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1.
Ticks Tick Borne Dis ; 6(5): 559-67, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25976235

ABSTRACT

Spatial distribution of Ixodes ricinus tick host-seeking activity, as well as prevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV) were studied in the TBE endemic area of South Bohemia (Czech Republic). High variability in tick abundance detected in a network of 30 study sites was most closely associated with characteristics of vegetation cover. Of 11,182 tested tick samples, 12% carried DNA of spirochete from B. burgdorferi s.l. complex. B. afzelii and B. garinii prevailed among spirochete species. The presence of B. spielmanii in the region was confirmed. The median number of borrelial genome copies in positive samples reached 6.6 × 10(3) by real-time PCR. The total prevalence of TBEV in pooled samples reached 0.32% (20,057 samples tested), at least one TBEV positive tick was present in 21 out of 30 sampling sites.


Subject(s)
Borrelia burgdorferi/isolation & purification , Encephalitis Viruses, Tick-Borne/isolation & purification , Ixodes/physiology , Animals , Czech Republic/epidemiology , Encephalitis, Tick-Borne/epidemiology , Encephalitis, Tick-Borne/virology , Female , Lyme Disease/epidemiology , Lyme Disease/microbiology , Male
2.
Klin Khir ; (11-12): 76-8, 2010.
Article in Ukrainian | MEDLINE | ID: mdl-21268804

ABSTRACT

The results of prostaglandin E1 et systemic antibacterial therapy use in 1836 patients, suffering purulent-necrotic affection of foot, were summarized. There was established, that cefuroxym constitutes the first line preparation for the ostheoarthropathy focus elimination, when the affection is limited and the patient state is stable, and meronem--for extended affection and unstable patient's state. In the pronounced ischemia of the foot the initial administration of cefepim is the most effective. For purulent-necrotic affection as a consequence of the foot wounding, erysipelas or operative intervention it is expedient to use carbapenem or meropenem. The systemic antibacterial therapy administration had promoted significant reduction of the treatment duration and improvement of its result.


Subject(s)
Alprostadil/therapeutic use , Anti-Bacterial Agents/therapeutic use , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetic Foot/drug therapy , Adult , Aged , Aged, 80 and over , Alprostadil/administration & dosage , Anti-Bacterial Agents/administration & dosage , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/microbiology , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/surgery , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/microbiology , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/surgery , Diabetic Foot/etiology , Diabetic Foot/microbiology , Diabetic Foot/pathology , Diabetic Foot/surgery , Drug Therapy, Combination , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Necrosis , Treatment Outcome , Young Adult
3.
Histol Histopathol ; 23(12): 1477-83, 2008 12.
Article in English | MEDLINE | ID: mdl-18830933

ABSTRACT

Previous studies have described elevated lipid peroxidase, myeloperoxidase and xanthine oxidoreductase/xanthine oxidase levels on the ocular surface of patients suffering from autoimmune dry eye (Sjögren's syndrome, SS). Reactive oxygen species generated by various enzymatic systems may be dangerous to the eye if they are not sufficiently cleaved by antioxidants. Because antioxidants have not been investigated in dry eye, the aim of this study was to examine the expression of antioxidant enzymes that cleave reactive oxygen species and play a key role in antioxidant protection. Conjunctival epithelial cells of dry eye (SS) patients were obtained by the method of impression cytology using Millicell membranes. Normal eyes served as controls. In the conjunctival epithelium superoxide dismutase, catalase and glutathione peroxidase were examined immunohistochemically. The enzyme expression levels were determined by image analysis and statistical evaluation. In contrast to normal eyes, where antioxidant enzymes were highly expressed in the conjunctival epithelium, in dry eye their expression was much less pronounced in correlation with the increasing severity of dry eye symptoms. Our study suggests that the decreased expression of antioxidant enzymes in dry eye disease (SS) contributes to the development of anterior eye surface oxidative injuries.


