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Updated: Jul 10, 2026
Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury
Published on: August 14, 2019
Diffuse brain injury in the immature rat: evidence for an age-at-injury effect on cognitive function and
Ramesh Raghupathi1, Jimmy W Huh
1Department of Neurobiology and Anatomy, Drexel University College of Medicine, and Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Pennsylvania 19129, USA. rramesh@drexelmed.edu
Insights
Diffuse axonal injury in young rats (post-natal day 11) causes long-term cognitive deficits and brain atrophy. Older rats (post-natal day 17) show fewer lasting effects from similar brain trauma.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Traumatic Brain Injury Research
Background:
- Diffuse axonal injury (DAI) is a key factor in pediatric traumatic brain injury (TBI), linked to poor cognitive outcomes in children under 4.
- Immature (17-day-old) rats typically don't show cognitive deficits or gross pathology after moderate-severe diffuse brain injury.
Purpose of the Study:
- To investigate if the age of immature rats influences outcomes after moderate-severe diffuse brain injury.
- To compare behavioral and histopathological effects of non-contusive brain trauma in post-natal day 11 (PND11) versus post-natal day 17 (PND17) rats.
Main Methods:
- Non-contusive brain trauma was induced in PND11 and PND17 rats.
- Behavioral assessments included acquisition, retention (probe trial), and visual platform tasks at 28 days post-injury.
- Histopathological analysis examined cytoarchitecture, gliosis, tissue loss, and axonal injury.
Main Results:
- PND11 rats showed significant acquisition deficits, while PND17 rats did not.
- Both groups exhibited retention and visual deficits; PND17 rats had longer apnea and loss of righting reflex.
- PND11 rats developed atrophy and enlarged ventricles, with 7-10% tissue loss; PND17 rats had less pathology (3-4% tissue loss).
- Traumatic axonal injury was comparable in white matter and thalamus in both age groups.
Conclusions:
- Moderate diffuse brain injury in PND11 rats leads to chronic cognitive deficits and long-term histopathological changes.
- Age at injury is a critical factor affecting behavioral and pathological outcomes in immature rats following closed head injury.
- Younger immature rats are more vulnerable to the long-term consequences of diffuse brain injury.
Abstract:
Diffuse axonal injury is a significant component of the pathology of moderate-severe pediatric traumatic brain injury in children less than 4 years of age, and is associated with poor cognitive outcome. However, cognitive deficits or gross histopathologic abnormalities are typically not observed following moderate-severe diffuse brain injury in the immature (17-day-old) rat. In order to test whether the age of the immature animal may influence post-traumatic outcome, non-contusive brain trauma was induced in post-natal day (PND) 11 or 17 rats. Brain injury in the PND11 rat, but not in the PND17 rat, was associated with a significant acquisition deficit at 28 days post-injury (p<0.0005 compared with age-matched sham rats, and with brain-injured PND17 rats). All brain-injured animals exhibited a retention deficit in the probe trial (p<0.001), but also demonstrated a significant visual deficit in the visible platform trial (p<0.05 compared to sham animals). Although significantly longer times of apnea and loss of righting reflex were observed in brain-injured PND17 rats compared to PND11 rats (p<0.05), overt cytoarchitectural alterations and reactive gliosis were not observed in the older age group. No focal pathology was observed in the cortex below the impact site in the PND11 rat but by 28 days, the brain-injured PND11 rat exhibited atrophy in multiple brain regions and an enlarged lateral ventricle in the impact hemisphere. Quantitative analysis revealed a time-dependent increase in tissue loss in the injured hemisphere (7-10%) in the younger animals, and a modest extent of tissue loss in the older animals (3-4%). Traumatic axonal injury was observed to similar extents in the white matter and thalamus below the impact site in both brain-injured PND11 and 17 rats. These data demonstrate that non-contusive (diffuse) brain injury of moderate severity in the immature rat is associated with chronic cognitive deficits and long-term histopathologic alterations and suggest that the age-at-injury is an important parameter of behavioral and pathologic outcome following closed head injury in the immature age group.
