Progression of histopathological and behavioral abnormalities following mild traumatic brain injury in the male ferret

• Published in: Journal of neuroscience research Vol. 96; no. 4; pp. 556 - 572
• Main Authors: Schwerin, Susan C., Chatterjee, Mitali, Imam‐Fulani, Aminat O., Radomski, Kryslaine L., Hutchinson, Elizabeth B., Pierpaoli, Carlo M., Juliano, Sharon L.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2018
• Subjects: Abnormalities; Astrocytes; astrogliosis; attention; Attention Deficit Hyperactivity Disorder; Behavior; Brain; Brain damage; Cerebral cortex; Cognition & reasoning; Cognitive ability; cognitive impairment; Cortex (somatosensory); Gait; GFAP; gray matter; Head injuries; Human behavior; Immunohistochemistry; Inflammation; mammals; Memory; Microglia; Microglial cells; Mustelidae; neuroinflammation; Object recognition; Open-field behavior; Pattern recognition; reactive microglia; Rodents; Substantia alba; TBI (traumatic brain injury); Traumatic brain injury; white matter; memory; reactive microglia; TBI (traumatic brain injury); astrogliosis; brain; GFAP; cerebral cortex; white matter; mammals; neuroinflammation; gray matter; attention; cognitive impairment; astrocytes; behavior
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.24218

White matter damage is an important consequence of traumatic brain injury (TBI) in humans. Unlike rodents, ferrets have a substantial amount of white matter and a gyrencephalic brain; therefore, they may represent an ideal small mammal model to study human‐pertinent consequences of TBI. Here we report immunohistochemical and behavioral results after a controlled cortical impact (CCI) injury to the sensorimotor cortex of adult male ferrets. We assessed inflammation in the neocortex and white matter, and behavior at 1 day post injury and 1, 4, and 16 weeks post injury (WPI). CCI in the ferret produced inflammation that originated in the neocortex near the site of the injury and progressed deep into the white matter with time. The density of microglia and astrocytes increased in the neocortex near the injury, peaking at 4WPI and remaining elevated at 16WPI. Microglial morphology in the neocortex was significantly altered in the first 4 weeks, but showed a return toward normal at 16 weeks. Clusters of microglial cells in the white matter persisted until 16WPI. We assessed motor and cognitive behavior using the open field, novel object recognition, T‐maze, and gait tests. A transient deficit in memory occurred at 4WPI, with a reduction of rearing and motor ability at 12 and 16WPI. Behavioral impairments coincide with features of the inflammatory changes in the neocortex revealed by immunohistochemistry. The ferret represents an important animal model to explore ongoing damage in the white matter and cerebral cortex after TBI. Microglia in the ferret cerebral cortex become activated after TBI and increase in density, but return to control levels by 16 weeks post injury. In the underlying white matter, IBA1‐labeled cells form clusters and surround blood vessels (yellow arrows) at 4WPI and continue doing so until at least 16WPI.