Subject(s)
Antioxidants/metabolism , Catalase/biosynthesis , Conjunctiva/enzymology , Glutathione Peroxidase/biosynthesis , Sjogren's Syndrome/enzymology , Superoxide Dismutase/biosynthesis , Epithelium/enzymology , Female , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Male , Middle Aged , Oxidative Stress/physiology
4.
Nitric Oxide ; 17(1): 10-7, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17600738

ABSTRACT

Until now, the expression and possible role of nitric oxide and nitrogen related oxidants in the human dry eye have not been investigated. Therefore, we examined immunohistochemically nitric oxide synthase isomers (NOS), enzymes generated nitric oxide, nitrotyrosine, a cytotoxic byproduct of nitric oxide and malondialdehyde, a byproduct of lipid peroxidation, in conjunctival epithelium of patients with dry eye, Sjögren's syndrome (SS). Moreover, in conjunctival epithelium of patients with dry eye (SS) the immunohistochemical staining of some pro-inflammatory cytokines was demonstrated: mature interleukin-1 beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha). Conjunctival epithelial cells were obtained by the method of impression cytology. Normal eyes served as controls. In contrast to the normal eyes where endothelial nitric oxide synthase (NOS3) as well as inducible nitric oxide synthase (NOS2) were only slightly expressed in conjunctival epithelium, in dry eye both NOS (mainly NOS2) were gradually expressed along the severity of dry eye symptoms which was in accord with pro-inflammatory cytokine immunodetection (IL-1beta, IL-6, IL-8, TNF-alpha) in dry eye conjunctival cytology samples. This was in contrast to normal eyes where the staining of pro-inflammatory cytokines was weak or completely absent. Peroxynitrite formation (demonstrated by nitrotyrosine residues) and lipid peroxidation (evaluated by increased malondialdehyde staining) were also found in conjunctival epithelium of dry eye with highly pronounced symptoms of dryness. In conclusion, results point to the suggestion that reactive nitrogen species are involved in the pathogenesis or self-propagation of autoimmune dry eye (SS).


Subject(s)
Conjunctiva/metabolism , Epithelium/metabolism , Nitric Oxide Synthase/metabolism , Nitrogen/metabolism , Oxidants/metabolism , Sjogren's Syndrome/metabolism , Adult , Conjunctiva/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Models, Biological , Nitric Oxide/metabolism , Tumor Necrosis Factor-alpha/metabolism
5.
Histol Histopathol ; 22(9): 997-1003, 2007 09.
Article in English | MEDLINE | ID: mdl-17523077

ABSTRACT

Previous papers examined lipid peroxidase levels and myeloperoxidase activity as products of oxidative and inflammatory reactions in the tear fluid of patients suffering from dry eye. The aim of the present paper was to investigate whether the enzymes xanthine oxidoreductase/xanthine oxidase known to generate reactive oxygen species contribute to oxidative reactions on the ocular surface. Xanthine oxidoreductase/xanthine oxidase were examined immunohistochemically as well as histochemically in conjunctival epithelial cells of patients suffering from dry eye. Patients with verified autoimmune dry eye (Sjögren's syndrome) participated in our study; normal eyes served as controls. Conjunctival epithelial cells were obtained by the method of impression cytology using Millicell membranes. The results revealed a pronounced expression, as well as activity of xanthine oxidoreductase/xanthine oxidase in the conjunctival epithelium of dry eye. It is suggested that reactive oxygen species which are generated by this enzymatic system, contribute to oxidative reactions on the eye surface of patients with ocular manifestations of autoimmune disease (Sjögren's syndrome).


Subject(s)
Conjunctiva/metabolism , Dry Eye Syndromes/metabolism , Epithelial Cells/enzymology , Sjogren's Syndrome/metabolism , Xanthine Oxidase/metabolism , Adult , Conjunctiva/cytology , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/pathology , Epithelial Cells/metabolism , Female , Fluorescein , Fluorescent Dyes , Histocytochemistry , Humans , Immunohistochemistry , Male , Middle Aged , Oxidation-Reduction , Severity of Illness Index , Sjogren's Syndrome/complications , Sjogren's Syndrome/pathology , Tears/metabolism
6.
Prague Med Rep ; 107(1): 71-80, 2006.
Article in English | MEDLINE | ID: mdl-16752805

ABSTRACT

Cell migration in the adult brain is discussed. We compared our studies on cell densities after cortical injury with our study on hippocampal proliferation and neurogenesis. We have shown that postnatal hypoxia increases cell density in cortical layer II of the somatosensory, motor and auditory cortices and in layer V of the motor cortex. Moreover, we have shown that a photochemical lesion through the entire cortical thickness increases the number of newly generated cells. The number of newly generated cells was enhanced by beam walking pre-treatment and substantially enhanced by fluoxetine pre-treatment; following fluoxetine pre-treatment, a large number of newly generated cells were observed in the auditory cortex. Subsequently, we studied the generation of new cells in the hippocampal dentate gyrus. After Morris water maze training, in comparison with an untrained group, proliferation in the granular cell layer was suppressed. That suppression was compensated for by fluoxetine administration during the period of learning. We observed different results in the hilus of the dentate gyrus, where suppression was observed after combined Morris water maze and fluoxetine treatment. We hypothesize that cell migration in the brain cortex persists in adulthood and that this migration is stimulated by both physiological and pathological conditions. Appropriate stimulation of the neurogenetic system is a possible promising therapy for brain diseases.


