Taurine improves functional and histological outcomes and reduces inflammation in traumatic brain injury
Introduction
Traumatic brain injury (TBI) is a major cause of death and disability. It is associated with a complex sequence of inflammatory responses characterized by glial activation, neutrophil and macrophage recruitment, upregulation of adhesion molecules, and secretion of cytokines (Werner and Engelhard, 2007, Lotocki et al., 2009). Brain injury shows the pathophysiology of inflammation including diffuse brain edema and neurological functional deficits. In addition, TBI elicits reactive astrogliosis reflecting the degree of brain injury (Laird et al., 2008).
Clinical and experimental TBI is associated with altered systemic and brain levels of cytokines including interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) (Morganti-Kossman et al., 1997, Maier et al., 2001, Ziebell and Morganti-Kossmann, 2010). Recently, a novel Luminex assay was used to detect 23 cytokines in the cerebral cortex of rats at 3 h and 24 h following a moderate fluid percussion injury (mFPI). The results indicated mFPI significantly elevated levels of IL-1α, IL-6, growth-related oncogene (GRO/KC, systemic name: CXCL1); Macrophage inflammatory protein-1α (MIP-1α), and TNF-α in the cortex, but decreased levels of IL-4, IL-12, IL-13, IL-17 and IL-18 (Redell et al., 2013). Luminex is currently the most widely used multiplex biomarker analysis technology with distinct advantages of higher throughput, and smaller sample volume. It consumes less time and is associated with lower cost compared with enzyme-linked immunosorbent assay (ELISA). This method enables a more complete assessment of the cytokine cascade that occurs following TBI. It has also been used for the detection of cytokines in the cerebrospinal fluid (CSF) and serum of patients after TBI (Buttram et al., 2007, Hergenroeder et al., 2010).
Taurine (Tau), 2-aminoethane sulfonic acid, acts as an osmoregulator (Schaffer et al., 2000), neuromodulator, calcium regulator (El Idrissi, 2008), antioxidant (Messina and Dawson, 2000), and provides neuroprotection against excitotoxic cell death (Huxtable, 1989). It has been associated with potent anti-inflammatory effects in a variety of models of systemic inflammation, including the spinal cord injury (SCI) (Nakajima et al., 2010), ischemic stroke (Sun et al., 2012), hepatic ischemia reperfusion (Zhang et al., 2010), and lung injury (Abdih et al., 2000). Specifically, taurine has been shown to diminish the production of cytokines, such as IL-1β, IL-6 and TNF-α in SCI and risk of ischemic stroke (Nakajima et al., 2010, Sun et al., 2012). Therefore, we hypothesized that taurine may attenuate TBI-induced inflammatory response.
Our aim was to investigate the interaction of taurine with the cascade of inflammation in a rat model of TBI using Luminex technology. We also examined the impact of taurine in cerebral edema, astrocyte activity and neurological function after TBI.
Section snippets
Animals
Adult male Sprague–Dawley rats, weighing between 260 and 300 g and obtained from the Experimental Animal Laboratories of the Academy of Military Medical Sciences (Beijing, China) were used for all experiments. Animal care was in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (Institute for Laboratory Animal Research, the National Academy of Sciences, Washington, DC, USA). Rats were housed under standard conditions of temperature (23 ± 2 °C) and
Neurological score
Fig. 2 shows the changes of sensorimotor function in rats after different treatments. The TBI group showed significant functional deficits at 1, 3, 5 and 7 days after TBI, compared with the sham group. In addition, the Tau group showed a significantly lower score than the TBI group at 3, 5 and 7 days after TBI (p < 0.05), however, still at levels that were significantly higher than the sham group (p < 0.05).
Cerebral water content
Changes in the cerebral water content of the rats are shown in Fig. 3. TBI caused a
Discussion
In comparison with the sham group (control), animals with TBI exhibited a higher count of certain cytokines/chemokines and water content, increased accumulation of reactive astrogliosis in the ipsilateral brain, with evidence of neurological functional deficits. In clinical experiences there are at least three types of TBI, which included mild, moderate and severe types. Cortical injury, brain edema, reactive astrogliosis as well as neurological deficits were found in the present study, which
Conclusion
In summary, we conclude that taurine reduced the expression of inflammatory cytokines, reactive astrogliosis, cerebral edema and improved neurological function following TBI. Further investigations are needed in multiple brain regions and at multiple time-points after injury to determine the underlying mechanisms of action and interaction with cytokines.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (30973089), Tianjin Research Program of Application Foundation and Advanced Technology (10JCYBJC12200) and fund project of Tianjin Municipal Health Bureau of Science and Technology (2012KR09).
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These two authors contributed equally.