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

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. D...

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Bibliographic Details
Main Authors: Wang, Ying, Li, Yansong, Dalle Lucca, Shawn L, Simovic, Milomir, Tsokos, George C, Dalle Lucca, Jurandir J
Format: Report
Language:English
Subjects:
ACTIVATION
AGING(PHYSIOLOGY)
Anatomy and Physiology
APOPTOSIS
ASSAYING
CAF(DECAY-ACCELERATING FACTOR)
CEREBRAL CORTEX
CYANIDES
DECAY
DEGENERATION(PHYSIOLOGY)
ELECTROPHYSIOLOGY
EMBRYOS
HYPOXIA
INFLAMMATION
INHIBITION
ISCHEMIA
Medicine and Medical Research
NERVE CELLS
NEUROINFLAMMATION
NEUROLOGY
NEURONAL CELL DEATH
NEURONAL CELLS
RATS
RECEPTOR SITES(PHYSIOLOGY)
REPERFUSION INJURIES
RESPONSE(BIOLOGY)
SPINAL COLUMN
STATISTICAL ANALYSIS
THERAPY
TISSUES(BIOLOGY)
TRAUMATIC BRAIN INJURIES
VIABILITY
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Summary: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 C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a 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 ng/ml 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. Published in the Journal of Neuroinflammation, v7 n24 p1-13, 9 April 2010. Sponsored in part by the DoD.