. Author manuscript; available in PMC: 2022 Aug 1.

Published in final edited form as: Metab Brain Dis. 2021 Apr 9;36(6):1079–1086. doi: 10.1007/s11011-021-00728-1

Table 1.

Summary of experiments on RAS alteration in TBI

Study (Ref.)	Animal Model	Treatment	Dose and Duration	Result

Timaru-Kast, R (Timaru-Kast et al. 2019)	CCI - C57B16N Young, 2 months. Old, 21 months. male mice	Candesartan 10μg/ml	0.1 mg/kg/ SC/ 30 min after injury	Reduction in brain damage and neurological impairment through microglial response reduction and neutrophil granulocyte infiltration.

Janatpour, ZC (Janatpour et al. 2019)	CCI - C57BL/6NCr 8–10-week-old male mice	Ang (1–7) 10.0 mg/mL (micro-osmotic pump); 0.1mg/mL (injections)	1.0 mg/kg/day 2.5 mg/kg/day	Ang-(1–7) improved functional recovery and decreases glial activation.

Khaksari, M (Khaksari et al. 2018)	Wistar Male rats Diffuse TBI induced by Marmarou method	Candesartan	0.3 mg/kg IP, 30 min post-TBI	Reduction in brain edema, BBB disruption, oxidant activity, and ICP level using AT₁R inhibition.

Abdul-Muneer, PM (Abdul-Muneer et al. 2018)	E17 Sprague-Dawley rat embryos Stretch injury	Losartan	(100 μg/mL) 30 min prior to the stretch injury	Losartan downregulated oxidative markers, neuroinflammation and neurodegeneration

Villapol, S (Villapol et al. 2015)	CCI - C57BL/6NCr 9-week-old male mice	Candesartan	0.1, 0.5 or 1 mg/kg IP (after injury)	Neuroprotective. Candesartan is better than telmisartan in chronic condition and low dose of candesartan does not affect blood pressure.
	C57BL/6J WT control mice AT₁R knockout mice	Telmisartan	1 or 10 mg/kg once per day oral gavage
		PPARγ antagonist (T0070907)	2 mg/kg (after insult)

Umschweif, G (Umschweif et al. 2014b)	CHI - Sabra (Weight Drop Injury) 9–10-week-old male mice	AT₂ antagonist PD123319	10 mg/kg/day for 3 days (after injury)	HA stimulated AT₂R and increased neuroprotection and neurogenesis. AT₂R inhibition reduced these effects.

Timaru-Kast, R (Timaru-Kast et al. 2012)	CCI - C57B16N male mice	Candesartan	low (0.1 mg/kg) med. (0.5 mg/kg) high (1 mg/kg,) SC (30 min after insult)	AT₁R repression declined secondary brain damage and inflammation

Umschweif, G (Umschweif et al. 2014a)	CHI - Sabra 9–10-week-old mice	PD 123319	10 mg/kg/day	AT₂R activation improved neuroprotection and neurogenesis, through different pathways.
		CGP42112A	0.1, 1.0, or 10.0 ng/kg/min, 3 days post-CHI

Villapol, S (Villapol et al. 2012)	CCI - C57BL/6 9-week-old male mice	Candesartan	1 mg/kg/day	Reduction in neuronal cell death and microglial activation
		PPARγ antagonist T0070907	1.5 mg/kg