Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin synthase gene transfer protect against ischemic cerebral infarction
View abstract on PubMed
Summary
This summary is machine-generated.Gene transfer of cyclooxygenase-1 (COX-1) or COX-1/prostacyclin synthase (PGIS) reduced stroke damage by increasing protective prostaglandins. This COX-1 gene therapy shows promise for treating ischemic stroke.
Area Of Science
- Neuroscience
- Molecular Biology
- Genetics
Background
- Cerebral infarcts result in significant neurological damage.
- Prostaglandins are protective molecules synthesized via cyclooxygenase enzymes.
- Gene transfer offers a potential therapeutic strategy for stroke.
Purpose Of The Study
- To investigate if cyclooxygenase-1 (COX-1)/prostacyclin synthase (PGIS) and COX-1 gene transfer can reduce cerebral infarct volume.
- To determine if this reduction is mediated by increased synthesis of protective prostaglandins.
Main Methods
- Adenoviral vectors carrying COX-1 (Adv-COX-1) or COX-1/PGIS (Adv-COX-1/PGIS) were infused into the lateral ventricles of a rat stroke model.
- Levels of COX-1, PGIS proteins, eicosanoids, and infarct volume were measured.
- The effect of a selective COX-1 inhibitor on neuroprotection was assessed.
Main Results
- Adv-COX-1/PGIS and Adv-COX-1 gene transfer increased COX-1 and PGIS protein levels.
- Adv-COX-1/PGIS selectively augmented prostacyclin levels and significantly reduced infarct volume, even when administered 5 hours post-ischemia.
- Adv-COX-1 increased prostacyclin, suppressed leukotriene levels, and provided similar cerebral protection, which was blocked by a COX-1 inhibitor.
Conclusions
- COX-1/PGIS and COX-1 gene transfer effectively reduce cerebral infarct volume.
- The neuroprotective effects are linked to increased prostacyclin and suppressed leukotriene production.
- COX-1-based gene transfer presents a potential therapeutic approach for ischemic stroke.