Repetitive Diffuse Mild Traumatic Brain Injury Causes an Atypical Astrocyte Response and Spontaneous Recurrent Seizures

Objective

Some epilepsies may be caused as a result of a traumatic brain injury. In these cases, there is often an increase in the number of a specific type of glial cell called astrocytes; this process increase is called astrogliosis. Glia are non-neuronal cells of the brain that are critical as they provide homeostasis, protection, and support. The role of astrocytes has been studied when injuries are focal; however, in humans, many head injuries are diffuse, and the role of astrocytes in these kinds of injuries isn’t well elucidated. Additionally, it is not clear whether diffuse injuries are associated with spontaneous seizures. In this study, the authors used mice to study effects of diffuse head injuries to the brain; their hypothesis was that diffuse injuries would affect the brain differently than focal injuries. A better understanding of the biology of diffuse injuries could eventually lead to progress in discovering therapies for such conditions.

Results

The authors were first able to show that diffuse head injuries led to a loss of consciousness, but no noticeable tissue damage in mice. This is in contrast to what scientists have historically seen with focal injuries. Focal head injuries cause considerable changes to astrocytes; in contrast, diffuse injury led to more subtle and diverse alterations. Diffuse injury was associated with the presence of “atypical astrocytes”, which were differentiated from typical astrocytes due of the presence of specific protein markers.

In a subset of mice, diffuse injury caused spontaneous seizures; among these, some were convulsive seizures, whereas others were not associated with convulsions. This is important because many people with head injuries may have nonconvulsive seizures, and scientists are trying to uncover the mechanisms underlying nonconvulsive seizures after brain injury.

Interpretation

The effects of head injury on the brain are complex, and not yet fully understood. Animal models provide substantial information on effects of brain injury; however, these models should ideally simulate the human condition as much as possible. Many scientists use the focal model of brain injury; this paper provides an additional model that may potentially better reflect human brain injury and its effects.

Diffuse injuries were associated with atypical astrocytes; additionally, an in-depth study of marker proteins provided a potential cellular pathway that merits future studies. In conclusion, the study shows that the effects of diffuse seizures injuries on the brain are different from focal injuries that they can be associated with seizures, and provides a cellular pathway that may serve as a potential target down the line.

Summary for specialists