The study was performed on cerebral tissue resected during temporal lobectomy in 16 patients whose long-standing cryptogenic epilepsy did not submit to anticonvulsive drugs. Cases presenting definite etiological factors such as CNS trauma, infection or neoplasm were excluded. Neuropathological investigations disclosed microangiomas and focal vascular malformations in the meninges and tissue in 7 patients. Neuronal heterotopias in the white matter and of the white matter in the cortex were observed in 3 cases, Main cortical changes were: neuronal loss,chronic neuronal degeneration, perineuronal satellitosis, and GFAP-positive submeningeal gliosis, especially at the bottom of sulci, perivascular gliosis and laminar or diffuse gliosis. the changes in the hippocamus were most enhanced in the end-plate and in the sector H3 of the pyramidal layer. Astrocytic gliosis in the white matter presented distinct GFAP and S-100 immunostaining; the latter involved in some cases a wider area than the GFAP reaction. The above named changes are analysed with regard to the presumed epileptogenic factors and to the postepileptic damage.
determined the sensitivity of neurons and neuroblastoma cells on apoptosis and necrosis induction upon quercetin treatment. No expression of Hsp72 was observed in neurons, which were more sensitive to cell death upon quercetin treatment than neuroblastoma cells, where Hsp72 expression was observed. Reduction of Hsp72 gene expression in neuroblastoma cells by antisense oligonucleotides made them more sensitive to pro-apoptotic action of quercetin. Moreover, the flavonoid decreased Hsp27, procaspase-3, MRP and PKB expression in neuroblastoma cells and in neurons. Nuclear localization of mainly cytoplasmic Hsp27 was observed in neuroblastoma cells after treatment with high quercetin concentrations, while in neurons, the protein was present in nuclei both in control and quercetin treated cells. Our results suggest that quercetin induce apoptosis more effectively in cells with low level of Hsp 72 expression. Higher sensitivity of neurons for cell death after treatment with high quercetin concentrations in comparison to neuroblastoma cell line should also be taken into consideration in further studies on using studied flavonoid as therapeutic agent.
Quercetin, one of the major flavonoids, exhibits many beneficial effects on human organism as antihistamine, antioxidant, anti-inflammatory, anticancer and antiviral drug. It is recommended as suplement of healthy diet but still the knowledge of its beneficial effect on normal cells is not satisfactory. We decided to examine the effect of flavonoid on neurons morphology and their susceptibility to cell death. Fractal analysis of rat neurons revealed that 24 hours long incubation with quercetin diminished neuronal arborisation in cortical neurons. Neurons also appeared to be very sensitive to cell death after flavonoid treatment in concentration dependent manner. Over 50% of cells died after incubation with 15 ?g/ml of flavonoid while 1 ?g/ ml of quercetin induced cell death only in 5%. Staining with Hoechst 33342 and propidium ioidide revealed the two types of cell death: apoptosis and necrosis. The number of apoptotic cells was comparable with necrotic ones. These results suggest toxic effect of quercetin on neurons what should be taken into consideration in further studies on using quercetin as therapeutic agent.
Astrocytes are the main class of neuroglia, serving a wide range of adaptive functions in the mammalian nervous system. They interact with neurons, providing structural, metabolic and trophic support for them. In pathological circumstances, astrocytes have the potential to induce neuronal dysfunction, but they can also play a neuroprotective role, releasing neuronal growth factors. Here we review recent findings regarding the role of astrocytes in the biology of the brain in physiological conditions, as well as their reaction following the onset of neurodegenerative disorders.
Neurons in the trigeminal sensory nuclei (TSN) were indicated to project simultaneously to the cerebellar paramedian lobule (PML) of both sides by way of axon collaterals in the rabbit. Injections of Fast Blue and Diamidino Yellow made in twelve rabbits into the regions of the left and right PML cortex, respectively, resulted in retrograde double labeling of neurons in the principal trigeminal (Vp) and spinal trigeminal nuclei including subnucleus oralis (Vo), and rostral (Vir) and caudal (Vic) subnucleus interpolaris. Sparse labeling was seen among the root fibers of the facial nerve immediately adjacent to Vp. The data indicated that out of the total population of ipsilateral and contralateral single labeled neurons in TSN subdivisions, double labeled neurons constituted about 11% in Vo, 2% in Vp and Vir, and 1% in Vic. Thus, it seems that out of TSN neurons sending collateral projections to PML of both hemispheres, those in Vo project more frequently than those in Vp, Vir and Vic. The homotopic (corresponding) middle (c and d) PML sublobules receive collateral projections from neurons of all these TSN subdivisions, whereas the caudal (a and b) and rostral (e and f) sublobules seem to be targets of the projection from Vp and Vir. The findings suggest that some TSN neurons may exert simultaneous bilateral modulatory influences upon the regions in various sublobules of both PML.