Subject(s)
Cell Movement , Cerebral Cortex/cytology , Cerebral Cortex/embryology , Aging , Animals , Cell Differentiation , Cell Movement/drug effects , Cell Proliferation , Fluoxetine/pharmacology , Hypoxia, Brain/pathology , Rats , Stress, Physiological/pathology
7.
Hippocampus ; 12(2): 269-79, 2002.
Article in English | MEDLINE | ID: mdl-12000123

ABSTRACT

The extracellular space (ECS) is the microenvironment of the nerve cells and an important communication channel, allowing for long-distance extrasynaptic communication between cells. Changes in ECS size, geometry, and composition have been reported in diverse (patho)physiological states, including aging. In the present study, real-time tetramethylammonium (TMA+) iontophoresis was used to quantify ECS diffusion parameters in different brain regions of adult and behaviorally characterized aged rats. Prior to ECS diffusion measurement, superior and inferior learners were selected from a large group of aged rats, according to their performance in the open-field water maze. The main finding was that the degree of impaired maze performance of old rats correlates, firstly, with decrease in ECS volume, loss of diffusion anisotropy in hippocampus, and degree of astrogliosis, and secondly, with disorganization of the astrocytic processes and reduction of hippocampal ECS matrix molecules. Importantly, no significant differences were found in the density of neurons in any region of the hippocampus or dentate gyrus. The alterations in hippocampal diffusion parameters evident in aged animals with severe learning deficits could account for the learning impairment, due to their effects on extrasynaptic volume transmission and/or on the "cross-talk" between synapses, which has been suggested to be involved in neural processes associated with learning and memory formation.


Subject(s)
Aging/metabolism , Aging/pathology , Extracellular Space/metabolism , Hippocampus/metabolism , Hippocampus/pathology , Maze Learning/physiology , Animals , Anisotropy , Astrocytes/chemistry , Astrocytes/cytology , Astrocytes/metabolism , Cell Count , Diffusion , Fibronectins/analysis , Glial Fibrillary Acidic Protein/analysis , Gliosis/metabolism , Gliosis/pathology , Glycoproteins/metabolism , Immunohistochemistry , Iontophoresis , Neurons/chemistry , Neurons/cytology , Neurons/metabolism , Rats , Rats, Wistar
8.
Klin Khir ; (8): 42-7, 2001 Aug.
Article in Ukrainian | MEDLINE | ID: mdl-11794111

ABSTRACT

Efficacy of antibacterial therapy was analyzed in 266 patients with diabetes mellitus and purulent-necrotic affection of the foot. In presence of affection of bones and joints good effect was achieved while conduction of antibacterial therapy and in the cases of open wound--while local administration of systemic antibacterial preparations.


Subject(s)
Anti-Infective Agents/therapeutic use , Diabetic Foot , Adult , Aged , Aged, 80 and over , Anti-Infective Agents/administration & dosage , Diabetic Foot/drug therapy , Diabetic Foot/microbiology , Diabetic Foot/pathology , Female , Humans , Male , Middle Aged , Necrosis , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Severity of Illness Index
9.
Tissue Eng ; 5(5): 467-88, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10586102

ABSTRACT

A biocompatible heterogeneous hydrogel of poly [N-(2-hydroxypropyl) methacrylamide] (PHPMA), was evaluated for its ability to promote tissue repair and enhance axonal regrowth across lesion cavities in the brain and spinal cord in adult and juvenile (P17 P21) rats. Incorporation of PHPMA hydrogels into surrounding host tissue was examined at the ultrastructural level and using immunohistochemical techniques. In addition, and in parallel to these studies, diffusion parameters (volume fraction and tortuosity of the gel network) of the PHPMA hydrogels were evaluated pre- to postimplantation using an in vivo real-time iontophoretic method. The polymer hydrogels were able to bridge tissue defects created in the brain or spinal cord, and supported cellular ingrowth, angiogenesis, and axonogenesis within the structure of the polymer network. As a result, a reparative tissue grew within the porous structure of the gel, composed of glial cells, blood vessels, axons and dendrites, and extracellular biological matrices, such as laminin and/or collagen. Consistent with matrix deposition and tissue formation within the porous structure of the PHPMA hydrogels, there were measurable changes in the diffusion characteristics of the polymers. Extracellular space volume decreased and tortuosity increased within implanted hydrogels, attaining values similar to that seen in developing neural tissue. PHPMA polymer hydrogel matrices thus show neuroinductive and neuroconductive properties. They have the potential to repair tissue defects in the central nervous system by replacing lost tissue and by promoting the formation of a histotypic tissue matrix that facilitates and supports regenerative axonal growth. () ()


