Systemic effects of isolated brain injury: an experimental animal study M. J. Mirzayan*, C. Probst { , C. Krettek { , M. Samii { , H. C. Pape 1 , M. van Griensven " and A. Samii { *Department of Neurosurgery and { Department of Traumatology, Medical School Hannover, Hannover, Germany { International Neuroscience Institute Hannover, Hannover, Germany 1 Department of Orthopaedic Trauma, University of Pennsylvania, Pittsburgh, PA, USA " Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria Objective: Although various experimental works of neurotrauma research are performed, little attention has been paid to the concomitant systemic changes following isolated traumatic brain injury (TBI). Such investigations seem to be a prerequisite condition for evaluation of experimental drugs, which may diminish the secondary damage following TBI. We describe histopathologic findings of the lung, liver, spleen and kidney 96 hours following an experimental TBI. Methods: Ten male C57Bl/6 mice were subjected to a controlled cortical impact (CCI) over the left parietotemporal cortex using rounded-tip impounder for application of a standardized brain injury. Subjects were killed 96 hours following trauma. Brain, lung, liver, kidney and spleen were preserved for morphologic examinations. Results: Moderate histopathologic changes were evident in the lung and liver. The kidney and spleen seem not to be affected by the trauma regarding our examination. Conclusion: The findings of this study show that even isolated TBI can lead to a migration of immunocompetent cells to peripheral organs potentially leading to dysfunctions of peripheral organs to various extents. More attention to peripheral organs during experimental TBI research is indicated. [Neurol Res 2008; 30: 457–460] Keywords: Brain injury; controlled cortical impact; neuroprotection; mouse; trauma INTRODUCTION Traumatic brain injury (TBI) is one of the serious health care problems. The course of the treatment in TBI can be complicated by dysfunction of peripheral organs as the lung, liver or kidney. Such dysfunctions would deteriorate the prognosis and outcome, even in isolated TBI 11 . Trauma is more and more understood as a multisystemic disease, interfering with the function of multiple organs and systems, even with those not directly related to the site of the initial impact 7 . While numerous neurotrauma research works have been performed in various settings investigating intra- cranial changes, little attention has been paid to the simultaneous dysfunction of the peripheral organs following an isolated TBI 2,6,12 . In this setting, there is a clear paucity of information about possible alterations due to TBI. Growing knowledge of the systemic effects of an isolated TBI could provide a novel therapeutic approach in a prophylactic manner. To answer the question if isolated TBI affects peripheral organs, we investigated histopathologic findings of the lung, liver, spleen and kidney following an experimental TBI in the mouse. MATERIAL AND METHODS Animal care The study was approved by the local legislative committee (No. 03/672). Fifteen male C57Bl/6 mice aged 8–10 weeks with a mean weight of 23.0 ¡ 3.1 g were used for the study. All animals were handled at room temperature for 7 days before treatment. Throughout the study period, pelleted mouse chow and water were available ad libitum. The lighting was maintained on a 12 hour light/dark cycle. Anesthesia Analgetic therapy during the entire observation time was ensured by adding Metamizole (Novaminsulfonratiopharm, Ratiopharm GmbH, Ulm, Germany) to the drink water of the animals which was available ad libitum. All surgical procedures were performed under deep anesthesia with maintained spontaneous breathing. Anesthesia was induced by subcutaneous injection of Correspondence and reprint requests to: M. J. Mirzayan, MD, Department of Neurosurgery, Medical School Hannover, Carl- Neuberg-Str. 1, D-30625 Hannover, Germany. [mirzayan@hotmail. com] Accepted for publication June 2007. Drs Mirzayan and Probst contributed equally to this work. # 2008 W. S. Maney & Son Ltd Neurological Research, 2008, Volume 30, June 457 10.1179/174313208X276907