Angiotensin receptor blocker, losartan ameliorates neuroinflammation and behavioral consequences of lipopolysaccharide injection

Losartan improved hippocampal long‐term potentiation impairment induced by repeated LPS injection in rats

“…In our previous studies, we have shown that pretreatment with losartan prevented brain inflammation and cognitive impairment in LPS‐treated mice (Salmani et al, 2020) and rats (Salmani et al, 2018). In the present study, we further investigated the protective effect of losartan on hippocampal LTP following repeated systemic inflammation.…”

“…Losartan was dissolved in pathogen‐free saline and stored at 4℃. The dose and duration of treatment with losartan were selected based on previous studies (Koh et al, 2013; Salmani et al, 2018). At 72 h after the last LPS injection, rats were anesthetized and used for the electrophysiological experiment.…”

Losartan Treatment Could Improve the Outcome of TBI Mice

“…The result that losartan treatment significantly improve the ratio of anti-inflammatory (IL-10) to pro-inflammatory (IL-6) cytokines in the brain after TBI may be one of the mechanisms of mouse recovery. Furthermore, losartan can directly act on microglia or astrocytes, and their protective benefits were verified in comparable studies (33,46,47). Previous studies have also confirmed that excessive AngII can activate rat neurons and microglia in vitro, and that losartan can block this effect (31,44).…”

“…Adult male C57BL/6 mice (8-10 weeks old, 22-25 g) were purchased from the Experimental Animal Laboratories of the Academy of Military Medical Sciences (Beijing, China). The dose of losartan (losartan potassium tablet, dissolved in 0.9% saline) was based on that previously reported (32,33). Mice were randomly assigned to receive losartan (3 mg/kg) or vehicle (0.09% sodium chloride solution) by oral gavage at 1 h after TBI, and then once per day.…”

Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation

“…Losartan reduced astrogliosis [ 118 ] Candesartan/Lisinopril ATR1/ACE Haloperidol-induced dyskinesia in rat model Co-administration of candesartan and lisinopril inhibited increase of TNFα and IL1β induced by haloperidol in the striatum and cortical regions of the rat brain [ 119 ] Candesartan ATR1 LPS-induced neuroinflammation in rat model Attenuation of microglial activation. Inhibition of pro-inflammatory cytokine production and NF-κB signaling [ 120 ] Losartan ATR1 Rat model of chronic hypertension (hypertension correlates with increased risks of PD) Intranasal administration of losartan increased brain IL-10 production, thus promoting neurogenesis by increasing choroid plexus cell proliferation [ 121 ] Candesartan ATR1 Alzheimer’s disease transgenic APP mouse model Candesartan administration decreased Iba-1 and GFAP expression in the brain [ 122 ] Candesartan/Telmisartan ATR1 Alpha-synuclein-induced Parkinson’s disease mouse model Co-administration of RAS inhibitory drugs decreased the expression of IL-6, IL1β, and iNOS in the substantia nigra and striatum of mice treated with adeno-associated virus encoding mutated alpha-synuclein) [ 123 ] Losartan ATR1 LPS-induced neuroinflammation in rat Pre-treatment with losartan before LPS administration decreased brain IL-6, malondialdehyde, and nitric oxide metabolites, improving behavioral parameters [ 124 ] Telmisartan ATR1 LPS-induced neuroinflammation in mouse Telmisartan decreased the TNFα and iNOS expression in brain together with a decrease in the brain Aβ plate deposition [ 125 ] Perindopril ACE LPS-induced neuroinflammation in mouse Perindopril improved spatial and non-spatial memory, decreased Aβ deposition, and reduced TNFα, iNOS, and malondialdehyde expression [ 126 ] Telmisartan ATR1 MPTP-induced Parkinson’s disease mouse model Telmisartan induces the activation of PPAR-γ in microglia, imprinting an anti-...…”