Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.

• MeSH
• Behavior, Animal drug effects   MeSH
• Rats MeSH
• Locomotion drug effects   MeSH
• Methamphetamine toxicity   MeSH
• Rotarod Performance Test MeSH
• Paternal Exposure * MeSH
• Sex Characteristics MeSH
• Reflex, Righting drug effects   MeSH
• Rats, Wistar MeSH
• Sensorimotor Cortex drug effects   growth & development   MeSH
• Sex Factors MeSH
• Central Nervous System Stimulants toxicity   MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Pacienti s cervikální dystonií jsou často významně limitováni v pracovních i společenských aktivitách. Botulotoxin je v současné době moderní a účinnou léčbou fokální dystonie, ale mechanismus jeho účinku na úrovni CNS není znám. Cílem tohoto projektu je srovnat aktivaci kortikálních oblastí aktivovaných volným pohybem končetiny na straně vedoucího svalu dystonie před a po aplikaci botulotoxinu; a dále korelovat změny mozkové aktivace s mírami integrity somatosenzorických okruhů. K dosažení těchto cílů použijeme motorické testy, funkční magneticko-rezonanční zobrazování a neurofyziologické metody. Vyšetření budou prováděna u botulotoxin-naivních pacientů s cervikální dystonií před zahájením terapie botulotoxinem a následně také na vrcholu jeho klinického efektu po čtyřech týdnech od aplikace. Ve stejném protokolu (před aplikací a čtyři týdny po aplikaci) budou prováděna vyšetření dále v šestém, dvanáctém a čtyřiadvacátém měsíci pravidelné terapie botulotoxinem.; Patients suffering from cervical dystonia (CD) are very often notably limited in working and social activities. Botulinum toxin (BoNT-A) is currently considered to be the one of the most effective therapeutic options. However, the complete mechanism of its effect on the central level is not yet known. To compare the sensorimotor network beyond the representation of the affected body part in CD patients and the possible cortical changes induced by BoNT-A treatment, functional magnetic resonance imaging (fMRI) and paired transcranial magnetic stimulation (pTMS) will be employed. These fMRI, pTMS and clinical examinations will be performed in BoNT-A naive CD patients at the beginning of regular BoNT-A treatment and will be repeated in the time of the best clinical effect four weeks after the BoNT-A injection. In order to evaluate the early and late changes due to BoNT-A treatment, this protocol will be repeated in the 6th, 12th and 24th month of treatment.

• MeSH
• Botulinum Toxins, Type A pharmacology   therapeutic use   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Neurophysiological Monitoring methods   MeSH
• Psychomotor Performance MeSH
• Sensorimotor Cortex drug effects   MeSH
• Torticollis drug therapy   MeSH
• Transcranial Magnetic Stimulation methods   MeSH
• Check Tag
• Humans MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurologie
• farmacie a farmakologie
• farmakoterapie
• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

BACKGROUND: Olanzapine is a frequently used atypical antipsychotic drug known to exert structural brain alterations in animals. This study investigated whether chronic olanzapine exposure alters regional blood brain perfusion assessed by Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI) in a validated model of olanzapine-induced metabolic disturbances. An effect of acute olanzapine exposure on brain perfusion was also assessed for comparison. METHODS: Adult Sprague-Dawley female rats were treated by intramuscular depot olanzapine injections (100 mg/kg every 14 days) or vehicle for 8 weeks. ASL scanning was performed on a 9.4 T Bruker BioSpec 94/30USR scanner under isoflurane anesthesia. Serum samples were used to assay leptin and TNF-α level while brains were sliced for histology. Another group received only one non-depot intraperitoneal dose of olanzapine (7 mg/kg) during MRI scanning, thus exposing its acute effect on brain perfusion. RESULTS: Both acute and chronic dosing of olanzapine resulted in decreased perfusion in the sensorimotor cortex, while no effect was observed in the piriform cortex or hippocampus. Furthermore, in the chronically treated group decreased cortex volume was observed. Chronic olanzapine dosing led to increased body weight, adipose tissue mass and leptin level, confirming its expected metabolic effects. CONCLUSION: This study demonstrates region-specific decreases in blood perfusion associated with olanzapine exposure present already after the first dose. These findings extend our understanding of olanzapine-induced functional and structural brain changes.

• MeSH
• Antipsychotic Agents administration & dosage   adverse effects   MeSH
• Magnetic Resonance Imaging MeSH
• Cerebrovascular Circulation drug effects   MeSH
• Olanzapine administration & dosage   adverse effects   MeSH
• Rats, Sprague-Dawley MeSH
• Drug Administration Schedule MeSH
• Sensorimotor Cortex blood supply   diagnostic imaging   drug effects   MeSH
• Organ Size drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Clinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.