Subject(s)
Brain Injuries/drug therapy , Nerve Regeneration/drug effects , Polymethacrylic Acids/therapeutic use , Spinal Cord Injuries/therapy , Wound Healing/drug effects , Animals , Axons/ultrastructure , Biocompatible Materials , Brain Injuries/pathology , Dendrites/ultrastructure , Diffusion , Extracellular Matrix/physiology , Female , Frontal Lobe/injuries , Frontal Lobe/ultrastructure , Hydrogels/chemistry , Microscopy, Electron , Neovascularization, Physiologic/drug effects , Neuroglia/ultrastructure , Polymethacrylic Acids/administration & dosage , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/pharmacology , Porosity , Rats , Rats, Sprague-Dawley , Rats, Wistar , Spinal Cord Injuries/pathology
10.
Neuroscience ; 91(2): 783-98, 1999.
Article in English | MEDLINE | ID: mdl-10366034

ABSTRACT

Fetal neocortex or tectum transplanted to the midbrain or cortex of newborn rats develops various degrees of gliosis, i.e. increased numbers of hypertrophied, glial fibrillary acidic protein-positive astrocytes. In addition, there were patches or bundles of myelinated fibres positive for the oligodendrocyte and central myelin marker Rip, and increased levels of extracellular matrix molecules. Three diffusion parameters--extracellular space volume fraction alpha (alpha = extracellular volume/total tissue volume), tortuosity lambda (lambda = square root(D/ADC), where D is the free and ADC is the apparent tetramethylammonium diffusion coefficient) and non-specific uptake k'--were determined in vivo from extracellular concentration-time profiles of tetramethylammonium. Grafts were subsequently processed immunohistochemically to compare diffusion measurements with graft morphology. Comparisons were made between the diffusion parameters of host cortex and corpus callosum, fetal cortical or tectal tissue transplanted to host midbrain ("C- and T-grafts") and fetal cortical tissue transplanted to host cortex ("cortex-to-cortex" or C-C-grafts). In host cortex, alpha ranged from 0.20 +/- 0.01 (layer V) to 0.21 +/- 0.01 (layers III, IV and VI) and lambda from 1.59 +/- 0.03 (layer VI) to 1.64 +/- 0.02 (layer III) (mean +/- S.E.M., n = 15). Much higher values were found in "young" C-grafts (81-150 days post-transplantation), where alpha = 0.34 +/- 0.01 and lambda = 1.78 +/- 0.03 (n = 13), as well as in T-grafts, where alpha = 0.29 +/- 0.02 and lambda = 1.85 +/- 0.04 (n = 7). Further analysis revealed that diffusion in grafts was anisotropic and more hindered than in host cortex. The heterogeneity of diffusion parameters correlated with the structural heterogeneity of the neuropil, with the highest values of alpha in gray matter and the highest values of lambda in white matter bundles. Compared to "young" C-grafts, in "old" C-grafts (one year post-transplantation) both alpha and lambda were significantly lower, and there was a clear decrease in glial fibrillary acidic protein immunoreactivity throughout the grafted tissue. In C-C-grafts, alpha and lambda varied with the degree of graft incorporation into host tissue, but on average they were significantly lower (alpha = 0.24 +/- 0.01 and lambda = 1.66 +/- 0.02, n = 8) than in young C- and T-grafts. Well-incorporated grafts revealed less astrogliosis, and alpha and lambda values were not significantly higher than those in normal host cortex. The observed changes in extracellular space diffusion parameters could affect the movement and accumulation of neuroactive substances and thus impact upon neuron-glia communication, synaptic and extrasynaptic transmission in the grafts. The potential relevance of these observations to human neuropathological conditions associated with acute or chronic astrogliosis is considered.


