Juvenile concussions in mice linked to progressive changes in the brain later in life
By Emily Sugg. This article was initially published in the 10/23/25 edition of our Concussion Update newsletter; please consider subscribing.
A groundbreaking new study published in Experimental Neurology found that a single juvenile concussion in male mice led to progressive changes in white matter across their lifespan. This study, led by Andre Obenaus, observed changes in the brain structure of three groups of juvenile mice at 1, 3, 6, 12, and 18 months after experiencing a “mild” concussion, a “severe” concussion, or no concussion (for a control group). The researchers used neuroimaging to track changes in the corpus callosum, the largest white matter structure in the brain. Their results suggest that “long-term monitoring of children with juvenile concussive episodes using dMRI is warranted” to keep an eye on vulnerable tracts of white matter.
The researchers randomly assigned the mice to three groups (sham group, grade 1 concussion group, grade 2 concussion group). Grade 1 concussion group (G1) was put under anesthesia and received an impact to their head at around 2 m/s. To simulate the variation in the nature of concussions humans experience, they also created a grade 2 concussion group. The mice in this group received a slightly faster impact at 3 m/s, creating a more “severe” concussion than grade 1. The sham group was put under anesthesia, like the other groups, but did not receive any impact, as they would use this group to control variables.
Obenaus and his colleagues looked for changes in brain structure at 1, 3, 6, 12, and 18 months post brain injury using diffusion MRI (dMRI) to create detailed images of brain tissue and the effects on white matter tracts in the brain. Mice in group G2, which received a more severe concussion, showed dramatic changes in the corpus callosum structure after just 3 months post-concussion compared to G1 mice, where researchers first saw changes at 12 months. These changes persisted (and, in the case of some measures, worsened) throughout the 18-month study window, indicative of persisting axonal damage. The corpus callosum is the main communication highway for both hemispheres and is critical for motor skills, sensory processing, and cognition.
After 18 months, they used post-mortem immunohistochemistry (IHC), analyzing brain tissue samples taken after death. Scientists use this method to understand and specifically identify the causes of brain damage. Compared to the control group, the mice that experienced a grade 2 concussion showed signs of chronic inflammation and structural alterations in their brain cells. Specifically, the researchers found differences in two types of brain cells: astrocytes and microglia. Astrocytes help maintain stability in the brain by regulating the blood-brain barrier, removing waste and excess ions, regulating cerebral blood flow, and transporting nutrients to neurons. Microglia are part of the immune system and “regulate brain development, maintenance of neuronal networks, and injury repair” through promoting inflammatory responses in the brain after injury. Using IHC, the researchers observed that the astrocytes in the grade 2 concussion group had less complex shapes than those in the control group, while microglia showed hyperactivation (indicating a dysregulated and persisting inflammatory response to injury). These abnormalities offer a potential explanation for the observed progressive white matter damage.
Dr. Andre Obenaus and his team found that childhood concussion does, in fact, create vulnerability later in life in juvenile mice. In an article for University of California, Riverside News by Iqbal Pittalwala, Obenaus draws parallels between the persisting structural injury seen in this mouse study and increasing evidence of persisting changes in the brain following concussions in humans. Dr. Obenaus reinforces these observations in the article, stating, “‘Children who experience a concussion should not be declared ‘fully recovered’ based only on short-term symptoms. Subtle changes may take years to show up and, by then, interventions may be more difficult.’”