Therapeutic window for nonerythropoietic carbamylated-erythropoietin to improve motor function following multiple infarct ischemic strokes in New Zealand white rabbits
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Therapeutic window for nonerythropoietic carbamylated-erythropoietin to improve motor function following multiple infarct ischemic strokes in New Zealand white rabbits. / Lapchak, Paul A.; Kirkeby, Agnete; Zivin, Justin A.; Sager, Thomas N.
In: Brain Research, Vol. 1238, 31.10.2008, p. 208-214.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Therapeutic window for nonerythropoietic carbamylated-erythropoietin to improve motor function following multiple infarct ischemic strokes in New Zealand white rabbits
AU - Lapchak, Paul A.
AU - Kirkeby, Agnete
AU - Zivin, Justin A.
AU - Sager, Thomas N.
PY - 2008/10/31
Y1 - 2008/10/31
N2 - Carbamylated erythropoietin (CEPO) is a novel neuroprotective agent that does not bind to the classical erythropoietin receptor or affect hematocrit. Since CEPO has not been systematically studied in a fully blinded and randomized manner in an embolic stroke model, we determined if CEPO would be useful to attenuate clinical deficits associated with multiple infarct ischemia using the rabbit small clot embolic stroke model (RSCEM). Rabbits were embolized and treated with vehicle or CEPO within 6 h of embolization and behavioral analysis was conducted 48 h after embolization. Using quantal analysis, we determined the quantity of blood clot (mg) in brain that produce neurologic dysfunction in 50% of the rabbits (P50), with intervention considered beneficial if it increased the P50 compared to controls. CEPO administered between 5 min and 3 h after embolization significantly (p < 0.05) improved behavioral function and increased the P50 value by 55-216%. However, CEPO administration did not improve behavior when administered 6 h following embolization. In conclusion, in the RSCEM, CEPO had a therapeutic window of at least 3 h, where it effectively improved clinical rating scores and motor function. Our results suggest that CEPO may be useful to treat acute ischemic stroke and supports the study of CEPO in stroke patients.
AB - Carbamylated erythropoietin (CEPO) is a novel neuroprotective agent that does not bind to the classical erythropoietin receptor or affect hematocrit. Since CEPO has not been systematically studied in a fully blinded and randomized manner in an embolic stroke model, we determined if CEPO would be useful to attenuate clinical deficits associated with multiple infarct ischemia using the rabbit small clot embolic stroke model (RSCEM). Rabbits were embolized and treated with vehicle or CEPO within 6 h of embolization and behavioral analysis was conducted 48 h after embolization. Using quantal analysis, we determined the quantity of blood clot (mg) in brain that produce neurologic dysfunction in 50% of the rabbits (P50), with intervention considered beneficial if it increased the P50 compared to controls. CEPO administered between 5 min and 3 h after embolization significantly (p < 0.05) improved behavioral function and increased the P50 value by 55-216%. However, CEPO administration did not improve behavior when administered 6 h following embolization. In conclusion, in the RSCEM, CEPO had a therapeutic window of at least 3 h, where it effectively improved clinical rating scores and motor function. Our results suggest that CEPO may be useful to treat acute ischemic stroke and supports the study of CEPO in stroke patients.
KW - Acute ischemic stroke
KW - Behavior
KW - Clinical deficits
KW - Embolism
KW - Neuroprotection
KW - Statistical population analysis
KW - Translational science
UR - http://www.scopus.com/inward/record.url?scp=53549109121&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2008.08.017
DO - 10.1016/j.brainres.2008.08.017
M3 - Journal article
C2 - 18761001
AN - SCOPUS:53549109121
VL - 1238
SP - 208
EP - 214
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -
ID: 228506694