Prostaglandin E2 EP1 receptor inhibition fails to provide neuroprotection in surgically induced brain-injured mice.

Abstract

Recent trials have shown that the prostaglandin E2 EP1 receptor is responsible for NMDA excitotoxicity in the brain after injury. Consequently, in this study, we investigated the use of SC-51089, a selective prostaglandin E2 EP1 receptor antagonist, as a pre-treatment modality to decrease cell death, reduce brain edema, and improve neurobehavioral function after surgically induced brain injury (SBI) in mice. Eleven-week-old C57 black mice (n=82) were randomly assigned to four groups: sham (n=31), SBI (n=27), SBI treated with SC51089 at 10 μg/kg (n=7), and SBI treated with SC51089 at 100 μg/kg (n=17). Treated groups received a single dose of SC51089 intrapertioneally at 12 and 1 h pre-surgery. SBI was performed by resecting the right frontal lobe using a frontal craniotomy. Postoperative assessment occurred at 24 and 72 h, and included neurobehavioral testing and measurement of brain water content and cell death. Results indicated that neither low- nor high-dose EP1 receptor inhibition protected against the SBI-related effects on brain edema formation or cell death. There was however a significant improvement in neurobehavioral function 24 h post-SBI with both dosing regimens. Further studies will be needed to assess the potential therapeutic role of EP1 receptor targeting in SBI.

• Authors: Nikan H Khatibi, Vikram Jadhav, Brenden Matus, Nancy Fathali, Robert Martin, Richard Applegate, Jiping Tang, John H Zhang
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 111 Pg. 277-81 ( 2011) ISSN: 0065-1419 [Print] Austria
• PMID: 21725768 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Hydrazines
• Neuroprotective Agents
• Oxazepines
• Receptors, Prostaglandin E, EP1 Subtype
• SC 51089

Topics

• Animals
• Brain Edema (etiology, prevention & control)
• Brain Injuries (etiology, prevention & control)
• Cell Death (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Functional Laterality
• Hydrazines (therapeutic use)
• Male
• Mice
• Nervous System Diseases (etiology, prevention & control)
• Neuroprotective Agents (therapeutic use)
• Neurosurgical Procedures (adverse effects)
• Oxazepines (therapeutic use)
• Receptors, Prostaglandin E, EP1 Subtype (antagonists & inhibitors)
• Time Factors
• Treatment Failure