Accession Number:

ADA630250

Title:

Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

Descriptive Note:

Journal article

Corporate Author:

ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX

Report Date:

2010-04-09

Pagination or Media Count:

14.0

Abstract:

Background Activated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor DAF, also known as CD55 inhibits complement activation by suppressing the function of C3C5 convertases, thereby limiting local generation or deposition of C3aC5a and membrane attack complex MAC or C5b-9 production. The present study investigates the ability of DAF to protect pr imary cultured neuronal cells subjected to sodium cyanide NaCN-induced hypoxia from degeneration and apoptosis. Methods Cultured primary cortical neurons from embryonic Spra gue-Dawley rats were assigned one of four groups control, DAF treatment alone, hypoxic, or hypoxic treated with DAF. Hypoxic cultures were exposed to NaCN for 1 hour, rinsed, followed by 24 hour exposure to 200 ngml of recombinant human DAF in normal medium. Human DAF was used in the present study and it has been shown to effectiv ely regulate complement activation in rats. Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. Complement C3, C3a, C3a receptor R production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src. Results When compared to controls, hypoxic cells had fewer dendritic spines , reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE