Preconditioning for Traumatic Brain Injury
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ORIGINAL ARTICLE
Preconditioning for Traumatic Brain Injury Shoji Yokobori & Anna T Mazzeo & Khadil Hosein & Shyam Gajavelli & W. Dalton Dietrich & M. Ross Bullock
Received: 25 September 2012 / Revised: 23 October 2012 / Accepted: 29 October 2012 / Published online: 15 November 2012 # Springer Science+Business Media New York 2012
Abstract Traumatic brain injury (TBI) treatment is now focused on the prevention of primary injury and reduction of secondary injury. However, no single effective treatment is available as yet for the mitigation of traumatic brain damage in humans. Both chemical and environmental stresses applied before injury have been shown to induce consequent protection against post-TBI neuronal death. This concept termed “preconditioning” is achieved by exposure to different pre-injury stressors to achieve the induction of “tolerance” to the effect of the TBI. However, the precise mechanisms underlying this “tolerance” phenomenon are not fully understood in TBI, and therefore even less information is available about possible indications in clinical TBI patients. In this review, we will summarize TBI pathophysiology, and discuss existing animal studies demonstrating the efficacy of preconditioning in diffuse and focal type of TBI. We will also review other non-TBI preconditioning studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible future clinical situations, in which pre-TBI preconditioning could be considered. S. Yokobori (*) : A. T. Mazzeo : K. Hosein : S. Gajavelli : W. D. Dietrich : M. R. Bullock Department of Neurosurgery, Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA e-mail: [email protected] S. Yokobori Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan A. T. Mazzeo Department of Anesthesia and Intensive Care, University of Turin, Turin, Italy
Keywords Preconditioning . Traumatic brain injury . Neuroprotection . Pathophysiology
Introduction A wealth of basic and clinical research exists regarding the treatment of severe traumatic brain injury (TBI). However, despite much research effort, the prognosis for severe TBI patients remains poor [1]. In the USA, an estimated 1.4 million people still suffer a TBI each year [2]. About 50,000 people die before they reach the hospital, and at least 5.3 million live with severe disabilities related to TBI [3, 4]. Worldwide, TBI is recognized as the leading cause of mortality and morbidity in young adults [5]. Globally, thus TBI stands out as a major worldwide health and socioeconomic problem [6, 7]. The most important factor which determinates the prognosis of TBI patients is the severity of the “primary” brain injury. Additional delayed “secondary” brain damage is set in progress, and continues from the time of traumatic impact in TBI patients, and the two combine to determine outcome. Primary brain injury itself is mostly not amenable to treatment; consequently
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