Experimental investigation of cerebral contusion: histopathological and immunohistochemical evaluation of dynamic cortical deformation.
We used a new approach, termed dynamic cortical deformation (DCD), to study the neuronal, vascular, and glial responses that occur in focal cerebral contusions. DCD produces experimental contusion by rapidly deforming the cerebral cortex with a transient, nonablative vacuum pulse of short duration (25 milliseconds) to mimic the circumstances of traumatic injury. A neuropathological evaluation was performed on brain tissue from adult rats sacrificed 3 days following induction of either moderate (4 psi, n = 6) or high (8 psi, n = 6) severity DCD. In all animals, DCD produced focal hemorrhagic lesions at the vacuum site without overt damage to other regions. Examination of histological sections showed localized gross tissue and neuronal loss in the cortex at the injury site, with the volume of cell loss dependent upon the mechanical loading (p < 0.001). Axonal pathology shown with neurofilament immunostaining (SMI-31 and SMI-32) was observed in the subcortical white matter inferior to the injury site and in the ipsilateral internal capsule. No axonal injury was observed in the contralateral hemisphere or in any remote regions. Glial fibrillary acidic protein (GFAP) immunostaining revealed widespread reactive astrocytosis surrounding the necrotic region in the ipsilateral cortex. This analysis confirms that rapid mechanical deformation of the cortex induces focal contusions in the absence of primary damage to remote areas 3 days following injury. Although it is suggested that massive release of neurotoxic substances from a contusion may cause damage throughout the brain, these data emphasize the importance of combined injury mechanisms, e.g. mechanical distortion and excitatory amino acid mediated damage, that underlie the complex pathology patterns observed in traumatic brain injury.
Department of Bioengineering, University of Pennsylvania, Philadelphia 19104-6392, USA.
D I
DI
Shreiber
A C
AC
Bain
D T
DT
Ross
D H
DH
Smith
T A
TA
Gennarelli
T K
TK
McIntosh
D F
DF
Meaney
D000818:Animals; D001253:Astrocytes / Q000737:chemistry; D001696:Biomechanical Phenomena; D001923:Brain Chemistry / Q000502:physiology*; D001924:Brain Concussion / Q000473:pathology* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D008297:Male; D009336:Necrosis; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins