Combined fluid percussion brain injury and entorhinal cortical lesion: A model for assessing the interaction between neuroexcitation and deafferentation

L. L. Phillips, Bruce G Lyeth, R. J. Hamm, J. T. Povlishock

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Laboratory studies suggest that excessive neuroexcitation and deafferentation contribute to long-term morbidity following human head injury. Because no current animal model of traumatic brain injury (TBI) has been shown to combine excessive neuroexcitation and significant levels of deafferentation, we developed a rat model combining the neuroexcitation of fluid percussion TBI with subsequent entorhinal cortical (EC) deafferentation. In this paradigm, moderate fluid percussion TBI was induced in each rat, followed 24 h later by bilateral EC lesion (BEC). Six conditions were examined: (1) fluid percussion TBI followed 24 h later by bilateral EC lesion (TBEC), (2) fluid percussion TBI (TBI), (3) bilateral EC lesion (BEC), (4) sham fluid percussion TBI (SHAM), (5) TBI followed 24 h later by unilateral EC lesion (TUEC), and (6) unilateral EC lesion (UEC). The first four groups were assessed for motor (with beam-balance and beam-walk testing) and cognitive deficits (with the Morris water maze) and hippocampal morphology (with immunocytochemistry and electron microscopy). The TUEC and UEC groups were assessed for cognitive deficits alone. Motor deficits were greater in the TBEC injury than in TBI or sham alone; however, no significant difference was observed between the TBEC and BEC conditions in motor performance. Cognitive deficits were of a greater magnitude in the combined TBEC injury model relative to each individual insult. These cognitive deficits appeared to be additive for the two experimental injuries, BEC deafferentation producing deficits intermediate between TBI and TBEC insults. Morphologic analysis of the dentate gyrus molecular layer at 15 days after TBEC showed that the distribution of synaptophysin-positive presynaptic terminals was distinct from that observed after either TBI or BEC alone. Specifically, the laminar pattern of presynaptic rearrangement induced by BEC lesion did not occur after TBEC injury. The present results show that axonal injury and its attendant deafferentation, when coupled with traumatically induced neuroexcitation, produce an enhancement of the morbidity associated with TBI. Moreover, they indicate that this model can effectively be used to study the interaction between neuroexcitation and synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)641-656
Number of pages16
JournalJournal of Neurotrauma
Issue number6
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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