title: 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: Department of Anesthesiology, Loma Linda Medical Center, Loma Linda, CA 92354, USA.
authors: Nikan H
authors: NH
authors: Khatibi
authors: Vikram
authors: V
authors: Jadhav
authors: Brenden
authors: B
authors: Matus
authors: Nancy
authors: N
authors: Fathali
authors: Robert
authors: R
authors: Martin
authors: Richard
authors: R
authors: Applegate
authors: Jiping
authors: J
authors: Tang
authors: John H
authors: JH
authors: Zhang
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D006834:Hydrazines / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019635:Neurosurgical Procedures / Q000009:adverse effects; D010077:Oxazepines / Q000627:therapeutic use*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D006834:Hydrazines; D018696:Neuroprotective Agents; D010077:Oxazepines; D058306:Receptors, Prostaglandin E, EP1 Subtype; C086836:SC 51089