Learning how cells cross the blood-brain barrier may help with neurological diseases and injuries
Brains have a security system that is similar to that of a plane’s cockpit. Everyday cells can’t enter the control center unless they clear a careful screening process. Blood has to cross through a blood-brain barrier — the body’s equivalent of a metal detector.
Doctors and researchers believed this process kept larger cells from the immune system, which are too big and pack the kind of weapons the blood-brain barrier would filter out, from getting into the central nervous system.
The central nervous system has cells called microglia which are on active patrol, in much the same way as macrophages in the rest of the body. They are looking for potential problems that require immediate correction or attention.
In some neurological diseases, these microglia are especially prevalent and may exacerbate a problem. In other cases, however, a different type of microglia may help stabilize neurological function and signaling.
Stella Tsirka, a professor in the pharmacology department at Stony Brook University, has been studying these special cells to determine what roles they play in disease and in signaling between the immune system and the central nervous system.
Tsirka explained that her lab has divided their research into two areas. The first looks at the pathology of neuro-immune interactions. They are studying a model of stroke, multiple sclerosis and models of spinal cord injuries.
After an injury, “immune cells play an important role in maintaining or modifying the environment around the area of trauma,” she said.
The microglia are thought to be the first line of defense against injury. Later, additional peripheral immune cells infiltrate the central nervous system (when the normally secure blood-brain barrier is compromised) and modify or preserve the injured central nervous system.
At the same time, their more recent work studies the role of microglia to see how they function in the normal central nervous system (CNS).
“We’re trying to find out how neurons behave when there are microglia or not microglia present,” she offered.
Microglia may be something of a neurological stabilizer, she added, although it’s “not established yet.”
During development, microglia are thought to help in the maturation of the CNS by removing unwanted cells from neuronal terminals.
In the normal process of aging, microglia numbers increase, Tsirka observed. Exactly how they are involved in aging and potential neurological regulation with time isn’t clear yet.
Complicating matters further is that there are two different types of microglia: M1 and M2. They have opposite functions. M1 promote inflammation and cell death. M2 are anti-inflammatory and enhance cell repair and regeneration.
Treating microglia with a small beta peptide called Tuftsin has, during neuronal injury, fostered M2 properties. Using this in a model of multiple sclerosis resulted in a reduction in behavioral symptoms associated with multiple sclerosis.
So, if these microglia are relatively large and function like immune cells in the central nervous system, how did they pass through the security system that has such strict restrictions?
The key, Tsirka offered, is that they were in the pre-brain before the body constructed the security system. Indeed, a paper, which has not been verified yet, suggested that microglia migrated into the central nervous system from the human embryo’s yolk sac.
A resident of Setauket, Tsirka has worked at Stony Brook since 1992, when she came to do her postdoctoral research. She is married to Michael Frohman, the chairman of the pharmacology department. She does not report to her husband: she reports to the Dean of Research in the School of Medicine.
Their 18-year-old son Evan recently started college at Northwestern University, where he plans to blaze his own trail by studying mathematical models in social science. Their daughter Dafni, 15, entered Ward Melville in September.
Born and raised in Greece, Tsirka is the local president of the New York chapter of the American Foundation for Greek Language and Culture. Tsirka has supported the university’s efforts to build a Hellenic Studies minor and, eventually, a major.
Tsirka, who met her husband — who does not share her Greek heritage — when they lived in San Francisco, said she can relate to several elements of the movie “My Big Fat Greek Wedding.”
Despite the distance to her parents in Greece, they play an important role in her life. Every morning, she talks to them via Skype.
“If I’m not on by 7 am, my mom is worried something is wrong,” she laughed.
While her family tradition doesn’t include spraying Windex on everything (like the movie), she said family celebrations include food (although not lamb).
She also has been known around her lab for finding the Greek root of words and for sharing Greek expressions. One of her favorites: “It is not the sign of a wise man to commit the same sin twice.”