Abstract
Background and Purpose-This study examines the role of thrombin's protease-activated receptor (PAR)-1, PAR-4 in mediating cyclooxygenase-2 and mammalian target of rapamycin after germinal matrix hemorrhage. Methods-Germinal matrix hemorrhage was induced by intraparenchymal infusion of bacterial collagenase into the right ganglionic eminence of P7 rat pups. Animals were treated with PAR-1, PAR-4, cyclooxygenase-2, or mammalian target of rapamycin inhibitors by 1 hour, and ≤5 days. Results-We found increased thrombin activity 6 to 24 hours after germinal matrix hemorrhage, and PAR-1, PAR-4, inhibition normalized cyclooxygenase-2, and mammalian target of rapamycin by 72 hours. Early treatment with NS398 or rapamycin substantially improved long-term outcomes in juvenile animals. Conclusions-Suppressing early PAR signal transduction, and postnatal NS398 or rapamycin treatment, may help reduce germinal matrix hemorrhage severity in susceptible preterm infants.
Original language | English |
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Pages (from-to) | 1710-1713 |
Number of pages | 4 |
Journal | Stroke |
Volume | 46 |
Issue number | 6 |
DOIs | |
State | Published - Jun 4 2015 |
ASJC Scopus Subject Areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
- Advanced and Specialized Nursing
Keywords
- hydrocephalus
- stroke
- Animals, Newborn
- Cyclooxygenase 2/metabolism
- Anti-Inflammatory Agents, Non-Steroidal/pharmacology
- Rats
- Receptors, Thrombin/antagonists & inhibitors
- Signal Transduction/drug effects
- Receptor, PAR-1/antagonists & inhibitors
- Sirolimus/pharmacology
- Animals
- Brain Injuries/drug therapy
- Sulfonamides/pharmacology
- Cerebral Hemorrhage/drug therapy
- Immunosuppressive Agents/pharmacology
- Nitrobenzenes/pharmacology