title: Midline brain injury in the immature rat induces sustained cognitive deficits, bihemispheric axonal injury and neurodegeneration.
abstract: Infants and children less than 4 years old suffer chronic cognitive deficits following mild, moderate or severe diffuse traumatic brain injury (TBI). It has been suggested that the underlying neuropathologic basis for behavioral deficits following severe TBI is acute brain swelling, subarachnoid hemorrhage and axonal injury. To better understand mechanisms of cognitive dysfunction in mild-moderate TBI, a closed head injury model of midline TBI in the immature rat was developed. Following an impact over the midline suture of the intact skull, 17-day-old rats exhibited short apnea times (3-15 s), did not require ventilatory support and suffered no mortality, suggestive of mild TBI. Compared to un-injured rats, brain-injured rats exhibited significant learning deficits over the first week post-injury (p<0.0005), and, significant learning (p<0.005) and memory deficits (p<0.05) in the third post-injury week. Between 6 and 72 h, blood-brain barrier breakdown, extensive traumatic axonal injury in the subcortical white matter and thalamus, and focal areas of neurodegeneration in the cortex and hippocampus were observed in both hemispheres of the injured brain. At 8 to 18 days post-injury, reactive astrocytosis in the cortex, axonal degeneration in the subcortical white matter tracts, and degeneration of neuronal cell bodies and processes in the thalamus of both hemispheres were observed; however, cortical volumes were not different between un-injured and injured rat brains. These data suggest that diffuse TBI in the immature rat can lead to ongoing degeneration of both cell soma and axonal compartments of neurons, which may contribute, in part, to the observed sustained cognitive deficits.
authors.affiliation: Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Jimmy W
authors.initials: JW
authors.lastname: Huh
authors.forename: Ashley G
authors.initials: AG
authors.lastname: Widing
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghupathi
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007839:Functional Laterality; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009474:Neurons / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*