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
- antipsychotika aplikace a dávkování škodlivé účinky MeSH
- magnetická rezonanční tomografie MeSH
- mozkový krevní oběh účinky léků MeSH
- olanzapin aplikace a dávkování škodlivé účinky MeSH
- potkani Sprague-Dawley MeSH
- rozvrh dávkování léků MeSH
- senzorimotorický kortex krevní zásobení diagnostické zobrazování účinky léků MeSH
- velikost orgánu účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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
- circulus arteriosus Willisi diagnostické zobrazování účinky léků embryologie MeSH
- hipokampus krevní zásobení diagnostické zobrazování účinky léků embryologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- magnetická rezonanční angiografie metody MeSH
- methylazoxymethanolacetát toxicita MeSH
- modely nemocí na zvířatech MeSH
- mozkový krevní oběh účinky léků MeSH
- neurogeneze účinky léků MeSH
- schizofrenie chemicky indukované diagnóza MeSH
- senzorimotorický kortex krevní zásobení diagnostické zobrazování účinky léků embryologie MeSH
- techniky pozorování chování MeSH
- těhotenství MeSH
- tetrahydrokanabinol toxicita MeSH
- zpožděný efekt prenatální expozice chemicky indukované diagnostické zobrazování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
- aferentní nervové dráhy diagnostické zobrazování účinky léků MeSH
- botulotoxiny typu A terapeutické užití MeSH
- dospělí MeSH
- kyslík krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- neparametrická statistika MeSH
- nervosvalové látky terapeutické užití MeSH
- počítačové zpracování obrazu MeSH
- psychomotorický výkon účinky léků MeSH
- senioři MeSH
- senzorimotorický kortex diagnostické zobrazování účinky léků MeSH
- tortikolis * diagnostické zobrazování farmakoterapie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In Vojta physiotherapy, also known as reflex locomotion therapy, prolonged peripheral pressure stimulation induces complex generalized involuntary motor responses and modifies subsequent behavior, but its neurobiological basis remains unknown. We hypothesized that the stimulation would induce sensorimotor activation changes in functional magnetic resonance imaging (fMRI) during sequential finger opposition. Thirty healthy volunteers (mean age 24.2) underwent two randomized fMRI sessions involving manual pressure stimulation applied either at the right lateral heel according to Vojta, or at the right lateral ankle (control site). Participants were scanned before and after the stimulation when performing auditory-paced sequential finger opposition with their right hand. Despite an extensive activation decrease following both stimulation paradigms, the stimulation of the heel specifically led to an increase in task-related activation in the predominantly contralateral pontomedullary reticular formation and bilateral posterior cerebellar hemisphere and vermis. Our findings suggest that sustained pressure stimulation of the foot is associated with differential short-term changes in hand motor task-related activation depending on the stimulation. This is the first evidence for brainstem modulation after peripheral pressure stimulation, suggesting that the after-effects of reflex locomotion physiotherapy involve a modulation of the pontomedullary reticular formation.
- MeSH
- dospělí MeSH
- funkční lateralita fyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování fyziologie MeSH
- počítačové zpracování obrazu MeSH
- senzorimotorický kortex diagnostické zobrazování fyziologie MeSH
- tlak * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH