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Repeated preconditioning with hyperbaric oxygen induces neuroprotection against forebrain ischemia via suppression of p38 mitogen activated protein kinase
- Source :
- Brain Research. 1301:171-179
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- We previously reported in rats that preconditioning with hyperbaric oxygen (HBO; 100% O(2) 3.5-atomsphere absolute (ATA), 1 h/day for 5 days) provided neuroprotection against transient (8 min) forebrain ischemia possibly through protein synthesis relevant to neurotrophin receptor and inflammatory-immune system. A recent report suggested that HBO-induced neuroprotection is relevant to brain derived neurotrophic factor and its downstream event involving suppression of p38 mitogen activated protein kinase (p38) activation. In the present study, we first performed a dose comparison (1, 2, and 3.5 ATA) of HBO-induced neuroprotection and then investigated pharmacological modification by 10 mg/kg anisomycin (a protein synthesis inhibitor and potent activator for p38) and 200 microg/kg SB203580 (a p38 inhibitor), which were given intraperitoneally 60 and 30 min before every 3.5 ATA-HBO treatment, respectively. Most prominent protective effect on hippocampal CA1 neurons was observed with 3.5 ATA-HBO (survived neurons: 69% [62-73%] vs. untreated: 3.9% [2-8%], 1 ATA: 8.8% [0-26%], 2 ATA-HBO: 46% [22-62%] (median [range]) (7 days after ischemia). Anisomycin abolished a neuroprotective effect (survived neuron: 1.2% [0-7%]). SB203580, when given between administration of anisomycin and HBO treatment, resumed a neuroprotective effect (survived neuron: 52% [37-62%]). The level of phosphorylated p38 at 10-min reperfusion was significantly decreased in 3.5 ATA-HBO group (32% [12-53%] of sham). Single pretreatment with 100 and 200 microg/kg of SB203580 exerted a similar neuroprotective effect (39% [25-51%] and 59% [50-72%]) to 2 and 3.5 ATA-HBO preconditioning, respectively. It is concluded that suppression of p38 phosphorylation plays a key role in HBO-induced neuroprotection and that pretreatment with a p38 inhibitor (SB203580) can provide similar neuroprotection.
- Subjects :
- Male
Cell Survival
Pyridines
p38 mitogen-activated protein kinases
Blotting, Western
Ischemia
Cell Count
Pharmacology
p38 Mitogen-Activated Protein Kinases
Neuroprotection
Brain Ischemia
Brain ischemia
chemistry.chemical_compound
Prosencephalon
Animals
Medicine
Enzyme Inhibitors
Phosphorylation
Rats, Wistar
Ischemic Preconditioning
CA1 Region, Hippocampal
Molecular Biology
Anisomycin
Neurons
Protein Synthesis Inhibitors
Brain-derived neurotrophic factor
Analysis of Variance
Hyperbaric Oxygenation
Dose-Response Relationship, Drug
business.industry
General Neuroscience
Imidazoles
medicine.disease
Rats
Dose–response relationship
Memory, Short-Term
chemistry
Cytoprotection
Anesthesia
Exploratory Behavior
Ischemic preconditioning
Neurology (clinical)
business
Developmental Biology
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1301
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....1781d14faae094a48f765ef40a5ac729