Citation

Cole JT, Yarnell A, Kean WS, Gold E, Lewis B, Ren M, McMullen DC, Jacobowitz DM, Pollard HB, O'Neill JT, Grunberg NE, Dalgard CL, Frank JA, Watson WD. J. Neurotrauma 2011; 28(3): 359-369.

Affiliation

Uniformed Services University of the Health Sciences, Neurology, B-3012, Jones Bridge Road, Bethesda, Maryland, United States, 20814, 301-295-9792, 301-295-3825; jcole@usuhs.mil.

Copyright

(Copyright © 2011, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2010.1427

PMID

21190398

PMCID

PMC3057208

Abstract

BACKGROUND: Neurological dysfunction after a traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use "sham" (craniotomy alone) animals as control. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. METHODS: To test this hypothesis, thirty-eight adult female rats were assigned to one of three groups- control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. Rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. RESULTS: Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses as compared to trephine or naïve rats. Finally, of the seven tested cytokines, KC-GRO and IFN-γ show significant increases in both craniotomy models when compared to naïve rats. CONCLUSION: We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating "sham" procedures should distinguish among sham, experimentally injured, and healthy/naïve animals, to help reduce confounding factors. Keywords: traumatic brain injury, cytokines, magnetic resonance imaging, craniotomy, neurological severity scale (NSS).

Language: en