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.
A fetal, cryopreserved ventral mesencephalic rat tissue was transplanted into striatum of healthy adult rats. A stereotactic apparatus was used for transplantation of solid tissue blocks. The survival of transplanted dopaminergic cells in rat striatum was evaluated by means of histological and immunocytochemical methods (TH - thyrosine hydrolase) 1, 3, 7, 14, and 21 days after transplantation. The cellular reaction of the host to graft and to sham-lesion was examined. Glial fibrillary acidic protein (GFAP) was used for the visualization of astroglial reaction and ferritin for microglia. It was found that fetal cells of cryopreserved rat ventral mesencephalon transplanted into adult rat striatum survive though, in a small number. Cellular reactions of the host to both graft of dopaminergic cells and sham-lesion are similar to glial scar and are nonspecific.
Wilson's disease is a rare, multiorganic genetically coded disorder, induced by impaired copper transport. The recent identification of the disease gene and the discovery of gene product--copper transporting P-type ATPase that is integrate membranous protein has contributed greatly to better understanding of the pathogenesis. This protein is probably essential for incorporation of copper into ceruloplasmin and for its biliary excretion. Multiple mutations of Wilson's disease gene are responsible for the excess of so called "free" copper which is toxic to tissues. Copper toxicity involves first of all, functional disorders of many enzymatic systems, particularly those of respiratory chain enzymes. In the central nervous system, a special kind of copper toxicity is medicated by astroglia, so that a direct, harmful effect of both copper and ammonia on the brain is observed. The authors present a current review on biochemical mechanisms of copper toxicity and physiopathological significance of the CNS astroglia in Wilson's disease.
ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Gugała-Iwaniuk M, Łojek E, Lipczyńska-Łojkowska W, et al. Dynamics of neurocognitive change in patients with mild cognitive impairment. Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii. 2019;28(2):88-98. doi:10.5114/ppn.2019.86253. APA Gugała-Iwaniuk, M., Łojek, E., Lipczyńska-Łojkowska, W., Sawicka, B., Bochyńska, A., & Poniatowska, R. et al. (2019). Dynamics of neurocognitive change in patients with mild cognitive impairment. Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii, 28(2), 88-98. https://doi.org/10.5114/ppn.2019.86253 Chicago Gugała-Iwaniuk, Magdalena, Emilia Łojek, Wanda Lipczyńska-Łojkowska, Beata Sawicka, Anna Bochyńska, Renata Poniatowska, and Waldemar Lechowicz et al. 2019. "Dynamics of neurocognitive change in patients with mild cognitive impairment". Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii 28 (2): 88-98. doi:10.5114/ppn.2019.86253. Harvard Gugała-Iwaniuk, M., Łojek, E., Lipczyńska-Łojkowska, W., Sawicka, B., Bochyńska, A., Poniatowska, R., Lechowicz, W., and Sienkiewicz-Jarosz, H. (2019). Dynamics of neurocognitive change in patients with mild cognitive impairment. Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii, 28(2), pp.88-98. https://doi.org/10.5114/ppn.2019.86253 MLA Gugała-Iwaniuk, Magdalena et al. "Dynamics of neurocognitive change in patients with mild cognitive impairment." Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii, vol. 28, no. 2, 2019, pp. 88-98. doi:10.5114/ppn.2019.86253. Vancouver Gugała-Iwaniuk M, Łojek E, Lipczyńska-Łojkowska W, Sawicka B, Bochyńska A, Poniatowska R et al. Dynamics of neurocognitive change in patients with mild cognitive impairment. Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii. 2019;28(2):88-98. doi:10.5114/ppn.2019.86253.
In the study the influence of giving gammaglobulin on the course of stroke was tested. The trial was double blind, with a control group and with a randomised administering of gammaglobulin and placebo. The condition for including a patient in the trial was clinical diagnosis of stroke, period of time from the onset not longer than five days, and the absence of both clinical and laboratory features of infection. 36 patients were given gammaglobulin (Veinoglobulin Institut Merieux) in 10 g doses at 3-day intervals, 35 patients were given placebo: 10g of albumin. The clinical follow-up lasted 30 days. Three patients from the gammaglobulin group and nine patients from the placebo group died. Administration of gammaglobulin decreased the tisc of death by 74%. The improvement of neurological deficit in 30-day survivals in the treated group was more expressed than in the placebo group. The total number of infections, number of days with increased temperature, number and time of given antibiotics were comparable in both groups. The results obtained suggest that prophylactic treatment with gammaglobulin does not prevent infections but their course is milder with consequent better clinical improvement and lower mortality.
