title: Modification of the cortical impact model to produce axonal injury in the rat cerebral cortex.
abstract: Diffuse axonal injury (DAI) is a form of brain injury that is characterized by morphologic changes to axons throughout the brain and brainstem. Previous biomechanical studies have shown that primary axonal dysfunction, ranging from minor electrophysiologic disturbances to immediate axotomy, can be related to the rate and level of axonal deformation. Some existing rodent head injury models display varying degrees of axonal injury in the forebrain and brainstem, but the extent of axonal damage in the forebrain has been limited to the contused hemisphere. This study examined whether opening the dura mater over the contralateral hemisphere could direct mechanical deformation across the sagittal midline and produce levels of strain sufficient to cause a more widespread, bilateral forebrain axonal injury following cortical impact. Intracranial deformation patterns produced by this modified cortical impact technique were examined using surrogate skull-brain models. Modeling results revealed that the presence of a contralateral craniotomy significantly reduced surrogate tissue herniation through the foramen magnum, allowed surrogate tissue movement across the sagittal midline, and resulted in an appreciable increase in the shear strain in the contralateral cortex during the impact. To evaluate the injury pattern produced using this novel technique, rat brains were subjected to rigid indentor impact injury of their left somatosensory motor cortex (1.5 mm indentation, 4.5-4.9 m/sec velocity, and 22 msec dwell time) and examined after a 2-7 day survival period. Neurofilament immunohistochemistry revealed numerous axonal retraction balls in the subcortical white matter and overlying deep cortical layers in the right hemisphere beneath the contralateral craniotomy. Retraction balls were not seen at these positions in normals, sham controls, or animals that received cortical impact without contralateral craniotomy and dural opening. The results from these physical modeling and animal experiments indicate that opening of the contralateral dura mater permits translation of sufficient mechanical deformation across the midline to produce a more widespread pattern of axonal injury in the forebrain, a pattern that is distinct from those produced by existing fluid percussion and cortical impact techniques.
authors.affiliation: Department of Bioengineering, University of Pennsylvania Head Injury Center, Philadelphia.
authors.forename: D F
authors.initials: DF
authors.lastname: Meaney
authors.forename: D T
authors.initials: DT
authors.lastname: Ross
authors.forename: B A
authors.initials: BA
authors.lastname: Winkelstein
authors.forename: J
authors.initials: J
authors.lastname: Brasko
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.forename: L B
authors.initials: LB
authors.lastname: Bilston
authors.forename: L E
authors.initials: LE
authors.lastname: Thibault
authors.forename: T A
authors.initials: TA
authors.lastname: Gennarelli
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002415:Cats; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D003399:Craniotomy; D004195:Disease Models, Animal; D004388:Dura Mater / Q000601:surgery; D007150:Immunohistochemistry; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D016900:Neurofilament Proteins