Subject(s)
Astrocytes/cytology , Brain Tissue Transplantation/physiology , Fetal Tissue Transplantation/physiology , Neocortex/transplantation , Oligodendroglia/cytology , Superior Colliculi/transplantation , Animals , Animals, Newborn , Astrocytes/physiology , Cell Size , Cerebral Cortex/cytology , Cerebral Cortex/physiology , Embryo, Mammalian , Extracellular Space/physiology , Gestational Age , Humans , Mesencephalon/cytology , Mesencephalon/physiology , Neocortex/cytology , Neocortex/physiology , Oligodendroglia/physiology , Rats , Superior Colliculi/cytology , Superior Colliculi/physiology
11.
Glia ; 25(1): 56-70, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9888298

ABSTRACT

Cell swelling and astrogliosis (manifested as an increase in GFAP) were evoked in isolated rat spinal cords of 4-21-day-old rats by incubation in either 50 mM K+ or hypotonic solution (235 mosmol kg(-1)). Application of K+ and hypotonic solution resulted at first in a decrease of extracellular space (ECS) volume fraction alpha (ECS volume/total tissue volume) and an increase in tortuosity lambda (lambda2 = free/apparent diffusion coefficient) in spinal gray (GM) and white matter (WM). These changes resulted from cell swelling, since the total water content (TW) in spinal cord was unchanged and the changes were blocked in Cl- -free solution and slowed down by furosemide and bumetanide. Diffusion in WM was anisotropic, i.e., more facilitated along fibers (x-axis) than across them (y- or z-axis). The increase of lambda(y,z) was greater than that of lambda(x), reaching unusually high values above 2.4. In GM only, during continuous 45 min application, alpha and lambda started to return towards control values, apparently due to cell shrinkage of previously swollen cells since TW remained unchanged. This return was blocked by fluoroacetate, suggesting that most of the changes were due to the swelling of glia. A 45 min application of 50 mM K+ and, to a lesser degree, of hypotonic solution evoked astrogliosis, which persisted after washing out these solutions with physiological saline. During astrogliosis lambda increased again to values as high as 2.0, while alpha either returned to or increased above control values. This persistent increase in lambda after washout was also found in WM, and, in addition, the typical diffusion anisotropy was diminished. Our data show that glial swelling and astrogliosis are associated with a persistent increase in ECS diffusion barriers. This could lead to the impairment of the diffusion of neuroactive substances, extrasynaptic transmission, "crosstalk" between synapses and neuron-glia communication.


Subject(s)
Astrocytes/physiology , Neuroglia/physiology , Spinal Cord/cytology , Animals , Astrocytes/ultrastructure , Body Water/metabolism , Cell Size , Diffusion , Hypotonic Solutions , Immunohistochemistry , Neuroglia/ultrastructure , Neuronal Plasticity/physiology , Oligodendroglia/physiology , Oligodendroglia/ultrastructure , Potassium/pharmacology , Rats , Rats, Wistar , Spinal Cord/metabolism , Spinal Cord/ultrastructure , Synaptic Transmission
12.
Neuroreport ; 9(7): 1299-304, 1998 May 11.
Article in English | MEDLINE | ID: mdl-9631417

ABSTRACT

We provide evidence for anisotropic diffusion in rat corpus callosum and hippocampus. The preferential diffusion pathway in corpus callosum is along the myelinated axon fibres; in the hippocampus diffusion is easier along the transversal axis (x) than along the sagittal (y) or vertical (z) axes. In all areas studied, i.e. in the cortex, corpus callosum and hippocampus, the mean ECS volume fraction alpha (alpha = ECS volume/total tissue volume) ranged between 0.20 and 0.22 and mean non-specific uptake k' was between 4.0 and 5.9 x 10(-3) s-1. Diffusional anisotropy in the hippocampus may be of importance for extrasynaptic transmission and in the 'cross-talk' between synapses.


Subject(s)
Corpus Callosum/physiology , Hippocampus/physiology , Animals , Anisotropy , Axons/physiology , Diffusion , Extracellular Space/physiology , Iontophoresis/instrumentation , Iontophoresis/methods , Male , Nerve Fibers/physiology , Pyramidal Cells/physiology , Quaternary Ammonium Compounds/pharmacokinetics , Rats , Rats, Wistar
13.
Exp Gerontol ; 33(7-8): 837-51, 1998.
Article in English | MEDLINE | ID: mdl-9951627

