Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures

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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. K E Y W O R D Sastrocytes, astrogliosis, attention, behavior, brain, cerebral cortex, cognitive impairment, GFAP, gray matter, mammals, memory, neuroinflammation, reactive microglia, TBI (traumatic brain injury), white matter

Section: Morphologic Changes Of Microglial Reactivity In White Mattersupporting

confidence: 92%

Section: Novel Object Recognitionmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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

Schwerin

Chatterjee

Imam-Fulani

et al. 2018

Self Cite

Unconventional animal models for traumatic brain injury and chronic traumatic encephalopathy

Ackermans

Varghese

Wicinski

et al. 2021

A strike to the head: Parallels between the pediatric and adult human and the rodent in traumatic brain injury

Smith,

Grayson

2024

Traumatic brain injury (TBI) is a condition that occurs commonly in children from infancy through adolescence and is a global health concern. Pediatric TBI presents with a bimodal age distribution, with very young children (0–4 years) and adolescents (15–19 years) more commonly injured. Because children's brains are still developing, there is increased vulnerability to the effects of head trauma, which results in entirely different patterns of injury than in adults. Pediatric TBI has a profound and lasting impact on a child's development and quality of life, resulting in long‐lasting consequences to physical, cognitive, and emotional development. Chronic issues like learning disabilities, behavioral problems, and emotional disturbances can develop. Early intervention and ongoing support are critical for minimizing these long‐term deficits. Many animal models of TBI exist, and each varies significantly, displaying different characteristics of clinical TBI. The neurodevelopment differs in the rodent from the human in timing and effect, so TBI outcomes in the juvenile rodent can thus vary from the human child. The current review compares findings from preclinical TBI work in juvenile and adult rodents to clinical TBI research in pediatric and adult humans. We focus on the four brain regions most affected by TBI: the prefrontal cortex, corpus callosum, hippocampus, and hypothalamus. Each has its unique developmental projections and thus is impacted by TBI differently. This review aims to compare the healthy neurodevelopment of these four brain regions in humans to the developmental processes in rodents.