TY - GEN
T1 - Prostaglandin E2 EP1 receptor inhibition fails to provide neuroprotection in surgically induced brain-injured mice
AU - Khatibi, Nikan H.
AU - Jadhav, Vikram
AU - Matus, Brenden
AU - Fathali, Nancy
AU - Martin, Robert
AU - Applegate, Richard
AU - Tang, Jiping
AU - Zhang, John H.
N1 - Funding Information:
Acknowledgement This study is partially supported by NIH NS053407 to J.H. Zhang and NS060936 to J. Tang. Conflict of interest statement
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - EP1 Receptor
KW - Neurosurgery
KW - SC-51089
KW - Surgically induced brain injury (SBI)
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U2 - 10.1007/978-3-7091-0693-8_46
DO - 10.1007/978-3-7091-0693-8_46
M3 - Conference contribution
C2 - 21725768
SN - 9783709106921
T3 - Acta Neurochirurgica, Supplementum
SP - 277
EP - 281
BT - Intracerebral Hemorrhage Research
PB - Springer-Verlag Wien
ER -