After global cerebral hypoxia, many patients are severely disabled even after intensive neurorehabilitation. Secondary mechanisms of brain injury as a result of biochemical and physiological events occur within a period of hours to months, and provide a window of opportunity for therapeutic intervention. Erythropoietin (EPO) has been shown to be neuroprotective in the brain subjected to a variety of injuries. Fifty-nine 3-month-old male Wistar rats were randomly distributed to experimental groups with respect to the housing (enriched environment - EE, standard housing - SH), to hypoxia exposure, and to EPO treatment. An acute mountain sickness model was used as a hypobaric hypoxia simulating an altitude of 8000 m. One half of the animals received erythropoietin injections, while the others were injected saline. Spatial memory was tested in a Morris water maze (MWM). The escape latency and the path length were measured. Better spatial learning in MWM was only seen in the group that received erythropoietin together with enriched environment. EPO administration itself had no influence on spatial memory. The results were very similar for both latencies and path lengths. These results support the idea that after brain injuries, the recovery can be potentiated by EPO administration combined with neurorehabilitation.
- MeSH
- bludiště - učení účinky léků MeSH
- bydlení zvířat * MeSH
- časové faktory MeSH
- chování zvířat účinky léků MeSH
- erythropoetin farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozková hypoxie farmakoterapie patofyziologie psychologie MeSH
- neuroprotektivní látky farmakologie MeSH
- paměť účinky léků MeSH
- potkani Wistar MeSH
- reakční čas účinky léků MeSH
- rekombinantní proteiny farmakologie MeSH
- úniková reakce účinky léků MeSH
- výšková nemoc farmakoterapie patofyziologie psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of our study was to test the hypothesis, whether repeated allopurinol pre-treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability caused by long-term hypoxia exposition in young immature rats. Rat pups were exposed together with their mother in to an intermittent hypobaric hypoxia (simulated altitude of 7 000 m) since the day of birth till the 11th day (youngest experimental group) or 17th day for 8 hours a day. Allopurinol was administered daily immediately before each hypoxia exposition. The duration of evoked afterdischarges (ADs) and the shape of evoked graphoelements were evaluated in 12, 18, 25 and 35-day-old freely moving male pups. Hypobaric hypoxia prolonged the duration of ADs in 12, 18 and 25-day-old rats. The ADs were prolonged in 35-day-old rats only after the first stimulation. Allopurinol shorted the duration of ADs only in 12-day-old pups. In older experimental group the effect of allopurinol treatment was less pronounced.
- MeSH
- alopurinol * farmakologie MeSH
- elektrická stimulace MeSH
- krysa rodu rattus MeSH
- mozek * patofyziologie účinky léků MeSH
- mozková hypoxie * farmakoterapie patofyziologie MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
OBJECTIVES: The effects of ascorbic acid and α-tocopherol pre-treatment on hypoxia induced changes in brain cortex excitability were tested in immature rats exposed chronically to simulated altitude of 7 000 m. METHODS: Rat pups were kept together with their mothers for 8 hours a day in hypobaric chamber since the day of the birth till the postnatal day 11 or 17. Each day immediately before placing to hypobaric chamber pups were pretreated intraperitoneally either with ascorbic acid (100 mg/kg) or α-tocopherol (1 500 mg/kg). Cortical afterdischarges were elicited by repeated stimulation of the right sensorimotor cortex. The duration of evoked cortical afterdischarges was analyzed. RESULTS: Duration of cortical afterdischarges progressively declines with age. Hypoxia prolonged the duration of afterdischarges in 12-, 18- and 25-day-old animals. Pretratment with ascorbic acid or α-tocopherol shorted afterdischarges duration in youngest experimental group when compared with animals exposed to hypoxia only. CONCLUSION: Hypoxia significantly affects the brain cortex excitability by prolonging afterdischarges duration. This effect differs with age. Antioxidant pre-treatment brought about shorter duration of cortical afterdischarges only in the youngest experimental group. The antioxidant effect is therefore age dependent.
- MeSH
- alfa-tokoferol farmakologie MeSH
- antioxidancia farmakologie MeSH
- epilepsie farmakoterapie metabolismus patofyziologie MeSH
- evokované potenciály účinky léků MeSH
- krysa rodu rattus MeSH
- kyselina askorbová farmakologie MeSH
- mozková hypoxie farmakoterapie metabolismus patofyziologie MeSH
- mozková kůra účinky léků růst a vývoj metabolismus MeSH
- novorozená zvířata MeSH
- oxidační stres účinky léků fyziologie MeSH
- těhotenství MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hypoxické poškození mozku v průběhu prenatálního nebo postnatálního období je častou příčinou lidské morbidity i mortality. Nedostatek kyslíku či selhání antioxidačních mechanismů v období reperfuze vyvo¬lává závažné změny vnitřního prostředí, které mohou vyvolat jak morfologické, tak i funkční důsledky, a to i v centrálním nervovém systému.
Hypoxic injury of the brain during the prenatal and/or postnatal period represents a frequent cause of human morbidity and mortality. Oxygen deficiency or low capacity of antioxidant mechanisms during the reperfu- sion period cause serious changes in homeostasis, which can result in structural and functional impairment of the central nervous system.
- MeSH
- antioxidancia aplikace a dávkování farmakologie chemie MeSH
- energetický metabolismus MeSH
- enzymy aplikace a dávkování farmakologie chemie MeSH
- fyziologická adaptace fyziologie MeSH
- lidé MeSH
- mozková hypoxie farmakoterapie klasifikace patofyziologie MeSH
- neurony enzymologie metabolismus MeSH
- neuroplasticita fyziologie MeSH
- Check Tag
- lidé MeSH
- MeSH
- hipokampus patologie účinky léků MeSH
- krysa rodu rattus MeSH
- mozková hypoxie farmakoterapie MeSH
- neuropeptidy aplikace a dávkování terapeutické užití MeSH
- otrava oxidem uhelnatým farmakoterapie MeSH
- šířící se kortikální deprese farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- apoptóza MeSH
- dítě MeSH
- hypotermie metody MeSH
- ischemie mozku etiologie farmakoterapie terapie MeSH
- lidé MeSH
- mozková hypoxie etiologie farmakoterapie terapie MeSH
- nekróza MeSH
- neonatologie MeSH
- neurony MeSH
- novorozenec MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- akční potenciály účinky léků MeSH
- antioxidancia terapeutické užití MeSH
- hipokampus patofyziologie MeSH
- karboliny terapeutické užití MeSH
- krysa rodu rattus MeSH
- mozková hypoxie farmakoterapie patofyziologie MeSH
- nervový přenos genetika MeSH
- sympatická ganglia fyziologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
