4.6 Article

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

Journal

PLOS ONE
Volume 7, Issue 3, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0033646

Keywords

-

Funding

  1. National Institutes of Health
  2. National Institute of Neurological Disorders and Stroke [1R01NS071956-01]
  3. James and Esther King Foundation
  4. SanBio Inc.
  5. Celgene Cellular Therapeutics
  6. KM Pharmaceutical Consulting
  7. NeuralStem Inc.

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Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI.

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