Despite the rising global burden of stroke and its socio-economic implications, the neuroimaging predictors of subsequent cognitive impairment are still poorly understood. We address this issue by studying the relationship of white matter integrity assessed within ten days after stroke and patients' cognitive status one year after the attack. Using diffusion-weighted imaging, we apply the Tract-Based Spatial Statistics analysis and construct individual structural connectivity matrices by employing deterministic tractography. We further quantify the graph-theoretical properties of individual networks. The Tract-Based Spatial Statistic did identify lower fractional anisotropy as a predictor of cognitive status, although this effect was mostly attributable to the age-related white matter integrity decline. We further observed the effect of age propagating into other levels of analysis. Specifically, in the structural connectivity approach we identified pairs of regions significantly correlated with clinical scales, namely memory, attention, and visuospatial functions. However, none of them persisted after the age correction. Finally, the graph-theoretical measures appeared to be more robust towards the effect of age, but still were not sensitive enough to capture a relationship with clinical scales. In conclusion, the effect of age is a dominant confounder especially in older cohorts, and unless appropriately addressed, may falsely drive the results of the predictive modelling.
- MeSH
- bílá hmota * diagnostické zobrazování MeSH
- cévní mozková příhoda * komplikace diagnostické zobrazování MeSH
- difuzní magnetická rezonance MeSH
- kognitivní dysfunkce * diagnostické zobrazování etiologie psychologie MeSH
- lidé MeSH
- senioři MeSH
- stárnutí MeSH
- zobrazování difuzních tenzorů metody MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Epilepsie postihuje asi 0,5–1,5 % populace, z čehož přibližně 30 % pacientů vykazuje farmakorezistenci. Význam MR v diagnostice spočívá zejména v odhalení strukturální etiologie onemocnění, zhodnocení prognózy pacienta a limitovaně i v plánování odpovídající léčby. Navzdory technologickému pokroku v přístrojovém a technickém vybavení zdravotnických pracovišť panuje velká nejednotnost v oblasti protokolů MR využívaných ke strukturálnímu zobrazení mozku u pacientů s epilepsií. Cílem našeho sdělení je doporučení standardizovaného MR protokolu strukturálního zobrazení mozku u pacientů s epilepsií, které vychází ze současných mezinárodních doporučení. Jeho široká implementace umožní v České republice nastavit jednotnou platformu neurozobrazení v těchto indikacích.
Epilepsy affects about 0.5-1.5% of the population, of which approximately 30% of patients are drug-resistant. The importance of MRI in diagnosis lies mainly in the detection of structural etiology of the disease, assessing the patient‘s prognosis and, to a limited extent, planning appropriate treatment. Despite technological advances and technical equipment in medical centers, there is a considerable inconsistency in the MRI protocols used for structural brain imaging in patients with epilepsy. We aim to recommend a standardized MR structural brain imaging protocol for patients with epilepsy based on current international recommendations. Its widespread implementation will enable the establishment of a unified neuroimaging platform in the Czech Republic for these indications.
- Klíčová slova
- strukturální zobrazení mozku,
- MeSH
- epilepsie * diagnostické zobrazování MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- neurozobrazování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVE: Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy. METHODS: We used warm-acclimated (30 °C) mice to characterize the effect of an up to 7-day cold acclimation (6 °C; CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity. RESULTS: Both warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly. CONCLUSIONS: Our results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.
- MeSH
- adrenergní látky metabolismus MeSH
- hnědá tuková tkáň * metabolismus MeSH
- inbrední kmeny myší MeSH
- kosterní svaly metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita metabolismus MeSH
- proteomika * MeSH
- termogeneze fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The present study aimed to elucidate the effect of sulforaphane (a natural isothiocyanate) on oxidative stress and mitochondrial dysfunction during and at selected periods following status epilepticus (SE) induced in immature 12-day-old rats by Li-pilocarpine. Dihydroethidium was employed for the detection of superoxide anions, immunoblot analyses for 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels and respiratory chain complex I activity for evaluation of mitochondrial function. Sulforaphane was given i.p. in two doses (5 mg/kg each), at PD 10 and PD 11, respectively. The findings of the present study indicate that both the acute phase of SE and the early period of epileptogenesis (1 week and 3 weeks following SE induction) are associated with oxidative stress (documented by the enhanced superoxide anion production and the increased levels of 3-NT and 4-HNE) and the persisting deficiency of complex I activity. Pretreatment with sulforaphane either completely prevented or significantly reduced markers of both oxidative stress and mitochondrial dysfunction. Since sulforaphane had no direct anti-seizure effect, the findings suggest that the ability of sulforaphane to activate Nrf2 is most likely responsible for the observed protective effect. Nrf2-ARE signaling pathway can be considered a promising target for novel therapies of epilepsy, particularly when new compounds, possessing inhibitory activity against protein-protein interaction between Nrf2 and its repressor protein Keap1, with less "off-target" effects and, importantly, with an optimal permeability and bioavailability properties, become available commercially.
