ultrastructural deposits located nearby the basal lamina. In some cases of CADASIL, morphological changes similar to those observed in panarteritis nodosa (PAN) were found. PAN-like changes manifested as fibrinoid necrosis of the tunica media and perivascular inflammatory infiltrates were found in arteries not only in the central nervous system but also in internal organs. Presence of PAN-like changes indicates that some autoimmunological mechanisms can participate in the CADASIL process. Although vascular smooth muscle cells seem to be a primary target of the pathogenic process triggered by mutations in Notch 3 gene they are probably not the only target. This article gives a brief overview on the morphologic spectrum of the vascular pathological changes in CADASIL and discusses some of the relevant mechanisms that lead from Notch 3 mutations to ischemic infarcts.

Arterioles↗

PubMed2004

Remote morphological changes in the white matter after ischaemic stroke.

Acute phase of stroke is the focus of most experimental and clinical studies on cerebral ischaemia. The scarcity of data on remote changes led us to examine the morphological pictures of brains after ischaemic insults. We paid special attention to the white matter capillaries. We microscopically evaluated 10 brains of patients who died after one month to fourteen years after the ischaemic stroke. Morphological examinations involved the application of routine histological stains and immunohistochemical reactions with antibodies against human albumin, GFAP, macrophage antigen CD 68 and lectins (Ulex europaeus, Wheat Germ agglutinin and Bandeirea simplicifolia). The results showed a swelling of the endothelial cells and their invagination into the vessel lumen. Postapoplectic cavities and white matter spongiosis decreasing with increase in distance from the cavity were observed. Immunohistochemical study showed that there was no segmental immunoreactivity to lectins on the capillary wall. Immune reaction to albumin revealed protein extravasation to the rarefied brain parenchyma. Our results indicate that progressing damage of the white matter after ischaemia may be caused not only by degeneration of axons of neurones destroyed by stroke, but also by pathological changes in small blood vessels, especially in capillaries. Hence, vascular leukoencephalopathy is probably caused by arteriolar damage as well as by microangiopathy.

Aged↗

PubMed2004

Oxidative damage to proteins in the spinal cord in amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which has been linked to the generation of free radicals and oxidative stress. Oxidative damage to spinal cord proteins is suggested to be a contributory factor to neuronal death in ALS. Since proteins are the major targets for free radicals and the so-called "reactive species", therefore the objective of our study was to identify oxidatively damaged spinal cord proteins. The material consisted of spinal cords of 8 sporadic ALS cases and 5 controls. We estimated the level of protein carbonyl moieties, which react quantitatively with 2,4-dinitrophenylhydrazine (DNPH). Afterwards proteins were separated by SDS-polyacrylamide gel electrophoresis and the protein bound DNPH moieties were detected immunochemically. We also morphologically examined spinal cords after immune staining against DNPH. The protein carbonyl content of the ALS spinal cords significantly increased in all examined cases. In most ALS patients, proteins with 125 kDa, 70 kDa and 36kDa were highly oxidized. The 70-kDa protein was identified immunochemically to be neurofilament 68. The morphological examination of ALS spinal cords indicated a pronounced anti-DNPH immune reaction in neurones of the anterior horns; the reaction in the posterior horns was less intense. Microglia in the white matter was immunoreactive; astroglia was DNPH-negative. Although the exact mechanism by which reactive oxygen species induce motor neurones to die is not known yet, the presented data indicate that they affect spinal cord cellular proteins, including neurofilament 68. In this study, we successfully examined the neurochemical features accompanying motor neuron injury in ALS, and the results may help to develop a rationale anti-oxidative neuroprotective strategy.

Aged↗

PubMedDate not supplied

[The role of protein conformational disturbances in the pathomechanism of the extrapyramidal system diseases].

Neurodegenerative disorders are characterised by cell damage due to accumulation of toxic, pathologic proteins. Mutations in genes coding different cell proteins result in conformational disturbances of the protein structure, their accumulation and aggregation manifested at the level of light microscope as various intracellular inclusions. This paper is an attempt of approach to cellular mechanisms underlying neurodegenerative diseases of the extrapyramidal system with special attention to ubiquitin-proteasome pathway -- the pathway whose discoverers received the 2004 Nobel Prize in chemistry.

Animals↗