@article{3a0c082544a047099ec7d792bd909128,
title = "P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury",
abstract = "The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI). This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, 1 day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals 8 months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI.",
author = "Yin, {Terry C.} and Britt, {Jeremiah K.} and {De Jes{\'u}s-Cort{\'e}s}, H{\'e}ctor and Yuan Lu and Genova, {Rachel M.} and Khan, {Michael Z.} and Voorhees, {Jaymie R.} and Jianqiang Shao and Katzman, {Aaron C.} and Huntington, {Paula J.} and Cassie Wassink and Latisha McDaniel and Newell, {Elizabeth A.} and Dutca, {Laura M.} and Jacinth Naidoo and Huxing Cui and Bassuk, {Alexander G.} and Harper, {Matthew M.} and McKnight, {Steven L.} and Ready, {Joseph M.} and Pieper, {Andrew A.}",
note = "Funding Information: We thank Mike Welsh and Randy Kardon for advice and encouragement and Noelle Williams for pharmacologic studies. Medical illustration was provided by Teresa A. Ruggle (Department of Internal Medicine Design Center, University of Iowa Hospitals and Clinics) and Victor Powell (Medical Media, Iowa City VA Health Care System). The work was funded by a grant awarded to A.A.P. and S.L.M. from the NIMH (5-RO1-MH087986); grant awards from the Welch Foundation (I-1612) and the Edward N. and Della C. Thome Memorial Foundation to J.M.R.; unrestricted funds provided to S.L.M. by an anonymous donor; NIH grants 1R21MH100086-01 and 5R01NS064159-05 to A.G.B.; the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (Center for the Treatment and Prevention of Visual Loss, RR&D Career Development Award [to M.M.H.] and Merit Award RX000427); and a National Science Foundation Graduate Research Fellowship to H.D.J.-C. Publisher Copyright: {\textcopyright} 2014 The Authors.",
year = "2014",
month = sep,
day = "25",
doi = "10.1016/j.celrep.2014.08.030",
language = "English (US)",
volume = "8",
pages = "1731--1740",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}