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Search: WFRF:(Kokaia Z)

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1.
  • Bengzon, J, et al. (author)
  • Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling
  • 1993
  • In: Neuroscience. - 0306-4522. ; 53:2, s. 433-446
  • Journal article (peer-reviewed)abstract
    • Levels of messenger RNA for nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and the tyrosine kinase receptors trkA, trkB and trkC have been studied using in situ hybridization in the rat brain 2 h and four weeks after kindling-induced seizures. Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures. Brain-derived neurotrophic factor messenger RNA levels were also increased bilaterally in the CA1-CA3 regions, amygdala and the piriform, entorhinal, perirhinal, retrosplenial and temporal cortices after generalized seizures. The magnitude of the increases was similar throughout the development of kindling and in the fully kindled brain. No changes of trkA messenger RNA were observed. In amygdalar kindling, elevated brain-derived neurotrophic factor messenger RNA levels developed more rapidly in the amygdala-piriform cortex than after stimulation in the hippocampus but changes in the hippocampal formation were only seen in few animals. Intraventricular 6-hydroxydopamine or a bilateral fimbria-fornix lesion did not alter basal expression or seizure-evoked changes in messenger RNA levels for neurotrophins or trk receptors but increased the number of animals exhibiting elevated levels after the first stimulation, probably due to a prolongation of seizure activity. Both in sham-operated and fimbria-fornix-lesioned rats seizure activity caused a marked reduction of neurotrophin-3 messenger RNA levels in dentate granule cells. The results indicate that activation of the brain-derived neurotrophic factor gene, at least in dentate granule cells, is an "all-or-none" type of response and dependent on the duration but not the severity of seizures or the stage of kindling epileptogenesis. Changes in brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and trkB and trkC were observed concomitantly in the dentate gyrus, which suggests that seizure activity sets in motion a cascade of genomic events possibly mediated via a common mechanism. Since altered messenger RNA levels outside hippocampus were detected only for brain-derived neurotrophic factor, neurotrophin and trk gene expression in these regions seems to be regulated differently.
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  • Kokaia, Z, et al. (author)
  • BDNF makes cultured dentate granule cells more resistant to hypoglycaemic damage
  • 1994
  • In: NeuroReport. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4965 .- 1473-558X. ; 5:10, s. 4-1241
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to explore whether brain-derived neurotrophic factor (BDNF) can improve neuronal survival in cell cultures of rat dentate gyrus subjected to a hypoglycaemic insult. Glucose deprivation for 15 h caused severe neuronal loss (about 70%). BDNF added either 24 h before or 4 h after onset of hypoglycaemia completely protected granule cells against this insult-induced damage. Nerve growth factor (NGF) had similar effects. These findings support the hypothesis that the rapid upregulation of BDNF mRNA in dentate granule cells after brief periods of hypoglycaemic coma and other insults is a local protective mechanism.
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  • Pratt, G D, et al. (author)
  • Differential regulation of N-methyl-D-aspartate receptor subunit messenger RNAs in kindling-induced epileptogenesis
  • 1993
  • In: Neuroscience. - 0306-4522. ; 57:2, s. 18-307
  • Journal article (peer-reviewed)abstract
    • N-methyl-D-aspartate-receptors are implicated in several neuropathological conditions including epilepsy. As a model of complex partial seizures, rapid hippocampal kindling was chosen to investigate changes in the expression of messenger RNAs encoding the N-methyl-D-aspartate-receptor subunits NR1, NR2A and NR2B both during and in the period immediately following the induction of the kindled state. The study demonstrates a cell-specific, time-dependent modulation of the N-methyl-D-aspartate-receptor subunit messenger RNAs almost entirely restricted to the granule cells of the dentate gyrus. In partially kindled animals (10 stimulations), while the NR1 subunit messenger RNA remained unaltered after a period of 2 h, the NR2A and NR2B subunit messenger RNAs were bilaterally reduced in dentate gyrus granule cells by around 50% below control values. In fully kindled animals (40 stimulations), a progressive reduction in NR1 subunit messenger RNA levels in the dentate gyrus was observed, being maximal after 4 h (-67%). At the same time point, NR2A and NR2B transcript levels were transiently increased by 102% and 46% above control values, respectively. These data point to a differential regulation of N-methyl-D-aspartate-receptor subunit messenger RNAs. No alterations were detected in pyramidal cells. Long-term maintenance of the kindled state was not associated with alterations in N-methyl-D-aspartate-receptor subunit messenger RNAs since control levels of messenger RNA were attained by 12 h and persisted for at least five days. The early changes in messenger RNAs described in this study indicate that the expression of N-methyl-D-aspartate-receptor subunits is under independent regulatory control. This phenomenon may contribute to epileptogenesis and to kindling-associated plasticity by mediating a structural reorganization of N-methyl-D-aspartate-receptors, leading to an altered excitability of dentate gyrus granule cells.
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8.
  • Svanidze, I. K., et al. (author)
  • Differentsirovka neironov golubovatogo mesta posle ikh allotransplantatsii v predvaritel'no denervirovannyi gippokamp belykh krys.
  • 1997
  • In: Morfologiia. - 1026-3543. ; 111:2, s. 35-39
  • Journal article (peer-reviewed)abstract
    • The suspension of embryonic locus coeruleus (LC) was transplanted into outbred albino rat hippocampus after its preliminary 6-hydroxy-dopamine-induced denervation. Immunohistochemical and morphometric analysis revealed that 3 months after the transplantation, embryonic noradrenergic LC cells which have completed their histogenesis in recipient hippocampus, appear as differentiated multipolar and fusiform cells, typical to LC. Intrahippocampal allotransplants of rat embryonic LC were also demonstrated to normalize the level of orientation activity in an open area, that was significantly reduced after administration of 6-hydroxy-dopamine to the animals.
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  • Kokaia, Z., et al. (author)
  • Transplantation of reprogrammed neurons for improved recovery after stroke
  • 2017
  • In: Functional Neural Transplantation IV Translation to Clinical Application, Part B. - : Elsevier. - 0079-6123. - 9780128138793 ; 231, s. 245-263
  • Book chapter (peer-reviewed)abstract
    • Somatic cells such as fibroblasts, reprogrammed to induced pluripotent stem cells, can be used to generate neural stem/progenitor cells or neuroblasts for transplantation. In this review, we summarize recent studies demonstrating that when grafted intracerebrally in animal models of stroke, reprogrammed neurons improve function, probably by several different mechanisms, e.g., trophic actions, modulation of inflammation, promotion of angiogenesis, cellular and synaptic plasticity, and neuroprotection. In our own work, we have shown that human skin-derived reprogrammed neurons, fated to cortical progeny, integrate in stroke-injured neuronal network and form functional afferent synapses with host neurons, responding to peripheral sensory stimulation. However, whether neuronal replacement plays a role for the improvement of sensory, motor, and cognitive deficits after transplantation of reprogrammed neurons is still unclear. We conclude that further preclinical studies are needed to understand the therapeutic potential of grafted reprogrammed neurons and to define a road map for their clinical translation in stroke.
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