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Extracellular space diffusion parameters and metabolism in the rat somatosrensory cortex during recovery from trabsient global ischemia and hypoxia
Zoremba, Norbert ; Syková, Eva (advisor) ; Mareš, Pavel (referee) ; Rokyta, Richard (referee)
Content Abstract .................................................................. ..... ...... ............................ .... 2 Introduction ............................................ ........................................ .................. 4 Aims .................. ................. ................................ ....... ..... . ............ .......... 6 Methods ............................................... ......................................................... ... 7 Results ................ ............................................................................ .................. 9 Discussion .. ... ............... .. ......... .. .......................... ............................. ... ............. 13 References ....... ................................................................ ....................... ........ 20 List of Publications ............. .... .. ............... .. ... .. .......... .. ... ............................... .... 22 Abstract The extracellular space (ECS) of the brain represents the microenvironment of nerve cells and enables the diffusion of neuroactive substances among neurons, axons and glia. Changes in the ECS diffusion parameters during ischemia are well known, but information about changes in ECS diffusion and energy-related metabolite...
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The role of main excitatory and inhibitory transmitters in epileptic seizures and the effect of antiepileptic drugs in the immature brain
Liptáková, Soňa ; Mareš, Pavel (advisor) ; Komárek, Vladimír (referee) ; Šlamberová, Romana (referee)
Epilepsy affects 50 million people worldwide. Approximately 50% of epilepsies start in the infancy and childhood. In addition, there are several age-bound epileptic syndromes which are difficult to treat. Due to these facts, developmental studies of epileptic seizures are of primary importance. Predominance of excitation over inhibition is a mechanism of nearly all types of epileptic seizures. Hypothesis that this compromised balance can be normalized by drugs affecting main excitatory and inhibitory system at different stages of brain development was tested in models with different pathogenesis. Our studies demonstrated that seizures induced by derrangement of GABAergic inhibition can be suppressed by antagonists of NMDA receptors (MK-801) and vice versa seizures with glutamatergic pathogenesis can be affected by drugs potentiating GABAergic system (valproate, ganaxolone) at all developmental stages in immature rats. Analysis of site of action of NMDA receptor antagonists demonstrated reciprocal function of anterior and posterior parts of substantia nigra, structure important for spread of epileptic activity to spinal cord. Special attention was given to an age-dependent model - flexion, emprosthotonic seizures elicited by administration of NMDA. Valproic acid, which potentiates GABAergic inhibition,...
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Developmental changes in expression levels of the chosen subunits of NMDA and AMPA receptors and action of their antagonists on physiological and epileptic phenomena
Szczurowska, Ewa Katarzyna ; Mareš, Pavel (advisor) ; Rokyta, Richard (referee) ; Bendová, Zdeňka (referee)
During early stages of postnatal development, glutamate receptors of NMDA and AMPA type, undergo intensive functional changes due to modifications of their subunit composition (Pachernegg et al., 2012: Paoletti et al., 2013). The NR2B-containing NMDARs (NR2B/NMDARs) and GluA2-lacking AMPARs (Ca 2+ -permeable) that are highly expressed in immature brain, are implicated in increased excitability, seizures generation, excitotoxicity, and neuronal death (Vizi et al., 2013). Pharmacological blockade of these types of receptors by their specific antagonists, can exhibit anticonvulsant effects at early stages of postnatal development. Therefore, we tested the influence of the IEM1460, a specific antagonist of Ca 2+ -permeable AMPARs and the Ro 25-6981 maleate, a highly selective and activity-dependent antagonist of NR2B/NMDARs on physiological excitability and epileptic phenomena induced in immature rats. Anticonvulsant action of IEM1460 was tested in two models of epileptic seizures: pentylenetetrazol (PTZ)- induced convulsions and cortical afterdischarges (ADs), induced in animals at P12, P18 and P25. Our results indicate that the effects of IEM1460 on various types of seizures depend on their sites of origin in the brain, developmental stage, and GluA2 subunit expression profile. To clarify the action...