- MeSH
- faktor 2 související s NF-E2 * metabolismus MeSH
- isothiokyanatany farmakologie MeSH
- KEAP-1 metabolismus MeSH
- krysa rodu rattus MeSH
- mitochondrie metabolismus MeSH
- oxidační stres MeSH
- status epilepticus * metabolismus MeSH
- sulfoxidy metabolismus farmakologie MeSH
- superoxidy metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Perinatal hypoxic-ischemic insult (HII) is one of the main devastating causes of morbidity and mortality in newborns. HII induces brain injury which evolves to neurological sequelae later in life. Hypothermia is the only therapeutic approach available capable of diminishing brain impairment after HII. Finding a novel therapeutic method to reduce the severity of brain injury and its consequences is critical in neonatology. The present paper aimed to evaluate the effect of sulforaphane (SFN) pre-treatment on glucose metabolism, neurodegeneration, and functional outcome at the acute, sub-acute, and sub-chronic time intervals in the experimental model of perinatal hypoxic-ischemic insult in rats. To estimate the effect of SFN on brain glucose uptake we have performed 18F-deoxyglucose (FDG) microCT/PET. The activity of FDG was determined in the hippocampus and sensorimotor cortex. Neurodegeneration was assessed by histological analysis of Nissl-stained brain sections. To investigate functional outcomes a battery of behavioral tests was employed. We have shown that although SFN possesses a protective effect on glucose uptake in the ischemic hippocampus 24 h and 1 week after HII, no effect has been observed in the motor cortex. We have further shown that the ischemic hippocampal formation tends to be thinner in HIE and SFN treatment tends to reverse this pattern. We have observed subtle chronic movement deficit after HII detected by ladder rung walking test with no protective effect of SFN. SFN should be thus considered as a potent neuroprotective drug with the capability to interfere with pathophysiological processes triggered by perinatal hypoxic-ischemic insult.
- MeSH
- fluorodeoxyglukosa F18 terapeutické užití MeSH
- glukosa MeSH
- hypoxie komplikace MeSH
- isothiokyanatany MeSH
- krysa rodu rattus MeSH
- mozek diagnostické zobrazování patologie MeSH
- mozková hypoxie a ischemie * diagnostické zobrazování farmakoterapie MeSH
- novorozená zvířata MeSH
- poranění mozku * MeSH
- sulfoxidy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Balance control is a critical task of daily life, the ability to maintain upright posture becomes of particular concern during aging when the sensory and motor system becomes deteriorated. Falls contribute to the most deaths caused by injury within the aged population, and the mortality rate following a fall is drastically elevated. Longitudinal and reliable assessment of balance control abilities is a critical point in the prediction of increased risk of falling in an elderly population. The primary aim of the study was to evaluate the efficiency of the Homebalance test in the identification of persons being at higher risk of falling. 135 subjects (82 women and 53 men) with geriatric syndrome have been recruited and the Homebalance and the Tinetti Balance test were performed. Results of both tests strongly correlated proving the good performance of the Homebalance test. Standing balance declines with increasing body mass index in both genders. Analysis of fluctuations of the center of pressure (COP) revealed higher frequency and magnitude in mediolateral direction COP movements when compared women to men. A strong negative correlation has been found between Tinetti static balance score and the total length of the COP trajectory during the examination on Homebalance (r = -0.6, p<0.001). Although both methods revealed good performance in detecting balance impairment, Homebalance test possesses higher precision due to the continuous nature of COP-derived parameters. In conclusion, our data proved that the Homebalance test is capable to identify persons with impaired balance control and thus are at higher risk of falling.
- MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- posturální rovnováha * MeSH
- senioři MeSH
- stárnutí MeSH
- úrazy pádem * prevence a kontrola MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Status epilepticus (SE) is a common paediatric emergency with the highest incidence in the neonatal period and is a well-known epileptogenic insult. As previously established in various experimental and human studies, SE induces long-term alterations to brain metabolism, alterations that directly contribute to the development of epilepsy. To influence these changes, organic isothiocyanate compound sulforaphane (SFN) has been used in the present study for its known effect of enhancing antioxidative, cytoprotective, and metabolic cellular properties via the Nrf2 pathway. We have explored the effect of SFN in a model of acquired epilepsy induced by Li-Cl pilocarpine in immature rats (12 days old). Energy metabolites PCr, ATP, glucose, glycogen, and lactate were determined by enzymatic fluorimetric methods during the acute phase of SE. Protein expression was evaluated by Western blot (WB) analysis. Neuronal death was scored on the FluoroJadeB stained brain sections harvested 24 h after SE. To assess the effect of SFN on glucose metabolism we have performed a series of 18F-DG μCT/PET recordings 1 h, 1 day, and 3 weeks after the induction of SE. Responses of cerebral blood flow (CBF) to electrical stimulation and their influence by SFN were evaluated by laser Doppler flowmetry (LDF). We have demonstrated that the Nrf2 pathway is upregulated in the CNS of immature rats after SFN treatment. In the animals that had undergone SE, SFN was responsible for lowering glucose uptake in most regions 1 h after the induction of SE. Moreover, SFN partially reversed hypometabolism observed after 24 h and achieved full reversal at approximately 3 weeks after SE. Since no difference in cell death was observed in SFN treated group, these changes cannot be attributed to differences in neurodegeneration. SFN per se did not affect the glucose uptake at any given time point suggesting that SFN improves endogenous CNS ability to adapt to the epileptogenic insult. Furthermore, we had discovered that SFN improves blood flow and accelerates CBF response to electrical stimulation. Our findings suggest that SFN improves metabolic changes induced by SE which have been identified during epileptogenesis in various animal models of acquired epilepsy.