Neurotrophins promote survival and suppress apoptosis in many populations of neurons. Currently, phosphatidylinositol-3 kinase (PI-3K) is recognized as the main mediator of this protective effect. However, most of the data collected so far on the anti-apoptotic signaling of neurotrophins were obtained using trophic withdrawal paradigms. Recent data from our and other groups indicate that extracellular-signal-regulated kinase 1/2 (Erk1/2) may play a critical role in suppressing neuronal apoptosis triggered by cellular damage. Thus, it appears that either Erk1/2 or PI-3K, depending on the nature of the death-inducing stimulus, can mediate anti-apoptotic signaling of neurotrophins. In this review, we discuss the contribution of Erk1/2 and PI-3K to neuroprotection by neurotrophins. We also present data suggesting possible mechanisms by which these pathways might suppress neuronal death.
Susceptibility of the injured rat brain to seizures depends on the developmental stage at which the injury had been inflicted. Our previous study shows that tacrolimus (FK506) and cyclosporin A (CsA) applied following the injury can also decrease or increase the seizure susceptibility in an age-dependent way. To find possible neuronal substrates of the effects, we examined influences of the agents on the injured brain and on its neuronal population. Rat brains were mechanically injured on postnatal days 6 (P6) or 30 (P30). Twenty minutes and 24 hours following the injury, FK506 or CsA were injected in clinically used pharmaceutical formulations (Prograf or Sandimmun, respectively). The brains were fixed on postnatal day 60 and processed for histological examinations. To detect if negative effects of the injury could be abolished by the treatments, we examined the brain weight, the size of the injured region, and the nerve cell density, including the density of calretinin- and parvalbumin-immunopositive cells. We have found that long-term effects of treatments with the FK506- and CsA-containing pharmaceutical formulations were never better than those of the vehicle alone (Cremophor and ethanol mixture). Moreover, the treatments could even amplify negative consequences of the injury alone. It could, therefore, be concluded that all the neuroprotective effects observed in the present study resulted exclusively from the influence of the vehicle alone. These effects of the brain injury and of subsequent treatments performed at different developmental stages were considered as possible determinants of further increase or decrease in susceptibility to seizures observed in adulthood.
Changes in fitness components including larval stage duration, relative growth rate (RGR), and mass of the gypsy moth, Lymantria dispar L. (Lepidoptera: Lymantriidae), were investigated in caterpillars fed a synthetic diet with or without a cadmiumsupplement (10, 30, 100, 250 Fg Cd/g dry food weight). Morphometric changes of large protocerebral dorsomedial A2 neurosecretory neurons, their nuclei and the electrophoresis profiles of brain proteins were analyzed in the 4th instar gypsy moths fed the examined diets. The duration of the fourth larval instars were prolonged and RGR and body mass reduced if the caterpillars were fed diets containing high concentrations of cadmium(100 and 250 Fg). The size of large A2 dorsomedial neurosecretory neurons and their nuclei were significantly higher in larvae fed the diets supplemented with 10, 100 and 250 Fg Cd. A large amount of neurosecretory material appeared in dorsomedial neurosecretory neurons in larvae fed diets with 100 and 250 Fg Cd. Differences in larval brain protein profiles in the region ofmolecularmass ranges (Mr) of 98kDa, 46kDa and 3.4-6.1 kDa were identified in the experimental groups.
Alzheimer's disease (AD) is a neurodegenerative disorder with a complex etiology and pathogenesis. Chromosome missegregation was proposed two decades ago to be responsible for neurodegeneration in AD patients. It was speculated that the aneuploidy is a result of aberrant cell cycle of neuronal progenitors during adult neurogenesis and/or of mature neurons. There is mounting evidence of increased rate of general aneuploidy and cell cycle reentry in the AD patients' brains, with area-specific pattern. In this review, we discuss the involvement of chromosome instability, genome damage and cell cycle impairment in AD pathology.
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