ABSTRACT

Changes in brain extracellular space (ECS) volume, composition, and geometry are a consequence of neuronal activity, of glial K+, pH, and amino acid homeostasis, and of changes in glial cell morphology, proliferation, and function. They occur as a result of repetitive neuronal activity, seizures, anoxia, injury, inflammation, and many other pathological states in the CNS, and may significantly affect signal transmission in the CNS. Activity-related or CNS damage-related cellular swelling is compensated for by ECS volume shrinkage and, as a consequence, by a decrease in the apparent diffusion coefficients (ADCs) of neuroactive substances diffusing in the ECS. Changes in cellular morphology, such as occur during aging, could also result in changes of ECS volume and geometry. We provide evidence for limited diffusion in rat cortex, corpus callosum, and hippocampus in the aging brain that correlates with changes in glial volume and the extracellular matrix. In all structures, the mean ECS volume fraction alpha (alpha = ECS volume/total tissue volume) and nonspecific uptake k' are significantly lower in aged rats (26-32 months old) than in young adult brain. Compared to young adult brain, in the aged brain we found an increase in GFAP staining and hypertrophied astrocytes with thicker processes which, in the hippocampus, lost their radial organization. The tortuosity (lambda = square root of D/ADC) was lower in the cortex and CA3 region. Immunohistochemical staining for fibronectin and chondroitin sulfate proteoglycans revealed a substantial decrease that could account for a decrease in diffusion barriers. Diffusion parameters alpha, lambda, and k' in the aging brain after cardiac arrest changed substantially faster than in the young adult brain, although the final values were not significantly different. This suggests that the smaller extracellular space during aging results in a greater susceptibility of the aging brain to anoxia/ischemia, apparently due to a faster extracellular acidosis and accumulation of K+ and toxic substances, for example, glutamate. We conclude that during aging the movement of substances is more hindered in the narrower clefts. This is partly compensated for by a decrease in the diffusion barriers that may be formed by macromolecules of the extracellular matrix. Diffusion parameters can affect the efficacy of synaptic as well as extrasynaptic transmission by a greater accumulation of substances, because they diffuse away from a source more slowly, or induce damage to nerve cells if these substances reach toxic concentrations. Diffusion parameters are also of importance in the "crosstalk" between synapses, which has been hypothesized to be of importance during LTP and LTD. We can, therefore, assume that the observed changes in ECS diffusion parameters during aging can contribute to functional deficits and memory loss.


Subject(s)
Aging/physiology , Brain/physiology , Cell Communication/physiology , Neuroglia/physiology , Neurons/physiology , Animals , Brain/cytology , Brain/metabolism , Brain/pathology , Brain Ischemia/metabolism , Brain Ischemia/pathology , Diffusion , Extracellular Space/metabolism , Female , Male , Rats , Rats, Wistar
14.
Neuroscience ; 70(2): 597-612, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8848163

ABSTRACT

Three diffusion parameters of brain tissue, extracellular space volume fraction (alpha), tortuosity (lambda) and non-specific uptake (kappa') of tetramethylammonium were studied in the somatosensory neocortex and subcortical white matter of the rat during postnatal development (postnatal days 2-21) after X-irradiation at postnatal days 0-1. The diffusion parameters were determined from extracellular concentration-time profiles of tetramethylammonium. The tetramethylammonium concentration was measured in vivo with ion-selective microelectrodes positioned 130-200 microns from an iontophoretic source. X-irradiation with a single dose of 40 Gy resulted in typical early morphological changes in the tissue, namely cell death, DNA fragmentation, extensive neuronal loss, blood-brain barrier damage, activated macrophages, astrogliosis, increase in extracellular fibronectin and concomitant changes in all three diffusion parameters. The changes were observed as early as 48 h post-irradiation (at postnatal days 2-3) and still persisted at postnatal day 21. On the other hand, X-irradiation with a single dose of 20 Gy resulted in relatively light neuronal damage and loss, while blood-brain barrier damage, astrogliosis and changes in diffusion parameters were not significantly different from those found with 40 Gy. It is known that the volume fraction of the extracellular space in the non-irradiated cortex is large in newborn rats and diminishes with age [Lehmenkühler A. et al. (1993) Neuroscience 55, 339-351]. X-irradiation with a single dose of 40 or 20 Gy blocked the normal pattern of volume fraction decrease during postnatal development, and in fact brought about a significant increase. At postnatal days 4-5, alpha increased to 0.49 +/- 0.036 in layer III, 0.51 +/- 0.042 in layer IV, 0.48 +/- 0.02 in layer V, 0.48 +/- 0.028 in layer VI and 0.48 +/- 0.025 in the white matter. The large increase in alpha persisted three weeks after X-irradiation. Tortuosity and non-specific uptake decreased significantly at postnatal days 2-5; at days 8-9 they were not significantly different from those of control animals, while they increased significantly at days 10-21. Less pronounced but significant changes in all three diffusion parameters were also found in areas in the ipsilateral hemisphere adjacent to directly X-irradiated cortex. Compared to the control animals [Lehmenkühler A. et al. (1993) Neuroscience 55, 339-351], a significant decrease of alpha, lambda and kappa' was found in the contralateral hemisphere 48-72 h after X-irradiation. Later, alpha values were not significantly different from those in control animals. The decrease in lambda persisted at postnatal days 4-5. A significant increase in lambda and kappa' was found at postnatal days 18-21. We conclude that X-irradiation of the brain in the early postnatal period, even when it results in only relatively light damage, still produces changes in all three diffusion parameters, particularly a large increase in extracellular space volume fraction in all cortical layers, and in the subcortical white matter. Such changes in extracellular volume fraction of the brain can contribute to impairment of signal transmission, e.g. by diluting ions and neuroactive substances released from cells, and can play an important role in functional deficits, as well as in the impairment of developmental processes. Moreover, the increase in tortuosity (inferred from the decrease in apparent diffusion coefficient) in the X-irradiated cortex, as well as in the contralateral hemisphere, suggests that, even when extracellular volume is large, the diffusion of the substances is substantially hindered.