- Publikační typ
- časopisecké články MeSH
Disruption of the blood-brain barrier (BBB) is a key feature of various brain disorders. To assess its integrity a parametrization of dynamic magnetic resonance imaging (DCE MRI) with a contrast agent (CA) is broadly used. Parametrization can be done quantitatively or semi-quantitatively. Quantitative methods directly describe BBB permeability but exhibit several drawbacks such as high computation demands, reproducibility issues, or low robustness. Semi-quantitative methods are fast to compute, simply mathematically described, and robust, however, they do not describe the status of BBB directly but only as a variation of CA concentration in measured tissue. Our goal was to elucidate differences between five semi-quantitative parameters: maximal intensity (Imax), normalized permeability index (NPI), and difference in DCE values between three timepoints: baseline, 5 min, and 15 min (delta5-0, delta15-0, delta15-5) and two quantitative parameters: transfer constant (Ktrans) and an extravascular fraction (Ve). For the purpose of comparison, we analyzed DCE data of four patients 12-15 days after the stroke with visible CA enhancement. Calculated parameters showed abnormalities spatially corresponding with the ischemic lesion, however, findings in individual parameters morphometrically differed. Ktrans and Ve were highly correlated. Delta5-0 and delta15-0 were prominent in regions with rapid CA enhancement and highly correlated with Ktrans. Abnormalities in delta15-5 and NPI were more homogenous with less variable values, smoother borders, and less detail than Ktrans. Moreover, only delta15-5 and NPI were able to distinguish vessels from extravascular space. Our comparison provides important knowledge for understanding and interpreting parameters derived from DCE MRI by both quantitative and semi-quantitative methods.
Interictal epileptiform discharge (IED) is a traditional hallmark of epileptic tissue that is generated by the synchronous activity of a population of neurons. Interictal epileptiform discharges represent a heterogeneous group of pathological activities that differ in shape, duration, spatiotemporal distribution, underlying cellular and network mechanisms, and their relationship to seizure genesis. The exact role of IEDs in epilepsy is still not well understood, and there remains a persistent dichotomy about the impact on IEDs on seizures. Proseizure, antiseizure, and no impact on ictogenesis have all been described in previous studies. In this article, we review the existing knowledge on the role of interictal discharges in seizure genesis, and we discuss how dynamical approaches to ictogenesis can explain the existing dichotomy about the multifaceted role of IEDs in ictogenesis. This article is part of the Special Issue "NEWroscience 2018".
- MeSH
- elektroencefalografie * MeSH
- epilepsie * MeSH
- lidé MeSH
- neurony MeSH
- záchvaty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Tuberous sclerosis complex (TSC), a multi-system genetic disorder often associated with autism spectrum disorder (ASD), is caused by mutations of TSC1 or TSC2, which lead to constitutive overactivation of mammalian target of rapamycin (mTOR). In several Tsc1+/- and Tsc2+/- animal models, cognitive and social behavior deficits were reversed by mTOR inhibitors. However, phase II studies have not shown amelioration of ASD and cognitive deficits in individuals with TSC during mTOR inhibitor therapy. We asked here if developmental epilepsy, common in the majority of individuals with TSC but absent in most animal models, could explain the discrepancy. METHODS: At postnatal day P12, developmental status epilepticus (DSE) was induced in male Tsc2+/- (Eker) and wild-type rats, establishing four experimental groups including controls. In adult animals (n = 36), the behavior was assessed in the paradigms of social interaction test, elevated plus-maze, light-dark test, Y-maze, and novel object recognition. The testing was carried out before medication (T1), during a 2-week treatment with the mTOR inhibitor everolimus (T2) and after an 8-week washing-out (T3). Electroencephalographic (EEG) activity was recorded in a separate set of animals (n = 18). RESULTS: Both Tsc2+/- mutation and DSE caused social behavior deficits and epileptiform EEG abnormalities (T1). Everolimus led to a persistent improvement of the social deficit induced by Tsc2+/-, while deficits related to DSE did not respond to everolimus (T2, T3). CONCLUSIONS: These findings may contribute to an explanation why ASD symptoms in individuals with TSC, where comorbid early-onset epilepsy is common, were not reliably ameliorated by mTOR inhibitors in clinical studies.
- MeSH
- autistická porucha * MeSH
- haploinsuficience MeSH
- krysa rodu rattus MeSH
- status epilepticus * MeSH
- TOR serin-threoninkinasy genetika MeSH
- tuberin genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
