Viruses on the Brain

DISSECTING SEIZURES: Mice that suffer seizures after viral infection have a greater number of macrophages (green) in the brain.COURTESY OF ROBERT FUJINAMThe paper
M.F. Cusick et al., “Infiltrating macrophages are key to the development of seizures following virus infection,” J Virol, 87:1849-60, 2013.

The matter
Of the approximately 2.2 million Americans affected by epilepsy, a third do not respond to current antiseizure treatments, and nearly three quarters of all cases have unknown causes. Though scientists have previously linked more than 100 species of viruses that infect the central nervous system (CNS) to patients suffering from recurring seizures, the significance of viral infections in epilepsy is still unclear.

The model
Researchers at the University of Utah School of Medicine, led by Robert Fujinami, had previously developed a mouse model that suffered from seizures after infection with a CNS-targeting virus. Though the mice could clear the infection, they often continued to have seizures. To dissect how the virus might spark recurring seizures during and long after infection, Fujinami and his team took a close look at the immune responses.

The match
Fujinami’s team found that during a viral brain infection, infiltrating macrophages produce high levels of a cytokine called interleukin 6 (IL-6), which, among other cytokines, had previously been linked to seizures in the mice. To understand the importance of these IL-6–spewing macrophages, the team used a drug to block them from the CNS, which resulted in the mice having fewer seizures. Though it’s still unclear how the virus triggers seizures after the infection, Fujinami and his team suspect that macrophages continue to swarm the CNS.

The aftermath
The results suggest that “the side effect of this powerful immune response is a disruption in brain function and the ensuing brain seizures,” says Thomas M. Petro of the University of Nebraska Medical Center, who was not involved in the study.