Table 2.

Summary of preclinical studies and Main Outcomes Addressing the effect of TBI on Peripheral Metabolism

Study (year)	Experimental model/sample	Purpose	Main results
(Shahidi et al., 2018) (Shahidi et al., 2018)	Controlled cortical impact model (CCI)	investigate skeletal muscle–related changes (atrophy and degeneration/regeneration) resulting from CCI	CCI induces degeneration in Soleus and atrophy in tibialis anterior muscle.
(Ma et al., 2017b) (Ma et al., 2017b)	Controlled cerebral blast injury model	Correlation between cytokines and hepatic cytochrome P450 (CYP450) enzyme superfamily after TBI	The cytokines in serum have a negative correlation with the expressions of CYP450 enzymes.
(de Castro et al., 2017)	Fluid Percussion Injury model (FPI)	Investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training.	Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI
(Lang et al., 2015) (Lang et al., 2015)	weight drop model of TBI	Evaluate the impact of body mass index (BMI) on mortality and early neurologic outcome in patients suffering from severe TBI.	Beta-adrenergic blockade reduced TBI-induced sympathetic hyperactivity, and prevented histopathological intestinal injury, gut permeability after TBI
(Sun et al., 2015) (Sun et al., 2015)	Feeney's weight-drop method	The effects of probiotic Lactob acillus acidophilus on the intestinal smooth muscle contraction in TBI mouse model.	PKC/MLCK/MLC signaling pathway plays an important role in Lactobacillus acidophilus-mediated improvement of contractile properties of intestinal smooth muscle after TBI. .
(Villapol et al., 2015) (Villapol et al., 2015b)	Controlled cerebral blast injury model	Investigate whether systemic response to trauma is associated with the hepatic acute-phase response.	TBI induces an increase in expression of the acute-phase protein, SAA1, and also AT1R mRNA, together with several other inflammatory changes in liver.
(Anderson et al., 2015) (Anderson et al., 2015)	Cortical contusion impact (CCI) injury model.	Determine the effects of TBI alone on the gene expression of hepatic inflammatory proteins, drug-metabolizing enzymes, and transporters in CCI model	In contrast to clinical TBI, there was not a significant effect of experimental TBI on CYP or UGT27B7 metabolic enzymes.
(Zhang et al., 2014) (Zhang and Jiang, 2015a)	Fluid Percussion Injury model(FPI)	The investigate the expression of Resistin in subcutaneous adipose tissue of rats with traumatic brain injury	FPI increased the gene expression of Resistin in subcutaneous fat 12 h, 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after TBI.
(Jin et al., 2014) (Jin et al., 2014)	Fluid Percussion Injury model(FPI)	The investigate the expression of Resistin in muscle of rats after TBI	Compared with control, the muscular resistin expression in FPI increased the gene expression of Resistin in muscle
(Zhu et al., 2014) (Zhu et al., 2014)	Feeney's weight-drop method	Alterations in rat enterocyte mitochondrial respiratory function and enzyme activities in gastrointestinal after traumatic brain injury (TBI).	Rat enterocyte mitochondrial respiratory function and enzyme activities are inhibited following TBI.
(Keshavarzi et al., 2014) (Keshavarzi et al., 2014)	Controlled cerebral blast injury model	Assess the alteration of gastric function and barrier function of gastrointestinal (GI) tract following TBI.	TBI induced Inflammation, congestion, ulcer and intragastric pressure reduction
(Hu et al., 2013)(Hu et al., 2013)	Cortical contusion impact (CCI) injury model	Effect of TBI on intestinal expression pattern of CD40	The positive relationship between the expression of CD40 and that of TNF-α, VCAM-1, and ICAM-1 in jejunum after TBI.
(Olsen et al., 2013) (Olsen et al., 2013)	Controlled cortical impact injury (TBI)	Determine whether TBI affects intestinal smooth muscle function.	TBI decreased intestinal contractile activity, delayed transit that is attributed to inflammatory injury in the intestinal smooth.
(Chu et al., 2013) (Chu et al., 2013)	Controlled cortical impact injury (TBI)	The effect of TBI on molecular mechanisms in spleen and local brain inflammation.	Immediate splenectomy down-regulates the MAPKYNF-JB signaling pathway in rat brain after severe TBI.
(Larson et al., 2012) (Larson et al., 2012)	Fluid Percussion Injury model (FPI)	The effect of β-adrenergic blockade on blood pressure and left ventricle contractility after TBI	Treatment with propranolol protected against TBI-induced blood pressure, cardiac contractility and ROS generation increase.
(Zlotnik et al., 2012) (Zlotnik et al., 2012)	Controlled cortical impact injury (TBI)	The effect of nonselective β-adrenergic block antagonists on blood glutamate levels and on the neurological outcomes of rats after TBI	Systemic glutamate reduction after TBI is the result of a stress response and of the activation of the sympathetic nervous system through the β2 adrenergic receptors.
(Bansal et al., 2009) (Bansal et al., 2009b)	Weight drop TBI model	The effect of vagal nerve stimulation intestinal permeability after TBI.	The central vagal stimulation regulates intestinal permeability after TBI.
(Moinard et al., 2008) (Moinard et al., 2008)	Fluid Percussion Injury model (FPI)	The effect of TBI on liver energy homeostasis.	TBI is responsible for an impairment of liver energy homeostasis.