A head injury such as a concussion can lead to depression later on, a new animal study suggests.
Ohio State researchers found that head injuries cause immune-system brain cells to go on "high alert" and overreact to later immune challenges by becoming excessively inflammatory - a condition linked with depressive complications, according to a press release.
They found that in mice, high alert cells in the brain had an exaggerated response to an immune challenge one month after a moderate brain injury. The increased brain inflammation was consistent with the development of depressive behaviors that were not observed in uninjured mice.
"A lot of people with a history of head injury don't develop mental-health problems until they're in their 40s, 50s or 60s," lead author Jonathan Godbout, associate professor of neuroscience at The Ohio State University and a researcher in the Institute for Behavioral Medicine Research, said in a statement. "That suggests there are other factors involved, and that's why we are looking at this two-hit idea - the brain injury being the first and then an immune challenge. It's as if one plus one plus one equals 15. There can be a multiplier effect."
Researchers findings could help explain some of the mid-life mental-health issues suffered by individuals who experience multiple concussions as young adults. And the depressive symptoms are likely inflammation-related, which means they may not respond to common antidepressants.
In the study, researchers compared uninjured mice with mice that had experienced a moderate TBI. Injured mice showed some initial coordination problems, but those resolved within a week.
The injured mice also showed signs of depressive symptoms that improved within one month. Godbout and colleagues attributed those symptoms to the expected neuroinflammation that occurs after a traumatic brain injury. In these mice, most of the inflammation cleared within seven days.
"The young adult mice that have a diffuse head injury basically recover to normal, but not everything is normal," Godbout said. "The brain still has a more inflammatory makeup that is permissive to hyperactivation of an immune response."
Thirty days after sustaining a head injury, the mice were injected with lipopolysaccharide - "the dead, outer cell wall of bacteria" that stimulates an immune reaction in animals. Researchers found that over the course of 24 hours after the injection, TBI mice were much less social than uninjured mice -- one type of depressive symptom in the animals. The brains of the TBI mice also had dramatically higher levels of two inflammation-related proteins than did brains from normal mice.
According to a press release, 72 hours after the challenge, injured mice showed additional depressive symptoms, including minimal interest in sugar water -- a sign that they avoided what is typically a pleasurable activity. They also showed increased resignation, or a sign of "giving up."
"If we had waited three, six or nine months, the symptoms probably would have gotten even worse," Godbout said.
In a press release, researchers said an added complication to someone who has suffered concussion as a younger adult is that aging already increases brain inflammation.
"So on top of normal aging concerns, people who have had a traumatic brain injury experience added inflammation caused by magnified immune responses to so-called 'secondary challenges,' such as a second head injury, infections or other stressors," researchers said in a statement.
Researchers are now investigating potential treatments that could either prevent the priming of microglia immediately after injury or later reverse the high-alert characteristics of these cells.
