|
| |
|
|
Changes of the eExtracellular space diffusion parameters during acute pathological states in the rodent brain and the role of AQP4 channels in cell swelling
Dmytrenko, Lesia ; Vargová, Lýdia (advisor) ; Druga, Rastislav (referee) ; Rokyta, Richard (referee)
1. SUMMARY The diffusion properties of the extracellular space (ECS), which govern the movement of neuroactive substances through its volume and thus extrasynaptic transmission, are profoundly affected in states associated with cell swelling. In this work we compared ECS diffusion parameter changes during acute cell swelling in vivo in models of pilocarpine-induced status epilepticus (SE) and ischemia/anoxia evoked by cardiac arrest. To elucidate mechanisms involving the aquaporin 4 (AQP4) water channel in pathological cell swelling, we used models of hypotonic stress and elevated K+ in coronal slices of genetically modified mice. The ECS diffusion parameters volume fraction ( = ECS volume/total tissue volume), tortuosity factor (2 = apparent diffusion coefficient/free diffusion coefficient) and non-specific uptake (k') were determined by the real-time iontophoretic method, which was the primary method used in my thesis work. Changes in the activity-related extracellular K+ concentration ([K+ ]e) were measured using ion-selective microelectrodes. The apparent diffusion coefficient of water (ADCW) was determined by diffusion-weighted MRI. In both models in vivo, ECS volume fraction and ADCW decreased; these changes were more profound and their time course was faster during terminal ischemia/anoxia in...
|
|
|
Magnetic resonance imaging of central nervous system lymphoma.
Koubská, Eva ; Malíková, Hana (advisor) ; Kalvach, Pavel (referee) ; Druga, Rastislav (referee)
Background: The aim of this study was to describe the morphological signs of the central nervous system lymphoma (CNSL) in magnetic resonance imaging (MRI). We compared morphological characteristics of primary CNSL (PCNSL) and secondary CNSL (SCNSL) and also of PCNSL and glioblastoma (GBM). Methods: We included 64 patients with PCNSL (ten of them were immunocompromised), 21 patients with SCNSL and 54 patients with GBM. The diagnosis was confirmed histologically in all patients. We evaluated morphological signs on the first MRI examination. Additionally, in patients with PCNSL, we evaluated the development of the disease on follow-up examination before histological confirmation of the diagnosis, if available. Results: In most patients with PCNSL (62.5%) the tumor was localized supratentorially and presented as multiple lesions (53.1%) or as a diffuse infiltrative lesion (23.4%). In 87.5% of the patients the lesions reached the brain surface. Infiltration of ependyma was seen in 56.3%, infiltration of meninges in 39.1% and infiltration of cranial nerves in 48.5% of patients. Restriction of diffusion in some part of the tumor was apparent in nearly all patients (97.6%) with PCNSL. After administration of contrast media, marked enhancement was usually seen. In immunocompetent patients, homogenous...
|
|
|
mmunohistochemical analysis of the inhibitory glycine and GABAB receptors in the MNTB
Trojanová, Johana ; Tureček, Rostislav (advisor) ; Druga, Rastislav (referee) ; Vyklický, Ladislav (referee)
Properties of glycine (GlyR) and GABAB (GABABR) receptors were studied in the adult rat medial nucleus of the trapezoid body (MNTB). MNTB belongs among brainstem auditory nuclei. Prevailing cell type in the MNTB is the principal cell (PC). Each PC receives two types of synaptic inputs. Excitatory input originating at contralateral anteroventral cochlear nucleus (AVCN), forms a giant glutamatergic nerve terminal, calyx of Held (CH). Inhibitory inputs are brought by glycinergic and GABAergic fibers of unclear origin. Synaptically released GABA and glycine modulate excitatory synaptic transmission in MNTB via receptors expressed by presynaptic and postsynaptic neurons. The goal of our work was to elucidate both the subcellular distribution and subunit composition of the receptors, thereby extend our knowledge of the function of the receptors in the MNTB. We used immunohistochemical staining methods. The receptors were labelled by specific antibodies localized in the nervous tissue by means of fluorescence or electron microscopy. The experimental work consisted of three phases. During the first phase we revealed that GlyRs in the MNTB form two distinct populations. Postsynaptic receptors form α1β heteromeric clusters on somatodendritic parts of PCs. These clusters colocalize with glycinergic endings...
|
|
| |
|
|
Functional consequences of epileptic seizures and CNS hypoxia-ischemia
Krýsl, David ; Mareš, Jan (advisor) ; Druga, Rastislav (referee) ; Jiruška, Přemysl (referee)
Hypoxic - ischemic CNS lesions and epileptic seizures share many common pathophysiologic features. Basic mechanisms , either detrimental ( excitotoxicity , free radicals, inflammation , changes in permeability of the blood brain barrier , particularly necrotic and apoptotic cell death) , or reparative ( gliosis , neuroplasticity , neurogenesis , vascular proliferation ) occur in Both types of damage , but may be expressed in varying degrees, and may take place in different time term. Hypoxia , but also global and focal ischemia, CNS are in humans and in experimental models under certain conditions accompanied by epileptic seizures. Epileptic seizures vice versa acutely and chronically affect cerebral blood flow (CBF ) . CBF and cerebral metabolism is significantly affected during status epilepticus ( SE). CBF changes can significantly contribute to pathophysiological consequences of seizures and may have links with some of their clinical manifestations (eg Todd's postparoxysmální hemiparesis ( MS Mathews et al. , 2008; Yarnell PR 1975) ) . Focal ischemia, CNS has often consequences in distant , but functionally linked areas ( diaschisis ) . There is a remote influence not only the blood flow and metabolism , but also excitability (Andrews, RJ , 1991 Buchkremer - Ratzmann I. et al. 1996b ) . Also in the...
