Different sham procedures for rats in traumatic brain injury experiments induce corresponding increases in levels of trauma markers.

BACKGROUND In traumatic brain injury animal models, sham or naïve control groups are often used for the analysis of injured animals; however, the existence and/or significance of differences in the control groups has yet to be studied. In addition, recent controversies regarding the decompressive craniectomy trial in which decompressive craniectomies in patients with severe traumatic brain injury and refractory increased intracranial pressure remains unsettled. Although the report demonstrated that the procedure may result in less favorable long-term outcomes despite the decrease in intracranial pressure and shorter length of intensive care unit stay, the study has been criticized, and the debate is still inconclusive partly because of a lack of mechanistic explanation. We have recently discovered epithelial and endothelial tyrosine kinase (Etk) to exhibit upregulation after traumatic neural injury and will compare the effects of craniectomy procedure with those of other procedures inducing different levels of severity. MATERIALS AND METHODS Four groups of rats receiving different procedures (controlled cortical impact, craniectomy, bicortical drilling, and unicortical drilling [UD]) were compared. Polymerase chain reaction, Western blot analysis, and immunoflorescence staining of Etk, S100, and glial fibrillary acidic protein levels were used to analyze the results and compare the different groups. RESULTS Etk upregulation was statistically significant between craniectomy and UD groups. The level of change for glial fibrillary acidic protein and S100 was only significant when cortex was impacted. CONCLUSIONS UD may be preferable as a sham control procedure over craniectomy or bicortical drilling. Increases in the expression of Etk in the craniectomy group suggest a possible mechanism by which unfavorable outcome occurs in patients receiving craniectomy procedures.

[1]  A. Joussen,et al.  Differential role of tumor necrosis factor (TNF)-alpha receptors in the development of choroidal neovascularization. , 2010, Investigative ophthalmology & visual science.

[2]  H. Shih,et al.  Suppression of Etk/Bmx Protects against Ischemic Brain Injury , 2012, Cell transplantation.

[3]  E. Hall,et al.  Role of peroxynitrite in secondary oxidative damage after spinal cord injury , 2007, Journal of neurochemistry.

[4]  H. Shih,et al.  The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells , 2004, Oncogene.

[5]  R. Deane,et al.  Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. , 2010, Blood.

[6]  J. Payen,et al.  Craniectomy in diffuse traumatic brain injury. , 2011, The New England journal of medicine.

[7]  H. Shih,et al.  Location and Level of Etk Expression in Neurons Are Associated with Varied Severity of Traumatic Brain Injury , 2012, PloS one.

[8]  J. Stockman Decompressive Craniectomy in Diffuse Traumatic Brain Injury , 2012 .

[9]  K. Barbee,et al.  Mechanical membrane injury induces axonal beading through localized activation of calpain , 2009, Experimental Neurology.

[10]  E. Hall,et al.  Pharmacological evidence for a role of peroxynitrite in the pathophysiology of spinal cord injury , 2009, Experimental Neurology.

[11]  K. Alitalo,et al.  Bmx tyrosine kinase transgene induces skin hyperplasia, inflammatory angiogenesis, and accelerated wound healing. , 2004, Molecular biology of the cell.

[12]  H. Kung,et al.  A tyrosine kinase profile of prostate carcinoma. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[13]  T. Yamashima,et al.  The role of lysosomal rupture in neuronal death , 2009, Progress in Neurobiology.

[14]  J. Pickard,et al.  Microdialysis of cytokines: methodological considerations, scanning electron microscopy, and determination of relative recovery. , 2009, Journal of neurotrauma.

[15]  M. Bullock,et al.  Aquaporin-1-mediated cerebral edema following traumatic brain injury: effects of acidosis and corticosteroid administration. , 2010, Journal of neurosurgery.

[16]  N. Horwood,et al.  Bmx tyrosine kinase regulates TLR4-induced IL-6 production in human macrophages independently of p38 MAPK and NFkapp}B activity. , 2008, Blood.

[17]  Paul R. Sanberg,et al.  Severity of controlled cortical impact traumatic brain injury in rats and mice dictates degree of behavioral deficits , 2009, Brain Research.

[18]  David K Menon,et al.  Traumatic brain injury , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[19]  D. Jacobowitz,et al.  Craniotomy: true sham for traumatic brain injury, or a sham of a sham? , 2011, Journal of neurotrauma.

[20]  A. Baker,et al.  The value of serum biomarkers in prediction models of outcome after mild traumatic brain injury. , 2011, The Journal of trauma.

[21]  P. Vos,et al.  Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury , 2010, Journal of cellular and molecular medicine.

[22]  E. Hall,et al.  Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury , 2007, Experimental Neurology.

[23]  Y. Vodovotz,et al.  The Role of Fracture-Associated Soft Tissue Injury in the Induction of Systemic Inflammation and Remote Organ Dysfunction After Bilateral Femur Fracture , 2008, Journal of orthopaedic trauma.