Delayed creatine supplementation counteracts reduction of GABAergic function and protects against seizures susceptibility after traumatic brain injury in rats

Nutritional interventions to improve neurophysiological impairments following traumatic brain injury: A systematic review

“…Application of inclusion and exclusion criteria to titles and abstracts of search resulted in 201 full‐text articles that were screened for eligibility; 43 journal articles (Bailes & Mills, 2010; Cheng et al., 2016; Cole et al., 2010; Davis et al., 2008; Deng‐Bryant et al., 2011; Elliott et al., 2018; Gerbatin et al., 2019; Greco et al., 2016; Hu, Wang, Jin, et al., 2009; Hu, Wang, Qiao, et al., 2009; Itoh et al., 2013; Ji et al., 2017; Jiang et al., 2017; Krishna et al., 2019; Kumar et al., 2014; Lim et al., 2013; Liu et al., 2017; Mills et al., 2011; Ozbal et al., 2015; Özevren et al., 2018; Prins et al., 2005; Prins & Hovda, 2009; Rubovitch et al., 2019; Saraiva et al., 2012; Schober et al., 2016; Schwartzkroin et al., 2010; Sharma et al., 2010; Shin & Dixon, 2011; Su et al., 2016; Thau‐Zuchman et al., 2019; Toklu et al., 2009; Wang et al., 2018; Wang, Li, et al., 2016; Wang, Zhang, et al, 2016; Wei et al., 2015; Wu et al., 2011, 2014; Xie et al., 2018; Xing et al., 2016; Xu et al., 2017; Zhang et al, 2018; Zhao et al., 2014; Zhu et al., 2017) met all eligibility criteria. Most studies (28/43) were conducted since 2013, with four to seven new studies being released each year since 2016.…”

“…Two studies interrogated the effect of creatine supplementation, delivered by oral gavage, on NP outcomes post‐TBI (Gerbatin et al., 2019; Saraiva et al., 2012). Creatine reduced oxidative stress and cellular energy imbalance (Saraiva et al., 2012) and there was reduced cells lost within the hippocampus and increased inhibitory neuron action versus control (Gerbatin et al., 2019). Increased inhibitory action associated with creatine supplementation also had a protective effect against drug‐induced seizures (to simulate epileptic seizures post‐TBI) versus control in one study (Gerbatin et al., 2019).…”

“… natural compounds with known anti‐oxidant properties (Cheng et al., 2016; Itoh et al., 2013; Ji et al., 2017; Jiang et al., 2017; Krishna et al., 2019; Ozbal et al., 2015; Toklu et al., 2009; Wei et al., 2015); branched chain amino acids (BCAA) (Cole et al., 2010; Elliott et al., 2018; Lim et al., 2013); creatine (Gerbatin et al., 2019; Saraiva et al., 2012); fasting and caloric restriction (Davis et al., 2008; Liu et al., 2017; Rubovitch et al., 2019); KD (Deng‐Bryant et al., 2011; Greco et al., 2016; Hu, Wang, Jin, et al., 2009; Hu, Wang, Qiao, et al., 2009; Prins et al., 2005; Prins & Hovda, 2009; Schwartzkroin et al., 2010; Zhang et al., 2018); multi‐supplements (Thau‐Zuchman et al., 2019; Wu et al., 2014); ω‐3 polyunsaturated fatty acids (PUFAs) (Bailes & Mills, 2010; Mills et al., 2011; Schober et al., 2016; Shin & Dixon, 2011; Su et al., 2016; Wu et al., 2011; Zhu et al., 2017); or natural compounds used in traditional eastern medicine (Kumar et al., 2014; Özevren et al., 2018; Sharma et al., 2010; Wang et al., 2018; Wang, Fan, et al, 2016; Wang, Zhang, et al, 2016; Xie et al., 2018; Xing et al., 2016; Zhao et al., 2014). …”

“…To overcome this issue animals belonging to the same study groups may have been housed together. To enhance methodological transparency, it is recommended that future studies incorporate a figure/diagram that clearly depicts key aspects of study design as shown in some studies (Gerbatin et al, 2019;Itoh et al, 2013;Kumar et al, 2014;Saraiva et al, 2012;Schwartzkroin et al, 2010;Thau-Zuchman et al, 2019;Xing et al, 2016). are the focus of ongoing initiatives (Collins & Tabak, 2014;Hiskens et al, 2019;Hooijmans et al, 2012Hooijmans et al, , 2014Kilkenny et al, 2010;Landis et al, 2012;Mohamadpour et al, 2019;Wojnarowicz et al, 2017).…”

Maternal Creatine Supplementation Positively Affects Male Rat Hippocampal Synaptic Plasticity in Adult Offspring

“…On the other hand, enhanced neuron excitability could translate into higher network excitability resulting in an increased susceptibility to the generation of seizure episodes; however, our unpublished data do not show any spontaneous or induced epileptiform-like activity in hippocampal slices obtained from maternally creatine treated rat pups. Moreover, creatine supplementation is known to play a neuroprotective role in brain excitability by controlling the γ-aminobutyric acid (GABA)ergic function [18]. Therefore, in the present study, to verify possible long-term effects of prenatal creatine treatments we analyzed the morpho-functional features of hippocampal CA1 neurons in adult rats born from dams supplemented with creatine using morphological, electrophysiological and calcium imaging approaches.…”