Subject(s)
Brain/radiation effects , Extracellular Space/radiation effects , Animals , Animals, Newborn , Immunohistochemistry , Rats , Rats, Wistar
15.
Physiol Res ; 45(1): 11-22, 1996.
Article in English | MEDLINE | ID: mdl-8884919

ABSTRACT

Three diffusion parameters of nervous tissue, extracellular space (ECS) volume fraction (alpha), tortuosity (gamma) and non-specific uptake (k') of tetramethylammonium (TMA+), were studied in the spinal cord of rats during experimental autoimmune encephalomyelitis (EAE). The three parameters were determined in vivo from concentration-time profiles of TMA+ using ion-selective microelectrodes. EAE was induced by injection of guinea-pig myelin basic protein (MBP), which resulted in typical morphological changes in the CNS tissue, namely inflammatory reaction, astrogliosis, blood-brain barrier (BBB) damage and paralysis. EAE was accompanied by a statistically significant increase of alpha (mean +/- S.E.M.) in the dorsal horn from 0.21 +/- 0.01 to 0.28 +/- 0.02, in the intermediate region from 0.22 +/- 0.01 to 0.33 +/- 0.02, in the ventral horn from 0.23 +/- 0.01 to 0.47 +/- 0.02 and in white matter from 0.18 +/- 0.03 to 0.30 +/- 0.03. There were significant decreases in tortuosity in the dorsal horn and in the intermediate region and decreases in non-specific uptake in the intermediate region and in the ventral horn. Although the inflammatory reaction and the astrogliosis preceded and greatly outlasted the neurological symptoms, the BBB damage had a similar time course. Moreover, there was a close correlation between the changes in extracellular space diffusion parameters and the manifestation of neurological signs. We suggest that the expansion of the extracellular space alters the diffusion properties in the spinal cord. This may affect synaptic as well as non-synaptic transmission, intercellular communication and recovery from acute EAE, and may contribute to the manifestation of neurological signs in EAE rats.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/pathology , Extracellular Space/physiology , Spinal Cord/pathology , Animals , Blood-Brain Barrier/physiology , Diffusion , Electrophysiology , Female , Gliosis/pathology , Immunohistochemistry , Iontophoresis , Male , Microelectrodes , Paralysis/physiopathology , Quaternary Ammonium Compounds/metabolism , Rats , Rats, Inbred Lew
16.
Brain Res ; 594(1): 19-30, 1992 Oct 23.
Article in English | MEDLINE | ID: mdl-1467938

