[Frontiers in Bioscience 14, 3795-3813, January 1, 2009]
Systemic inflammatory response following acute traumatic brain injury

Jia Lu1,2, Samantha Jianli Goh1, Priscilla Ying Lei Tng1, Yi Yu Deng2, Eng-Ang Ling2, Shabbir Moochhala1

1Combat Care Laboratory, Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive #09-01, Singapore 117510, 2Department of Anatomy, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore117597

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Is the brain an immune privileged organ?
4. Neuroinflammatory response in CNS
5. Systemic inflammatory response following acute traumatic brain injury
5.1. Systemic changes following acute TBI and SIRS
5.2. Hyperinflammation
5.3. Immunosuppression
5.4. Neuroimmune regulation of systemic inflammation
5.5. The HPA-axis
5.6. The sympathetic nervous system (SNS)
5.7. Effect of CARS on monocytes
5.8. Effects of acute TBI
5.9. Activation and reduction of complement
5.10. Coagulation
6. Role of mediators in systemic inflammatory response following TBI
6.1. Cytokines
6.2. Coagulation Factors
6.3. Complement components
6.4. Growth factors
6.5. Chemokines
6.6. Nitric Oxide (NO)
7. Conclusions
8. Acknowledgement
9. References

1. ABSTRACT

The early, delayed, and systemic effects of acute traumatic brain injury (TBI) are the result of inflammatory mediators which initiate systemic inflammatory response syndrome (SIRS), subsequent complement deficits and coagulopathy. Once SIRS is triggered by acute inflammation, it can detrimentally self-propagate. Systemic inflammation causes tissue damage leading to further inflammation and damage, leaving the body in a vicious cycle of hyperinflammation. Therefore, important inflammatory mediators like interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF) alpha, are targeted in compensatory anti-inflammatory response syndrome (CARS) in an attempt to control the development of SIRS. The hypothalamus-pituitary (HPA)-axis and sympathetic nervous system (SNS) efferent limbs in CARS provide negative feedback for the production of inflammatory mediators. However, in the case of acute TBI, the activation of CARS often leads to the complication of immunosuppression which may result in multi-organ dysfunction syndrome (MODS) and mortality. In light of this, the activation of the SIRS following acute TBI does not bode well. If left uncontrolled, multiple systems will be implicated making it difficult to remedy.