• MeSH
• Circle of Willis diagnostic imaging   drug effects   embryology   MeSH
• Hippocampus blood supply   diagnostic imaging   drug effects   embryology   MeSH
• Rats MeSH
• Humans MeSH
• Magnetic Resonance Angiography methods   MeSH
• Methylazoxymethanol Acetate toxicity   MeSH
• Disease Models, Animal MeSH
• Cerebrovascular Circulation drug effects   MeSH
• Neurogenesis drug effects   MeSH
• Schizophrenia chemically induced   diagnosis   MeSH
• Sensorimotor Cortex blood supply   diagnostic imaging   drug effects   embryology   MeSH
• Behavior Observation Techniques MeSH
• Pregnancy MeSH
• Dronabinol toxicity   MeSH
• Prenatal Exposure Delayed Effects chemically induced   diagnostic imaging   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Botulinum toxin type A (BoNT) is considered an effective therapeutic option in cervical dystonia (CD). The pathophysiology of CD and other focal dystonias has not yet been fully explained. Results from neurophysiological and imaging studies suggest a significant involvement of the basal ganglia and thalamus, and functional abnormalities in premotor and primary sensorimotor cortical areas are considered a crucial factor in the development of focal dystonias. Twelve BoNT-naïve patients with CD were examined with functional MRI during a skilled hand motor task; the examination was repeated 4 weeks after the first BoNT injection to the dystonic neck muscles. Twelve age- and gender-matched healthy controls were examined using the same functional MRI paradigm without BoNT injection. In BoNT-naïve patients with CD, BoNT treatment was associated with a significant increase of activation in finger movement-induced fMRI activation of several brain areas, especially in the bilateral primary and secondary somatosensory cortex, bilateral superior and inferior parietal lobule, bilateral SMA and premotor cortex, predominantly contralateral primary motor cortex, bilateral anterior cingulate cortex, ipsilateral thalamus, insula, putamen, and in the central part of cerebellum, close to the vermis. The results of the study support observations that the BoNT effect may have a correlate in the central nervous system level, and this effect may not be limited to cortical and subcortical representations of the treated muscles. The results show that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in CD even the first BoNT injection is associated with changes in sensorimotor activation. The differences in activation between patients with CD after treatment and healthy controls at baseline were no longer present.

• MeSH
• Afferent Pathways diagnostic imaging   drug effects   MeSH
• Botulinum Toxins, Type A therapeutic use   MeSH
• Adult MeSH
• Oxygen blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Statistics, Nonparametric MeSH
• Neuromuscular Agents therapeutic use   MeSH
• Image Processing, Computer-Assisted MeSH
• Psychomotor Performance drug effects   MeSH
• Aged MeSH
• Sensorimotor Cortex diagnostic imaging   drug effects   MeSH
• Torticollis * diagnostic imaging   drug therapy   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Ro 25-6981 maleate is a highly selective and activity-dependent antagonist of NMDA ionotropic glutamate receptors containing NR2B subunit (NR2B/NMDARs). The aim of our study was to investigate the influence of Ro 25-6981 administration in developing rats on physiological (single and paired pulse cortical interhemispheric evoked potentials) and epileptic brain activity (cortical afterdischarges (ADs)). Electrophysiological experiments were performed in animals with epidurally implanted electrodes at postnatal days (P) P12, P18, and P25. The drug was injected intraperitoneally at a dose of 1 or 3mg/kg. Control animals were injected with saline (1ml/kg). Single interhemispheric responses were evoked with 0.5-ms biphasic pulses with intensities increasing from 0.4 to 5mA, paired-pulse responses were elicited by twofold threshold intensity. The ADs were elicited by series of 15-s of 1-ms pulses at 8-Hz frequency. Firstly, six stimulations with stable suprathreshold intensity repeated at 30-min intervals were used to determine the time course of Ro 25-6981 effects against ADs in P12 animals. Secondly, similar experiment was performed in all age groups of animals but with 20-min intervals as well as a further experiment using stimulations with stepwise intensities increasing at 10-min intervals from 0.2 to 15 mA. Pretreatment with the 3-mg/kg (but not the lower) dose of Ro 25-9681 decreased significantly the amplitude of single responses evoked with higher stimulation intensities in P12 and P18 animals. Both doses affected responses in P25 animals, only the 1-mg/kg dose was more efficacious than the 3-mg/kg one. Paired pulse responses were not affected by either dose of Ro 25-6981 in any age group. Ro 25-9681 clearly influenced the duration of ADs only in P12 animals. The 1-mg/kg dose did not change the duration of ADs whereas the 3-mg/kg dose suppressed progressive prolongation of ADs with repeated stimulations. This effect was seen even 110-min after the drug injection. The modification of ADs, i.e. stimulations with stepwise increasing intensities (10 min intervals) was used to demonstrate possible dependence on activity. The Ro 25-6981 was administered immediately after the 4-mA stimulation (i.e. when rats experienced six ADs on the average). The 3-mg/kg dose resulted in shorter ADs after high stimulation intensities in P12. There were no significant effects in older animals, only a tendency to ADs shortening was observed in P25 rats. In conclusion, our results indicate that Ro 25-6981 as a selective antagonist of NR2B/NMDARs exhibit age- and activation-dependent anticonvulsant action at early postnatal development. In contrast, the influence of Ro 25-6981 on physiological excitability induced by single pulse stimulation of sensorimotor cortex does not depend on age. This compound may thus represent a useful antiepileptic agent in immature brain since its action against ADs prolongation can be observed even 110 min after the single administration of the drug.