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Plasticity after focal brain ischemia
Hanáková, Helena ; Mareš, Pavel (advisor) ; Zounková, Irena (referee)
The thesis is focused on brain ischemic injury with an accent on subsequent spontaneous and rehabilitation-induced plastic changes related to motor recovery. General part of thesis describes cortical anatomy and pathophysiology of brain ischaemia including classification of ischemia, ischemic cascade and reperfusion injury. There is also a chapter about spontaneous plasticity and recovery. The main part gives a survey of rat models of focal cortical ischemia, of functional assessment and rehabilitation. Results of rehabilitation-induced cortical plasticity are also presented.
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Motor development after repeated dosing of AMPA receptors antagonist in laboratory rats
Hanzalová, Jitka ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Substance IEM 1460 is an antagonist of AMPA receptors in the brain. It is a derivative of adamantine, which has already been tested in several studies as a potential age-related anticonvulsant. In the research part of the thesis there is a summary of the knowledge about receptors, focusing on AMPA receptors, IEM 1460, epilepsy and ontogenetic development of laboratory rat. The research section evaluates the effect of IEM 1460 on motor skills of a rat in a few postnatal days of its life. To evaluate spontaneous animal motor skills, Open-Field tracking was used, and several specific tests were used to evaluate provoked motor skills. A total of 30 animals were included in the research. Substances (IEM 1460 at 3 mg / kg, IEM 1460 at 10 mg / kg or 2 ml / kg saline) were infused intraperitoneally on five consecutive days (ages P7-P11) and the animals were repeatedly tested at age 12, 15, 18, 21, 25, 31 and 60 days. In this study, IEM 1460 has not been shown to have significant effect on the gross rat motor skills and therefore the substance remains as a serious candidate for age-specific antiepileptic drugs.
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The influence of perinatal hypoxia on motoric development on laboratory rat and means of therapy
Vachovcová, Sylva ; Mareš, Pavel (advisor) ; Stuchlík, Aleš (referee)
Severe perinatal hypoxia represents a substantial brain injury in human newborns. This Diploma thesis is focused on long-term motor outcome of laboratory rat after moderate perinatal hypoxia. We described some behavioral test for detection motor development and presented the influence of perinatal hypoxia on central nervous system. We also discussed an effect of agonists and antagonists of adenosine A1 receptor in brain. The aim of an experimental part was an evaluation of long-term motor behavior in rats affected by perinatal hypoxia. To cause perinatal hypoxia we put pregnant female rats to a hypoxic (10% O2) normobaric room in 11th day of their gestation. The pregnant female rats stayed in hypoxic room until they gave a birth and 6 more days after birth with their litters. For classification of motor development we used battery of tests of motor coordination. These tests correspond to the level of development of the rat. Then a group of rats with perinatal hypoxia was treated by a single administration of an agonist of adenosine A1 receptor 2-chloro-N(6)- cyclopentyladenosin (CCPA) in postnatal day 14. The animals affected by perinatal hypoxia show motor deficits in 3 from 4 selected behavioral tests. Otherwise, this motor behavior was no longer detected in young adults. The rats affected by...
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Swimming as an indicator of normal and altered development of the rat
Vítová, Šárka ; Mareš, Pavel (advisor) ; Pospíšilová, Mariana (referee)
Swimming is an inborn reflex in rats. It represents a complex motor behaviour, which changes significantly throughout the postnatal developmental period. In the current study, development of swimming behaviour was studied using a group of rat pups aged between P5 - P21. A protocol for assessment of swimming in the rat was developed based on literature studies and the results of our own observation on rat swimming. The experiments were conducted using a tank 50x15x30cm, filled with water at 24řC, in which each pup is left for 1 minute or less, if it sinks to the bottom. Swimming was assessed using the following developmental markers: sinking, floating, nose position and swimming movements of the limbs. To study the effect of GABAB receptors ligands on the development of swimming behaviour, three groups of pups aged between P12 - P32 were injected intraperitoneally either physiological solution or 3 mg/kg GABAB receptors antagonist CGP 46381 or 3 mg/kg GABAB receptors agonist baclofen, daily between P7 and P11. Results showed that neither CGP 46381, nor baclofen, alters the development of swimming behaviour compared to a control group. Powered by TCPDF (www.tcpdf.org)
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