Males and females respond to head hits differently
CHICAGO — Large numbers of kids play sports that can result in an accidental bump to the head. If the blow is hard enough, a concussion — brain injury — may occur. But symptoms and the time it takes to recover can differ depending on whether the patient is male or female, a new study in mice shows.
It’s important to figure out how males and females might be different after injury, says Carmen Lin. She’s a neuroscientist at Northwestern University in Evanston, Ill. Determining how the sexes differ after concussion might even help scientists tailor better treatments for each, she notes.
When playing the same sport, girls are as likely to suffer from a concussion as are boys, notes Ramesh Raghupathi. He works at Drexel University in Philadelphia, Pa. As a neuroscientist, he studies how the brain functions. He noticed that a lot of brain-injury research looked at effects only in males. Scientists had assumed females would respond similarly.
But Raghupathi wasn’t so sure. “The best way to address this is to face it head on,” he says. So his team decided to give mild concussions to male and female adolescent mice. They then watched what happened over the next two months.
When a person gets a hard blow to the head, she might experience dizziness, nausea and memory problems. But even after these symptoms fade, headaches and a persistent feeling of sadness, known as depression, might continue. So the scientists decided to look for similar effects in their mice.
They couldn’t ask a mouse directly if it was feeling depressed, however. But they could look for signs of that in how it swam.
When a mouse realizes it can’t escape a pool, it eventually gives up and floats. Biologists interpret this as being similar to depression. The behavior serves as an animal model for that condition in people. One to two months after a concussion, male mice quickly gave up and floated. Females, however, kept swimming. This suggests that after brain injury, human men and boys also might be more prone to depression for months afterward, Raghupathi says.
The female mice appeared to suffer in a different way. They became more sensitive to touch. In rodents, this sensitivity “is a marker of headache,” Raghupathi explains. And not just any type of headache, but a serious type called a migraine “When you suffer from a migraine you are sensitive to light and touch,” he notes.
To investigate this condition in their animals, the scientists gently touched the face of a mouse with very thin wires. It doesn’t hurt the animal. But when the mouse feels the touch, it will turn its head or brush the wire away with a paw. Females were much more sensitive to these wires, long after they had been injured. This could mean human women and girls would be more susceptible than males to a persistent risk of migraines following concussions, Raghupathi concludes.
Probing the chemistry
Finally, Raghupathi and his laboratory focused on the brain’s production of a chemical called dopamine (DOE-pah-meen). It carries important messages between brain cells. Dopamine is very important for executive function. These are tasks that require self-control and motivation. This chemical also is important in depression.
The scientists used fibers to measure the amount of dopamine in the animals’ brains. They measured it in the nucleus accumbens, a region linked to motivation. At first, they saw no difference. Then, the researchers added some cocaine. This drug acts as a stimulant, giving users powerful feelings of pleasure and energy. Even though cocaine is a highly addictive drug, scientists can use its properties to probe how parts of the brain work.
Usually, cells in the brain slurp up dopamine after it has been used and then recycle the chemical. In theory, our cells can use it over and over. But cocaine stops this from happening. Instead dopamine builds up between cells. This causes that feeling that drug users describe as a “high.” But it also prevents the brain from reusing much of that dopamine for quite a while.
When the researchers added cocaine to injured mouse brains, they found that male mice with concussions had more dopamine building up in between cells than did females or non-injured mice. This stronger male response to cocaine suggested that they had a reduced ability to recycle the dopamine in their brains.
“Dopamine controls motivation,” Raghupathi says. If the male mice can’t recycle their dopamine as well, this might explain why they show behaviors resembling depression, he argues. He presented his team’s findings October 19 here at the Society for Neuroscience annual meeting.
The concussions that Raghupathi’s group gave to the mice were designed to be very mild. But males still showed effects suggestive of depression as much as two months after their injuries. Females showed an exaggerated sensitivity to touch for just as long.
Impacts from concussions also may linger, Raghupathi now worries. That may happen “even if you feel normal, even if you return to play,” he says. “Your brain is still impaired.”
If what he saw in mice also occurs in people, teens with concussions might even be more vulnerable to stress from tests, social life or other daily woes, he says.
Next, Raghupathi wants to investigate how more than one concussion might affect the brain. “The reality,” he says, “is people go back to play.” Data have shown that people who have had one concussion are more likely to have a second or third, he points out.
He wants to find out if the effects get worse with each additional bang to the brain. He is also curious whether the impacts differ in males and females. The findings, he hopes, might lead to treatments that let players get back on the field with their brains and behaviors intact.
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addiction The uncontrolled use of a habit-forming drug or uncontrolled and unhealthy habit (such as video game playing or phone texting). It results from an illness triggered by brain changes that occur after using some drugs or engaging in some extremely pleasurable activities. People with an addiction will feel a compelling need to use a drug (which can be alcohol, the nicotine in tobacco, a prescription drug or an illegal chemical such as cocaine or heroin), even when the user knows that doing so risks severe health or legal consequences.
animal model A nonhuman animal used to stand in for people in research testing. Which animal a lab uses will depend on how closely parts of its body or chemical-signaling systems match those in people.
chemical A substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.
concussion Temporary unconsciousness, or headache, dizziness or forgetfulness due to a severe blow to the head.
depression A mental illness characterized by persistent sadness and apathy. Although these feelings can be triggered by events, such as the death of a loved one or the move to a new city, that isn’t typically considered an “illness” — unless the symptoms are prolonged and harm an individual’s ability to perform normal daily tasks (such as working, sleeping or interacting with others). People suffering from depression often feel they lack the energy needed to get anything done. They may have difficulty concentrating on things or showing an interest in normal events. Many times, these feelings seem to be triggered by nothing; they can appear out of nowhere.
dopamine A neurotransmitter, this chemical helps transmit signals in the brain.
executive function The term that includes all of the brain functions needed for self-regulation, self-control and problem-solving. Executive function requires good working memory to hold several pieces of information in the brain at once. It also includes multi-tasking, prioritizing, reasoning, focus, concentration, goal setting and controlling impulses.
migraine An intense headache that is often accompanied by nausea and vision changes. It typically only affects one side of the head at one time.
neuroscience Science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.
nucleus accumbens An area deep within the front part of the brain that is linked to pleasure and motivation.
stimulant Something that triggers an action. (in medicine) Drugs that can stimulate the brain, triggering a feeling of more energy and alertness. Caffeine is a mild stimulant that for a short while enhances alertness and helps fight drowsiness. Other stimulants, including some dangerous illegal drugs — such as cocaine — have stronger or longer-lasting effects.
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Original Journal Source: S. Eckert et al. Sex-dependent changes in depression and facial allodynia in the chronic period following mild TBI in the mouse. Society for Neuroscience annual meeting. Chicago, Ill. October 19, 2015.