• MeSH
• Anticonvulsants administration & dosage   MeSH
• Electric Stimulation MeSH
• Phenols administration & dosage   MeSH
• Rats MeSH
• Membrane Potentials drug effects   MeSH
• Piperidines administration & dosage   MeSH
• Rats, Wistar MeSH
• Receptors, N-Methyl-D-Aspartate antagonists & inhibitors   MeSH
• Sensorimotor Cortex drug effects   physiopathology   MeSH
• Age Factors MeSH
• Seizures drug therapy   physiopathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND AND PURPOSE: Botulinum toxin (BoNT) treatment relieves focal arm spasticity after stroke, likely acting at several hierarchical levels of the motor system. The central correlate of BoNT-induced spasticity relief may be detected using repeated functional MRI (fMRI) during motor task. METHODS: Five patients (4 males, 1 female, mean age 67 years) with hemiparesis and distal arm spasticity after chronic ischemic stroke were studied. FMRI was performed while moving the paretic hand in three sessions: before and 4 and 11 weeks after BoNT treatment. RESULTS: Arm spasticity significantly decreased following BoNT treatment across the group (mean modified Ashworth scale change .6). FMRI prior to BoNT treatment showed extensive bilateral active networks, whereas post-BoNT activation was limited to midline and contralateral sensorimotor cortices, and the third examination, when the toxin effect has worn off, again showed extensive activation similar to pre-BoNT examination. Post-BoNT session 2 compared to sessions 1 and 3 demonstrated a significantly less activation in contralateral frontoparietal areas including inferior frontal, postcentral, and middle frontal gyri as well as transient crossed cerebellar activation. CONCLUSION: Relief of post-stroke arm spasticity may be associated with changes at several hierarchical levels of the cortical sensorimotor system, including the prefrontal cortex.

• MeSH
• Botulinum Toxins, Type A therapeutic use   MeSH
• Stroke complications   drug therapy   physiopathology   MeSH
• Evoked Potentials * MeSH
• Middle Aged MeSH
• Humans MeSH
• Neuromuscular Agents therapeutic use   MeSH
• Arm MeSH
• Movement MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sensorimotor Cortex drug effects   physiopathology   MeSH
• Muscle Spasticity drug therapy   etiology   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Electroencephalography MeSH
• Epilepsy diagnostic imaging   chemically induced   MeSH
• Evoked Potentials physiology   drug effects   MeSH
• Contingent Negative Variation physiology   drug effects   MeSH
• Rats MeSH
• Cerebral Cortex * physiology   physiopathology   drug effects   MeSH
• Pentylenetetrazole administration & dosage   pharmacology   MeSH
• Sensorimotor Cortex physiopathology   drug effects   MeSH
• Cortical Spreading Depression MeSH
• Seizures * chemically induced   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH

• MeSH
• Electroencephalography MeSH
• Epilepsy * chemically induced   MeSH
• Haplorhini MeSH
• Animals, Laboratory MeSH
• Membrane Potentials physiology   drug effects   MeSH
• Models, Animal MeSH
• Brain Waves drug effects   MeSH
• Neurons physiology   drug effects   MeSH
• Sensorimotor Cortex physiopathology   drug effects   MeSH

• MeSH
• Action Potentials physiology   drug effects   MeSH
• Electroshock MeSH
• Electroencephalography methods   MeSH
• Epilepsy diagnostic imaging   etiology   MeSH
• Rabbits MeSH
• Models, Animal MeSH
• Pentylenetetrazole administration & dosage   pharmacology   MeSH
• Sensorimotor Cortex physiopathology   drug effects   MeSH
• Check Tag
• Rabbits MeSH