Activation of microglia associated with lentiviral transduction: A semiautomated method of assessment.

Lentiviral transduction is a powerful tool and widely used in neuroscience research to manipulate gene expression of cells. However, the injection of lentiviral vectors in the brain is not totally benign, it potentially induces focal neuroinflammation. Upon inflammation, microglial cells get activated and can induce major changes in tissue environment, which may interfere with experimental results. In the current study, two weeks after the injection of control viral construction in the dentate gyrus (DG) of rats, an activation of microglia was detected. To access the activation status, we used a fast and accurate method of phenotype detection - measurement of fractal dimension (FD). Microglial morphology is a key indicator of neuroinflammation, therefore FD of microglial cells may serve as a reliable index of inflammation status in the brain. Here we present a detailed description of image processing procedure of images of individual microglial cells. The method allows to preserve the complex structure of microglial cells and their thin processes on the output image, which is important for accurate FD assessment.

[Epigenetic modifications of chromatin in epilepsy: a potential mechanism of pharmacoresistance?] / Épigeneticheskie modifikatsii khromatina pri épilepsii: potentsial'nyi mekhanizm farmakorezistentnosti?

Pharmacoresistance in epilepsy is an important problem from both clinical and fundamental perspectives. The existent hypotheses of pharmacoresistance are based on long term plastic rebuilding of the epileptic brain. One of potential mechanisms mediating such protracted changes are alterations of gene expression induced by epigenetic modifications of chromatin in brain cells of epileptic patients. Recently, changes in DNA methylation and histone post-translational modifications were reported in brain tissues of patients with pharmacoresistant epilepsy. Unfortunately, these data remain fragmentary and contradictory, therefore the results of animal models can partially fill this gap. The authors present a short review of the data concerning a potential role of epigenetic modifications in epilepsy.

[Functions of microglia in the healthy brain: focus on neuroplasticity].

Microglia is in the center of modern research because it is involved in neuroinflammation processes, which is considered as an important part of pathogenesis of many brain pathologies. On the contrary, normal physiological functions of microglia are less studied. Here we review modern data on functioning of microglia in the healthy brain. We consider involvement of microglia in angiogenesis, neurogenesis, synaptogenesis, long-term potentiation, and the mechanisms of microglia-neuron interaction. We further consider modern concept on active interaction of microglia with neurons in developing and healthy mature brain and the essential role of microglia in neuroplasticity mechanisms at various levels.

[Neurodegenerative changes in rat hippocampal areas during the pentylenetetrazole kindling development].

The development of pentylenetetrazole-induced kindling is accompanied by neurodegeneration and neuronal loss in different areas of the hippocampus. However, the data on neurodegeneration development in the dentate gyrus remain controversial. In our study that was performed on 20 Wistar male rats, it was found that the process of neuronal loss was expressed unequally along the dentate gyrus. By the end of pentylenetetrazole kindling development, degenerating cells were present in the superior and inferior blades of the dentate gyrus, whereas the neuronal density in these areas was not reduced. On the other hand, in the angle of the dentate gyrus neuronal loss was already detected at the very early stages of kindling development. These findings allow to suggest a functional heterogeneity of a population of granule cells in relation to their susceptibility to seizure-induced injury.

An early decrease in cell proliferation after pentylenetetrazole-induced seizures.

There are increasing data on the influence of seizures on neurogenesis in the adult brain. However, data on cell proliferation and differentiation during the early stages of kindling are scarce. We have used pentylenetetrazole (PTZ)-induced kindling to investigate the temporal profile of cytogenesis in the germinative zones of adult rat brain. For comparison, we also used a single PTZ-induced generalized tonic-clonic seizure. During kindling development, the density of 5-bromo-2'-deoxyuridine-positive cells demonstrated similar changes in all germinative zones: a dramatic decrease after the first subthreshold PTZ injection, and a gradual increase to the control level following repeated PTZ administration. On the contrary, a single PTZ-induced generalized tonic-clonic seizure was followed by an increase in the number of proliferating cells in both the dentate gyrus and the subventricular zone. These results may indicate the existence of global mechanisms affecting cellular proliferation in adult brain during seizures. Different temporal profiles of neuronal damage and proliferation changes suggest that neurodegeneration is unlikely to be a global proliferation-regulating factor. The data may contribute to better understanding of the initial phase of kindling development and epileptogenesis.

[Evaluation of antiepileptic effects of cortexin in a model of convulsions].

We studied antiepileptic effects of cortexin administered in doses 0,015, 0,15 and 1,0 mg/kg intraperitoneally in solution or intranasally in the complex with nanoparticles in a model of acute and chronic convulsions in rats induced by pentylenetetrazole. In the model of epileptic status, the long-term preliminary administration of cortexin had no effect on convulsions while in the model of chronic convulsions (temporal epilepsy), cortexin had a marked dose-dependent antiepileptic effect. The influence of cortexin on neuroplasticity and its clinical potential are discussed.