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Updated: Jul 11, 2026
Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury
Published on: January 20, 2023
Chronic cognitive deficits and long-term histopathological alterations following contusive brain injury in the
Jimmy W Huh1, Ramesh Raghupathi
1Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Insights
Pediatric contusive brain trauma in young rats causes lasting spatial learning deficits. The age of the brain-injured rat significantly impacts histopathology and cognitive outcomes.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Traumatic Brain Injury Research
Background:
- Diffuse axonal injury is primary in pediatric brain trauma, but focal contusions worsen outcomes in children under 4.
- Current pediatric brain trauma models primarily focus on diffuse injury, necessitating models for contusive injuries.
Purpose of the Study:
- To develop and characterize a rat model of contusive brain trauma in immature rats.
- To investigate the age-dependent behavioral and histopathological effects of contusive brain trauma in early development.
Main Methods:
- Closed head injury was induced using a metal-tipped indenter on the parietal cortex of postnatal day (PND) 11 and PND 17 rats.
- Spatial learning was assessed at 28 days post-injury.
- Histopathological analysis was performed at 3, 14, and 28 days post-injury.
Main Results:
- Both PND11 and PND17 rats exhibited significant spatial learning deficits post-injury.
- PND11 rats showed cortical contusions, axonal injury in white matter and thalamus, and significant atrophy by 28 days.
- PND17 rats developed a cortical cavity without evidence of diffuse axonal injury, with age-dependent reactive astrogliosis.
Conclusions:
- Contusive brain trauma in immature rats leads to chronic cognitive deficits.
- The age at the time of injury critically influences the histopathological response and long-term behavioral outcomes.
Abstract:
Although diffuse axonal injury is the primary pathology in pediatric brain trauma, the additional presence of focal contusions may contribute to the poor prognosis in brain-injured children younger than 4 years of age. Because existing models of pediatric brain trauma focus on diffuse brain injury, a model of contusive brain trauma was developed using postnatal day (PND) 11 and 17 rats, ages that are neurologically equivalent to a human infant and toddler, respectively. Closed head injury was modeled by subjecting the intact skull over the left parietal cortex of the immature rat to an impact with a metal-tipped indenter. Brain trauma on PND11 or PND17 led to significant spatial learning deficits at 28 days post-injury, compared to age-matched control rats (p < 0.05). Although both groups of rats sustained skull fractures on impact, the histopathologic response of the brain was distinctly age-dependent. At 3 days post-injury in PND11 rats, the cortex below the impact site was contused and hemorrhagic, and contained reactive astrocytes, while the subcortical white matter and thalamus contained injured (swollen) axons. At 14 and 28 days post-injury, the cortex, white matter, and hippocampus were substantially atrophied, and the lateral ventricle was enlarged. In contrast, in PND17 rats, the contused cortex observed at 3 days post-injury matured into a pronounced cavity lined with a glia limitans at 14 days; reactive astrocytes were present in both the hippocampus and thalamus up to 28 days post-injury. No evidence of traumatic axonal injury was observed in any region of the brain-injured PND17 rat. These data suggest that contusive brain trauma in the immature rat is associated with chronic cognitive deficits, but underscore the effect of the age-at-injury on behavioral and histopathologic outcomes.
