Chronic cognitive deficits and long-term histopathological alterations following contusive brain injury in the immature rat.
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.
Huh
Jimmy W
JW
Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Raghupathi
Ramesh
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D002908:Chronic Disease; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D020833:Diffuse Axonal Injury / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D016489:Head Injuries, Closed / Q000150:complications / Q000473:pathology*; D007150:Immunohistochemistry; D018782:Maze Learning; D051381:Rats