Current views on the pathogenesis of Parkinson's disease are presented. Studies, particularly those carried out during the last decade, highlight the significance of endogenic processes responsible for a cumulative production of neurotoxic substances, especially free oxygen radicals which exert chronic effect on neurons. In Parkinson's disease, overproduction of free radicals and concomitant failure of protective mechanisms are most likely. An excess of free radicals is cytotoxic because of their very high chemical activity and uncontrolled chain reactions with numerous organic compounds, especially those which are mostly responsible for vital functions of cells. Oxidative stress disturbs metabolism of the cell what finally leads to its death most probably due to damage of cell membrane. That results in increased plasma membrane permeability for calcium ions which activate several subcellular mechanisms and initiate the final phase of cell death. Nonprotein-bound "free" iron ions are the strongest and most dangerous generators of free oxygen radicals. It is thought that ferric (Fe-3+" iron bound to neuromelanin may play a profound role in the overproduction of especially cytotoxic hydroxyl radicals, derivatives of molecular oxygen. Both, oxygen stress inducing factor and the sequence of related biochemical disorders remain still unknown. However, the synergy of the excess of reactive oxygen metabolites (mainly free radicals), nitric oxide, "free" iron ions and neuromelanin may contribute considerably to the generation of oxygen stress.
Tobacco smoking during pregnancy is associated with a variety of negative consequences not only for the mother, but also for the developing fetus. Many studies have shown that carcinogens contained in tobacco smoke permeate across the placenta, and are found in fetus. The aim of the study was to determine the prenatal exposure to tobacco-specific carcinogenic N-nitrosamines on the basis of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of smoking and second-hand smoke (SHS) exposed women and in the first urine of their newborns. A questionnaire documenting demographics and socio-economical data, smoking habits and exposure to SHS was completed by 121 delivering women near or at term. Maternal concentrations of cotinine and NNAL were measured in urine of the mother and the first urine of her newborn infant by liquid chromatography tandem mass spectrometry (LC/MS/MS). The mean concentration of cotinine was 439.2 ng/mg creatinine and NNAL concentration in urine of smoking women was 74.0 pg/mg creatinine, and for her newborn 78.6 pg/mg creatinine. Among mothers exposed to SHS, cotinine and NNAL mean concentration were 23.1 ng/mg creatinine, and 26.4 pg/mg creatinine. In newborns of SHS exposed mothers during pregnancy the mean concentration of NNAL was 34.1 pg/mg creatinine, respectively. Active tobacco smoking as well as passive exposure to smoking during pregnancy is an important source of tobacco specific N-nitrosamines to the fetuses as evidenced by increased concentrations of this carcinogen. Determination of NNAL in maternal urine samples can be a useful biomarker of prenatal exposure of newborn to carcinogenic nitrosamines.
A 35-year-old man died after 30 months following the onset of the disease. There was a history of changes in his mental condition, including disturbances of behavior as well as the evidence of progressing dementia. The patient revealed gait disturbances and finally became bed ridden. Bizarre behavior and changes of mood with concurrent growing irritability which predominated during the course of disease, may explain the initial diagnosis of schizophrenia. Then cerebellar and spastic movement disorders leading to paraparesis and sphincters disturbances developed. Clinical symptoms of adrenal failure were not found apart from episodes of arterial pressure fall. After two years a magnetic resonance imaging (MRI) revealed an extensive diffuse demyelinative process in white matter of cerebral and cerebellar hemispheres. Activity of lysosomal enzymes was normal. A general autopsy revealed atrophy of adrenal cortex and the presence of ballooned cells with striated cytoplasm in the reticular and fasciculate zones. Neuropathological examination revealed an extensive demyelination of white matter in cerebral and cerebellar hemispheres and of the long paths of the brain stem, corresponding to changes in MRI examination. Within demyelination areas damage of axons and diffuse cellular and fibrous gliosis were found as well as perivascular lymphocytic infiltrations with the presence of strong PAS (+) and Sudan (+) macrophages. Immunocytochemical reactions with HAM-56 and RCA1 in macrophages were positive. Electron microscopy examination revealed lamellar inclusions in cytoplasm of macrophages. Similar structures were present in the lysosomes of astrocytes. Morphological examination of adrenal glands as well as morphological and ultrastructural study of the brain allowed us to diagnose the cerebral form of adrenoleukodystrophy (ALD). Topography and character of the brain changes seems to be in keeping with a rare schizophrenic-like variant of ALD with progressive dementia. Abnormal plasma profile and increased VLCFA concentration in the patient's 13-year-old daughter confirm the ALD diagnosis.
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.
