Tim Lekic1, Damon Klebe1, Devin W McBride1, Anatol Manaenko1, William B Rolland1, Jerry J Flores1, Orhan Altay1, Jiping Tang1, John H Zhang2. 1. From the Departments of Physiology and Pharmacology (T.L., D.K., D.W.M., A.M., W.B.R., J.J.F., O.A., J.T., J.H.Z.), Neurology (T.L.), and Neurosurgery (J.H.Z.), Loma Linda University School of Medicine, CA. 2. From the Departments of Physiology and Pharmacology (T.L., D.K., D.W.M., A.M., W.B.R., J.J.F., O.A., J.T., J.H.Z.), Neurology (T.L.), and Neurosurgery (J.H.Z.), Loma Linda University School of Medicine, CA. johnzhang3910@yahoo.com.
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.
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.
Authors: Tim Lekic; Anatol Manaenko; William Rolland; Paul R Krafft; Regina Peters; Richard E Hartman; Orhan Altay; Jiping Tang; John H Zhang Journal: Exp Neurol Date: 2012-04-15 Impact factor: 5.330
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Authors: Damon Klebe; Jerry J Flores; Devin W McBride; Paul R Krafft; William B Rolland; Tim Lekic; John H Zhang Journal: J Cereb Blood Flow Metab Date: 2016-12-20 Impact factor: 6.200
Authors: Damon Klebe; Devin McBride; Paul R Krafft; Jerry J Flores; Jiping Tang; John H Zhang Journal: J Neurosci Res Date: 2019-02-21 Impact factor: 4.164
Authors: William B Rolland; Paul R Krafft; Tim Lekic; Damon Klebe; Julia LeGrand; Abby Jones Weldon; Liang Xu; John H Zhang Journal: J Neurochem Date: 2017-02-02 Impact factor: 5.372