Table 1.

Outline of studies in which creatine or curcumin was provided prior to injury, mild traumatic brain injury, or traumatic brain injury

Study	Animal injury model	Supplementation dosing	Pathophysiological outcomes	Functional outcomes
Sullivan et al. [70]	Sprague–Dawley rats Controlled cortical impact	RD CrD 4 weeks before injury	CrD-fed rats had significantly less cortical tissue damage than RD-fed rats CrD-fed rats had significantly higher mitochondrial membrane potential than RD-fed rats CrD-fed rats had significantly fewer ROI than RD-fed rats CrD-fed rats had significantly less intramitochondrial Ca2+ than RD rats
Sullivan et al. [70]	ICR mice Controlled cortical impact	Intraperitoneal olive oil (0.1 mL·10 gBW−1 day−1) + Cr (3 mg kg− day−1) 1, 3, or 5 days prior to injury	Cr supplementation for 3 and 5 days prior to injury exhibited significantly less cortical tissue damage than Cr supplementation 1 day prior to injury and no creatine supplementation
Scheff and Dhillon [69]	Sprague–Dawley rats Controlled cortical impact	RD CrD 0.5% CrD 1.0% 2 weeks prior to injury	CrD-fed rats had significantly less cortical tissue damage than RD-fed rats but there was no significant difference between 0.5% Cr and 1% Cr
Wu et al. [73]	Sprague–Dawley rats Mild fluid percussion injury	RD (13% energy from fat) HF (39% energy from fat) RD + 500 ppm curcumin HF + 500 ppm curcumin	Curcumin-fed rats had less post-TBI oxidative damage than RD-fed rats Curcumin-fed rats with normalized post-TBI levels of hippocampal BDNF, synapsin I, and CREB than control-fed rats	Curcumin-fed rats performed better in post-TBI Morris water maze testing compared with RD fed rats
Laird et al. [101]	CD-1 mice Controlled cortical impact	Intraperitoneal curcumin 75, 150, or 300 mg kg−1 15 min prior to TBI, 30 min post-TBI, or 60 min post-TBI	Pretreatment with 75 or 150 mg kg−1 curcumin significantly reduced brain water content Pretreatment with 150 mg kg−1 curcumin significantly reduced expression of AQP4 Pretreatment with 150 mg kg−1 curcumin significantly reduced IL-1β expression Pretreatment with 150 mg kg−1 curcumin significantly reduced NF-κB expression	Pretreatment with 150 mg kg−1 curcumin significantly improved overall locomotion and movement within squares in the center of the open-field chamber after TBI Motor performance was unaffected by pretreatment with curcumin
Samini et al. [72]	Wistar rats Controlled cortical impact	Intraperitoneal curcumin 50 mg kg−1 day−1 100 mg kg−1 day−1 5 days before injury	Pretreatment with 100 mg kg−1 curcumin significantly reduced the size of brain lesions Pretreatment with 100 mg kg−1 curcumin significantly diminished post-TBI lipid peroxidation	Pretreatment with curcumin significantly improved sensory-motor performance
Sharma et al. [102]	Sprague–Dawley rats Mild fluid percussion injury	RD Curcumin diet Standard rat chow + 500 ppm curcumin	Curcumin-fed rats with normalized post-TBI levels of hippocampal pAMPK/AMPK ratio, uMtCK, UCP2, COX-II, and Sir2 compared with RD-fed rats

AMPK AMP-activated protein kinase, AQP4 aquaporin 4, BDNF brain-derived neurotrophic factor, COX-II cytochrome c oxidase II, Cr creatine, CrD regular diet enriched with 1% creatine monohydrate, CREB cyclic adenosine monophosphate response element-binding protein, HF high-fat diet, ICR Institute of Cancer Research, IL-1β interleukin-1β, NF-κB nuclear factor-kappa B, p-AMPK phosphorylated AMP-activated protein kinase, ppm parts-per million, RD regular diet, Sir2 silent information regulator 2, TBI traumatic brain injury, UCP2 mitochondrial uncoupling protein 2, uMtCK ubiquitous mitochondrial creatine kinase