Table 3. Summary of the selected human studies showing the pathophysiological effects of statins after TBI.

RCT: Randomized controlled trial; TNF-α: Tumor necrosis factor α; TBI: traumatic brain injury; IL: Interleukin; GCS: Glasgow coma scale; GOS = Glasgow outcome scale; MRS = Modified Rankin scale; DRS = Disability rating scale; mTBI = Mild traumatic brain injury.

Study author & year	Study type & sample size	Purpose	Intervention	Outcome & Conclusion
Sánchez-Aguilar et al. 2013 [19]	RCT, 36	Effect of rosuvastatin on inflammatory cytokines and functional outcomes after TBI in humans	n=19 rosuvastatin 20mg orally,  n=17 placebo, day one - 10	Rosuvastatin ↓↓ TNF-α (p=0.004), -No effect on IL-1β (p>0.05), IL-6 (p=0.091), IL-10 (p=0.134), ↓↓ disability (p>0.03) Rosuvastatin has an anti-inflammatory effect and improves the outcomes after TBI
Naghibi et al. 2016 [22]	RCT, 43	Effect of simvastatin on the outcome of TBI	n=22 oral simvastatin 80mg first day then 40mg daily, n = 21 placebo (lactose)	Simvastatin ↓↓ CRP levels (p=0.042), ↑↑ GCS at discharge (p=0.004) Simvastatin plays an anti-inflammatory role and improves the neurological outcomes after TBI
Farzanegan et al. 2017 [23]	RCT, 64	Effect of atorvastatin on brain contusion volume and functional outcome after moderate and severe TBI	n=32 atorvastatin 20mg oral tablets, daily /first 10 days, n=32 placebo	No significant difference in contusion volume day three (p=0,073), day seven (p=0,082), improved functional outcome GOS (p=0,043), MRS (p=0.039), DRS (p=0.030) Atorvastatin has no beneficial effect on cerebral contusion. However, it was associated with improved functional outcomes.
Govindarajan et al. 2016 [24]	RCT, 135	Cortical thickness changes after mTBI and the effect of statins	n=59 ortho, n=71 mTBI, n=33 atorvastatin, n=38 non-treatment	↑↑ Cortical thinning, and axonal injury (p=0.01) in the non-treatment group Atorvastatin decreases the cortical thickness changes after TBI