Chapter title |
PAR-1, -4, and the mTOR Pathway Following Germinal Matrix Hemorrhage
|
---|---|
Chapter number | 38 |
Book title |
Brain Edema XVI
|
Published in |
Acta neurochirurgica Supplement, January 2016
|
DOI | 10.1007/978-3-319-18497-5_38 |
Pubmed ID | |
Book ISBNs |
978-3-31-918496-8, 978-3-31-918497-5
|
Authors |
Tim Lekic, Paul R. Krafft, Damon Klebe, Jerry Flores, William B. Rolland, Jiping Tang, John H. Zhang |
Abstract |
Germinal matrix hemorrhage (GMH) is the most common cause of neurological complications of prematurity and has lasting implications. PAR-1 and PAR-4 receptors are involved with upstream signaling pathways following brain hemorrhage in adult models of stroke, of which the mammalian target of rapamycin (mTOR) is a potential downstream mediator. Therefore, we hypothesized a role for PAR-1, -4/ mTOR signaling following GMH brain injury. Postnatal day 7 Sprague-Dawley rats were subjected to GMH through stereotactic infusion of collagenase into the right ganglionic eminence. Rodents were euthanized at 72 h (short term), or 4 weeks (long term). Short-term mTOR expression was evaluated by Western blot in the context of PAR-1 (SCH-79797) and PAR-4 (P4pal10) inhibition. Pups in the long-term group were administered the selective mTOR inhibitor (rapamycin) with neurobehavioral and brain pathological examinations performed at 4 weeks. Pharmacological PAR-1, -4 antagonism normalized the increased mTOR expression following GMH. Early inhibition of mTOR by rapamycin improved long-term outcomes in rats. Mammalian-TOR signaling plays an important role in brain injury following neonatal GMH, possibly involving upstream PAR-1, -4 mechanisms. |
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