|
|
|
Histomorphological, biochemical and behavioral profile of animal models of schizophrenia
Kubešová, Anna ; Horáček, Jiří (advisor) ; Libiger, Jan (referee) ; Druga, Rastislav (referee)
The presented work focuses on the animal models of schizophrenia. The general part is dedicated to describing histomorphological and biochemical changes in patients with schizophrenia and basic classification and description of animal models of schizophrenia. The results of 3 studies that deal with histomorphological, biochemical and behavioral abnormalities in the neurodevelopmental model of schizophrenia and in the pharmacological model of schizophrenia induced by the administration of substances that affect the serotonergic system are presented in the special part. In the study No. 1 we demonstrated that the early immune stimulation in rats leads in adulthood to changes in the brain and plasma levels of neurotransmitters and their metabolites, activation of kynurenine pathway of tryptophan metabolism, hypertrophy of astrocytes, reduction of hippocampal volume and decrease of tyrosinhydroxylase immunoreactivity in the substantia nigra pars compacta. The findings of this study support the hypothesis of an important pathophysiological role of the early immune stimulation in schizophrenia and other neuropsychiatric disorders. In the study No. 2 we verified the application of tryptamine (psilocin) and phenylethylamine (mescaline) hallucinogen as phenomenologically valid animal model of schizophrenia....
|
|
|
Role of Islet1, BDNF and nanoparticles in development, function and regeneration of the auditory system
Chumak, Tetyana ; Syka, Josef (advisor) ; Druga, Rastislav (referee) ; Maršálek, Petr (referee)
Detailed knowledge of the role that particular genes and factors play during the development and in the normal function of the auditory system is necessary to develop successful regenerative inner ear therapies. Islet1 transcription factor and brain derived neurothrophic factor (BDNF) have great potential to play a role in regenerative inner ear therapy as both have been shown to be sufficient for self-repair regeneration in cochlea in animal studies. In this study we looked at the roles these two factors play in the development and function of the auditory system. In the transgenic mice used in the study, overexpression of Isl1 affected cell specification during embryonic development, leading to enlargement of the cochleovestibular ganglion and accelerated nerve fiber extension and branching in mutant embryos. The hearing of young transgenic mice was not affected. However, it started to decline in 1-month-old animals. This early onset of age-related hearing loss was found to be a consequence of the neurodegeneration of the olivocochlear system caused by Pax2-driven Isl1 misexpression in the hindbrain. Our data provide the first evidence that the alternation of the olivocochlear system efferent system accelerates the age-related functional decline of hearing without the loss of OHCs. The functional role of...
|
|
|
Neuroanatomical aspects of nonGmotor effects of deep brain stimulation
Růžička, Filip ; Růžička, Evžen (advisor) ; Papežová, Hana (referee) ; Druga, Rastislav (referee)
Summery The underlying mechanisms of weight gain and other affective and cognitive changes after initiation of deep brain stimulation in Parkinson's disease are still unclear. Considering the functional organization within the subthalamic nucleus (STN); limbic, associative and sensorimotor regions residing in the medial, central and later STN respectively, we hypothesized that weight gain may be related to medial localization of stimulation, while motor improvement may be related to lateral localization of stimulation within the STN (study 1). We further hypothesized that stimulation close to the limbic and associative part of the STN may be associated with negative impact on limbic system leading to enhanced anxiety and changes in the hypothalamic- pituitary- adrenal axis (HPA)(study 2). Therefore, the primary aims our study were to assess changes in body weight (study 1) and the hypothalamic- pituitary- adrenal axis (HPA) (study 2) in relation to the position of the active stimulating contact within the nucleus. ...
|
|
|
Magnetic resonance imaging of central nervous system lymphoma.
Koubská, Eva ; Malíková, Hana (advisor) ; Kalvach, Pavel (referee) ; Druga, Rastislav (referee)
Background: The aim of this study was to describe the morphological signs of the central nervous system lymphoma (CNSL) in magnetic resonance imaging (MRI). We compared morphological characteristics of primary CNSL (PCNSL) and secondary CNSL (SCNSL) and also of PCNSL and glioblastoma (GBM). Methods: We included 64 patients with PCNSL (ten of them were immunocompromised), 21 patients with SCNSL and 54 patients with GBM. The diagnosis was confirmed histologically in all patients. We evaluated morphological signs on the first MRI examination. Additionally, in patients with PCNSL, we evaluated the development of the disease on follow-up examination before histological confirmation of the diagnosis, if available. Results: In most patients with PCNSL (62.5%) the tumor was localized supratentorially and presented as multiple lesions (53.1%) or as a diffuse infiltrative lesion (23.4%). In 87.5% of the patients the lesions reached the brain surface. Infiltration of ependyma was seen in 56.3%, infiltration of meninges in 39.1% and infiltration of cranial nerves in 48.5% of patients. Restriction of diffusion in some part of the tumor was apparent in nearly all patients (97.6%) with PCNSL. After administration of contrast media, marked enhancement was usually seen. In immunocompetent patients, homogenous...
|
guest ::
