TY - JOUR
T1 - The influence of the peptide NAP on Mac-1-deficient mice following closed head injury
AU - Zaltzman, Roy
AU - Alexandrovich, Alexander
AU - Trembovler, Victoria
AU - Shohami, Esther
AU - Gozes, Illana
N1 - Funding Information:
Professor Illana Gozes is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and heads the Dr. Diana and Zelman Elton (Elbaum) Laboratory for Molecular Neuroendocrinology. These studies were supported by the Israel Science Foundation (ISF) and Allon Therapeutics, Inc. Patents have been issued and applied for NAP and it is further developed as AL-108 by Allon Therapeutics, Inc. where Professor Gozes serves as Chief Scientific Officer.
PY - 2005/8
Y1 - 2005/8
N2 - A single administration of the neuroprotective peptide NAP was previously shown to protect against death associated with closed head injury (CHI) and enhance recovery of the surviving mice. The protective effect was accompanied by down-regulation of the relative mRNA content of the complement receptor 3 (Mac-1, a marker for inflammation) as measured about a month after the injury. In contrast, the mRNA transcripts for activity-dependent neuroprotective protein (ADNP, the NAP containing protein) were shown to increase 29 days post CHI in the injured hemisphere of Mac-1 expressing mice. The present study was set out to investigate: (1) are Mac-1-deficient mice less susceptible to the adverse outcome of traumatic head injury; (2) does NAP treatment affect Mac-1-deficient mice subjected to head injury; and (3) is Mac-1 expression associated with ADNP expression. Results showed that (1) Mac-1-deficient mice were partially protected against death associated with severe head injury as compared to Mac-1 expressing mice. (2) Significant protection against death was observed in NAP-treated mice and an increase in recovery was observed in the NAP-treated Mac-1 mice 4 weeks after injury. (3) ADNP expression did not change in the Mac-1-deficient mice following head injury. Our working hypothesis is that a month following injury, gene expression in the injured brain is altered and competing proteins are expressed such as Mac-1 that is associated with inflammation and ADNP that is associated with neuroprotection. Obviously, this plasticity in gene expression is intimately interwoven with the genetic background of the animal. NAP treatment tilts the balance toward neuroprotection.
AB - A single administration of the neuroprotective peptide NAP was previously shown to protect against death associated with closed head injury (CHI) and enhance recovery of the surviving mice. The protective effect was accompanied by down-regulation of the relative mRNA content of the complement receptor 3 (Mac-1, a marker for inflammation) as measured about a month after the injury. In contrast, the mRNA transcripts for activity-dependent neuroprotective protein (ADNP, the NAP containing protein) were shown to increase 29 days post CHI in the injured hemisphere of Mac-1 expressing mice. The present study was set out to investigate: (1) are Mac-1-deficient mice less susceptible to the adverse outcome of traumatic head injury; (2) does NAP treatment affect Mac-1-deficient mice subjected to head injury; and (3) is Mac-1 expression associated with ADNP expression. Results showed that (1) Mac-1-deficient mice were partially protected against death associated with severe head injury as compared to Mac-1 expressing mice. (2) Significant protection against death was observed in NAP-treated mice and an increase in recovery was observed in the NAP-treated Mac-1 mice 4 weeks after injury. (3) ADNP expression did not change in the Mac-1-deficient mice following head injury. Our working hypothesis is that a month following injury, gene expression in the injured brain is altered and competing proteins are expressed such as Mac-1 that is associated with inflammation and ADNP that is associated with neuroprotection. Obviously, this plasticity in gene expression is intimately interwoven with the genetic background of the animal. NAP treatment tilts the balance toward neuroprotection.
KW - Activity-dependent neuroprotective protein (ADNP)
KW - Closed head injury (CHI)
KW - Mac-1
KW - NAP
KW - Neurological severity score (NSS)
UR - http://www.scopus.com/inward/record.url?scp=22544450155&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2005.03.014
DO - 10.1016/j.peptides.2005.03.014
M3 - מאמר
C2 - 16042992
AN - SCOPUS:22544450155
VL - 26
SP - 1520
EP - 1527
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 8
ER -