The influence of the peptide NAP on Mac-1-deficient mice following closed head injury.

Abstract

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.

• Authors: Roy Zaltzman, Alexander Alexandrovich, Victoria Trembovler, Esther Shohami, Illana Gozes
• Journal: Peptides (Peptides) Vol. 26 Issue 8 Pg. 1520-7 (Aug 2005) ISSN: 0196-9781 [Print] United States
• PMID: 16042992 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adnp protein, mouse
• Homeodomain Proteins
• Macrophage-1 Antigen
• Nerve Tissue Proteins
• Neuroprotective Agents
• Oligopeptides
• RNA, Messenger
• davunetide

Topics

• Animals
• Disease Models, Animal
• Head Injuries, Closed (drug therapy, physiopathology)
• Homeodomain Proteins (drug effects, genetics, metabolism)
• Macrophage-1 Antigen (genetics)
• Mice
• Mice, Knockout
• Nerve Tissue Proteins (drug effects, genetics, metabolism)
• Neurologic Examination (statistics & numerical data)
• Neuroprotective Agents (administration & dosage, therapeutic use)
• Neuropsychological Tests (statistics & numerical data)
• Oligopeptides (administration & dosage, pharmacology, therapeutic use)
• RNA, Messenger (drug effects, genetics, metabolism)
• Survival Analysis
• Time Factors