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
• Názvy látek
• fluorodeoxyglukosa F18 MeSH
• glukosa MeSH
• isothiokyanatany MeSH
• sulforaphane MeSH Prohlížeč
• sulfoxidy MeSH

Brain ischemic injury represents one of the greatest medical challenges for the aging population in developed countries, yet despite strong efforts, possibilities to treat ischemic injury still remain poor. Stroke, the most common type of brain ischemic injury in humans, is caused by brain artery occlusion, and represents a focal form of ischemia, which leads to neuronal loss in the ischemic core, and glial scar formation in the penumbral region around the core. Such glial scar mainly comprises reactive astrocytes, reactive NG2 glia and activated microglia. Reactive astrocytes display distinct features when compared to healthy astroglia, including changes in their morphology, metabolism, gene expression profiles, production of extracellular matrix proteins or proliferation rate. Similarly to astrocytes in the healthy nervous tissue, reactive astrocytes surrounding the glial scar strongly influence the activity of surviving neurons around the ischemic lesion. Bringing insight into pathophysiological functions of reactive astrocytes within the glial scar might thus open new possibilities for stroke treatment. Here, we summarize the properties of reactive astrocytes, with emphasis on the expression and function of ion channels, transporters and neurotransmitter receptors; all of which possess the ability to change the functional state of astrocytes, such as the membrane equilibrium potentials for different ions. This may have major effects on the functioning of surviving neurons, consequently leading to changes in neuronal excitability and progression of secondary pathologies, such as epilepsy. Moreover, we provide possible clues for therapy, based on functional modulation of astrocytic ion transporting mechanisms.

• Klíčová slova
• Reactive astrocytes, brain ischemia, glutamate homeostasis, ion channels, potassium buffering, transporters,
• MeSH
• astrocyty účinky léků   metabolismus   MeSH
• glióza farmakoterapie   metabolismus   MeSH
• homeostáza účinky léků   fyziologie   MeSH
• iontové kanály antagonisté a inhibitory   metabolismus   MeSH
• ischemie mozku farmakoterapie   metabolismus   MeSH
• lidé MeSH
• neurony účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• iontové kanály MeSH

As a consequence of enhanced production of oxygen free radicals, lipid peroxidation leads to the degradation of membrane lipids and disturbances of membrane permeability. Lipid peroxidation increases under stress conditions such as hypoxia, ischemia or acidosis as well as in metabolic diseases, e.g. diabetes mellitus. We have shown that subcomatous doses of insulin (6.0 IU/kg) significantly increase thiobarbituric acid reactive substances (TBARs), especially malondialdehyde (MDA) - the endproduct of lipid peroxidation, in the brain and heart of mice. In our model of insulin-induced hypoglycemia, mice were treated with the neuroprotective, peptide-containing drug Cerebrolysin (100 mg/kg b.w.). Animals were sacrificed by decapitation two or three hours after the injection of tested substance and samples were taken to determine several serum parameters (glucose, total protein, triglycerides and lactic acid) and TBARs in the brain and heart. Although Cerebrolysin was not able to affect serum parameters after subcomatous insulin injection, the drug significantly influenced lipid peroxidation. A single injection of Cerebrolysin already decreased TBARs levels in the brain and heart tissue. Presuming that an increase of TBARs reflects disturbances of the cell membrane, we have documented a promising effect of Cerebrolysin on cell integrity.

• MeSH
• aminokyseliny farmakologie   MeSH
• hypoglykemie krev   chemicky indukované   MeSH
• hypoglykemika farmakologie   MeSH
• inzulin farmakologie   MeSH
• krevní glukóza metabolismus   MeSH
• krevní proteiny metabolismus   MeSH
• kyselina mléčná krev   MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• mozek - chemie účinky léků   MeSH
• myokard metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• neuroprotektivní látky farmakologie   MeSH
• peroxidace lipidů účinky léků   MeSH
• srdce účinky léků   MeSH
• triglyceridy krev   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• cerebrolysin MeSH Prohlížeč
• hypoglykemika MeSH
• inzulin MeSH
• krevní glukóza MeSH
• krevní proteiny MeSH
• kyselina mléčná MeSH
• látky reagující s kyselinou thiobarbiturovou MeSH
• neuroprotektivní látky MeSH
• triglyceridy MeSH

Adipose tissue is now described as an endocrine organ secreting a number of adipokines contributing to the development of inflammation and metabolic imbalance, but also endothelial dysfunction, vascular remodeling, atherosclerosis, and ischemic stroke. Leptin, adiponectin, and resistin are the most studied adipokines which play important roles in the regulation of cardiovascular homeostasis. Leptin and adiponectin mediate both proatherogenic and antiatherogenic responses. Leptin and adiponectin have been linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of ischemic stroke. Resistin, a pro-inflammatory cytokine, is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. The changes in serum levels of novel adipokines apelin, visfatin are also associated with acute ischemic stroke. These adipokines have been proposed as potential prognostic biomarkers of cardiovascular mortality/morbidity and therapeutic targets in patients with cardiometabolic diseases. In this article, we summarize the biologic role of the adipokines and discuss the link between dysfunctional adipose tissue and metabolic/inflammation imbalance, consequently endothelial damage, progression of atherosclerotic disease, and the occurrence of ischemic stroke.

• Klíčová slova
• Adipokines, Adiponectin, Apelin, Atherosclerosis, Inflammation, Ischemic stroke, Leptin, Metabolic changes, Resistin, Visfatin,
• MeSH
• adipokiny metabolismus   MeSH
• ateroskleróza metabolismus   MeSH
• cévní mozková příhoda metabolismus   MeSH
• ischemie metabolismus   MeSH
• lidé MeSH
• nemoci cév metabolismus   MeSH
• nemoci nervového systému metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adipokiny MeSH