ABSTRACT

Activity-related transient changes in extracellular K+ concentration ([K+]e) and pH (pHe) were studied by means of ion-selective microelectrodes in neonatal rat spinal cords isolated from pups 2-14 days of age. Pups 1 to 2 days old were X-irradiated to impair gliogenesis and spinal cords were isolated 2-13 days postirradiation (PI). In 2- to 14-day-old pups PI stimulation produced ionic changes that were the same as those in 3- to 6-day-old control (non-irradiated) pups; e.g. the [K+]e increased by 4.03 +/- 0.24 mM (mean +/- S.E.M., n = 30) at a stimulation frequency of 10 Hz and this was accompanied by an alkaline shift of 0.048 +/- 0.004 pH units (mean +/- S.E.M., n = 32) pH units. By contrast, stimulation in non-irradiated 10- to 14-day-old pups produced smaller [K+]e changes, of 1.95 +/- 0.12 mM (mean +/- S.E.M., n = 30), and an acid shift of 0.035 +/- 0.003 pH units which was usually preceded by a scarcely discernible initial alkaline shift, as is also the case in adult rats. Our results show that the decrease in [K+]e ceiling level and the development of the acid shift in pHe are blocked by X-irradiation. Concomitantly, typical continuous development of GFAP-positive reaction was disrupted and densely stained astrocytes in gray matter of 10- to 14-day-old pups PI revealed astrogliosis. In control 3- to 6-day-old pups and in pups PI the stimulation-evoked alkaline, but not the acid, shift was blocked by Mg2+ and picrotoxin (10(-6) M). The acid shift was blocked, and the alkaline shift enhanced, by acetazolamide, Ba2+, amiloride and SITS. Application of GABA evoked an alkaline shift in the pHe baseline which was blocked by picrotoxin and in HEPES-buffered solution. By contrast, the stimulus-evoked alkaline shifts were enhanced in HEPES-buffered solutions. The results suggest a dual mechanism of the stimulus-evoked alkaline shifts. Firstly, the activation of GABA-gated anion (Cl-) channels induces a passive net efflux of bicarbonate, which may lead to a fall in neuronal intracellular pH and to a rise in the pHe. Secondly, bicarbonate independent alkaline shifts may arise from synaptic activity resulting in a flux of acid equivalents.


Subject(s)
Animals, Newborn/metabolism , Astrocytes/radiation effects , Neuroglia/radiation effects , Potassium/metabolism , Spinal Cord/radiation effects , Animals , Animals, Newborn/growth & development , Astrocytes/metabolism , Electric Stimulation , Homeostasis/radiation effects , Hydrogen-Ion Concentration , Immunoenzyme Techniques , Ion Transport/drug effects , Neuroglia/metabolism , Rats , Spinal Cord/growth & development , Spinal Cord/metabolism , X-Rays
18.
Radiobiologiia ; 31(1): 137-9, 1991.
Article in Russian | MEDLINE | ID: mdl-2008513

ABSTRACT

In lymphocytes of sheep exposed to 52 and 103 mC/kg radiation revealed was an increase in spontaneous incorporation of 3H-thymidine into DNA. A change in spontaneous DNA-synthesizing activity in lymphocytes of exposed animals was accompanied by the increase in the total protein content of the peripheral blood lymphocytes.


Subject(s)
DNA/radiation effects , Lymphocytes/radiation effects , Animals , Blood Proteins/metabolism , Blood Proteins/radiation effects , Cell Survival/radiation effects , DNA/biosynthesis , DNA/blood , Dose-Response Relationship, Radiation , Gamma Rays , Lymphocytes/metabolism , Sheep , Thymidine/blood , Tritium
19.
Ortop Travmatol Protez ; (10): 40-4, 1989 Oct.
Article in Russian | MEDLINE | ID: mdl-2622635

ABSTRACT

The authors evaluate the results of 90 decompression operations in 68 patients with Perthes' disease at stages I-IV; the mean age of the children was 8.3 +/- 1.2 years and the follow-up period after the surgery was from 6 months to 10 years. Decompression operations made in the clinic have been protected by author's certificates No. 942712 and No. 1050672. The results were excellent and good in 87.8% and satisfactory in 12.2%. Decompression operations are substantiated from the pathogenetic viewpoint. They interrupt the pathologic process in the epiphysis, contribute to a rapid restoration of the femoral head, are characterized by low traumatism and may be performed simultaneously on both sides which precipitate the children's rehabilitation. The best results have been observed in the children aged 5 to 7 years and at stages I and II of the disease. The surgical treatment has allowed to reduce the terms of the treatment of the children 3 to 4-fold as compared with the conservative method.


Subject(s)
Bone Transplantation/methods , Femur Head Necrosis/surgery , Femur Head/surgery , Hip Joint/surgery , Legg-Calve-Perthes Disease/surgery , Adolescent , Age Factors , Biomechanical Phenomena , Child , Child, Preschool , Hip Joint/physiopathology , Humans , Legg-Calve-Perthes Disease/physiopathology , Legg-Calve-Perthes Disease/rehabilitation
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