Complement Attacks Brain Cells After Mild Injury

A study has shown that mild injury to the brain such as that caused by brief seizures, minimal head trauma or stroke, or transient anoxia increases the susceptibility of neurons to attack and destruction by complement, which can lead to neurodegeneration and diseases such as Alzheimer's. This information was published in the October 24, 2002, issue of Neuron.

Investigators from Duke University Medical Center (Durham, NC, USA) exposed cultures of neurons and astrocytes to modest levels of glutamate, as might be generated by a mild insult to the brain. The cultures were then exposed to activated complement proteins, which selectively killed the neurons. The damage was found to be caused by the membrane attack pathway of complement. Glutamate treatment sensitized neurons, but not astrocytes, to attack by complement.

The complement immune system pathway consists of an "early activation” pathway that can be protective in Alzheimer's disease, and a "terminal” pathway, in which the proteins combine to create a "membrane attack complex.” It is the terminal pathway and the membrane attack complex that damage neurons sensitized to complement attack by mild brain insult.

"Basically, we have discovered how an insult like transient ischemic attacks, minimal drop in blood pressure, or a minimal blow to the head could facilitate the transition from the early activation pathway to the terminal membrane attack pathway, and transform a protective effect into a damaging effect on the brain,” explained senior author Dr. James O. McNamara, professor and chairman of Duke's department of neurobiology.





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