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.
Stroke is despite of progressive improvements in treatment and reperfusion strategies one of the most devastating human pathology. However, as quality of acute health care improves and more people survive ischemic attack, healthcare specialists have to solve new challenges to preserve reasonable quality of life to these patients. Thus, novel approaches which prevents comorbidities of stroke and improve quality of life of stroke survivors in general has to be developed and experimentally tested. The aim of the present paper was to establish reliable rat model of middle cerebral occlusion and set of methods allowing selection of animals suitable for long-term experiments. We have compared mortality rates, cerebral blood flow and extension of ischemic lesion induced by intraluminal filament in three widely used outbred rat strains. We have additionally used an animal 18F-DG PET scans to verify its reliability in noninvasive detection of ischemic infarct in acute period (24 h after MCAO) for selecting animals eligible for long survival experiments. Our data clearly indicates that high variability between rat strains might negatively influence stroke induction by intraluminal thread occlusion of middle cerebral artery. Most reliable outbred rat strain in our hands was Sprague-Dawley where maximal reduction of cerebral blood flow and extensive ischemic lesion was observed. Contrary, Wistar rats exhibited higher mortality and Long-Evans rats significantly smaller or no ischemic region in comparison to Sprague-Dawley. Additionally, we have confirmed a positron emission tomography with 18F-fluorodeoxyglucose as suitable method to assess extension of ischemic region in acute period after the experimental arterial occlusion in rats.
Manual review of EEG records, as it is performed in common medical practice, is very time-consuming. There is an effort to make this analysis easier and faster for neurologists by using systems for automatic EEG graphoelements recognition. Such a system is composed of three steps: (1) segmentation, which is a subject of this article, (2) features extraction and (3) classification. Precision of classification, and thereby the whole recognition, is strongly affected by the quality of preceding segmentation procedure, which depends on the method of segmentation and its parameters. In this paper, Varri's method for segmentation of real epileptic EEG signals is used. Effect of input parameters on segmentation outcome is discussed and parameters values are proposed to achieve optimal outcome suitable for the following classification and graphoelements recognition. Only the results of segmentation are presented in this paper.
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 (Δ5-0, Δ15-0, Δ15-5) 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. Δ5-0 and Δ15-0 were prominent in regions with rapid CA enhancement and highly correlated with Ktrans. Abnormalities in Δ15-5 and NPI were more homogenous with less variable values, smoother borders, and less detail than Ktrans. Moreover, only Δ15-5 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.
Status epilepticus (SE) is a common neurological emergency in children and a well-known epileptogenic insult. Neonates are extremely susceptible to seizures in the neonatal period due to the higher vulnerability. Neonatal SE is associated with significant mortality and morbidity. There is an evident need for attention on neonatal SE in research due to the incredibly limited diagnostic and treatment options in current neonatology, and its serious long-term consequences. The aim of the present study was to characterize the glycoprofiles in the pilocarpine-induced SE model in immature rats to assess the overall N-glycans composition. To induce lithium-pilocarpine (Li-Pilo) SE male Wistar rat pups were pretreated with lithium chloride (127 mg/kg, n=11) on the 11th postnatal day. After 24 hours, the lithium pre-treated pups were administered either with pilocarpine intraperitoneally (i.p.) (35 kg/g, n=6) or saline (n=5) in the control group (Control). On the 19th postnatal day, serum was collected and the analytical procedures were done by mass spectrometry (MS) analytics on matrix-assisted laser desorption/ionization in combination with a time-of-flight detector (MALDI-TOF/MS). Analyzed data were processed by FlexAnalysis (Bruker Daltonics) and GlycoWorkbench software. There were 21 N-glycans that were identified, appointed, and sorted with special emphasis on their structure. We have demonstrated the significant changes in terms of N-glycans sialylation in Li-Pilo compared to the Control. We also observed some other remodelation trends in different portions of relative intenstities of N-glycan clusters according to their glycan type. Our preliminary findings have laid the foundation for additional investigation into glycosylation alterations in the SE in immature rats.
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) μCT/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.
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