Losartan modulates brain inflammation and improves mood disorders and memory impairment induced by innate immune activation: The role of PPAR-γ activation

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

“…Previous studies have shown that AT1R blockade by ARBs improves cognitive impairment in various models of brain inflammation (Khallaf et al, 2017; Quiñones et al, 2016; Villapol et al, 2015; Wincewicz & Braszko, 2015). Neuroprotective effects of losartan, as a selective AT1R blocker, in various models of brain disease have also been reported in previous studies (Salmani et al, 2020; Singh et al, 2017; Sun et al, 2015). In addition, in a mouse model of Alzheimer's disease, treatment with losartan has been reported to improve cerebrovascular function (Papadopoulos et al, 2017).…”

“…Previous studies have shown that AT1R blockade following systemic inflammation ameliorates brain inflammation (Benicky et al, 2011; Saavedra, 2012). Our previous study also showed that losartan prevented brain inflammation by reducing the inflammatory cytokines IL‐1β and TNF‐α in hippocampal tissues (Salmani et al, 2020). Both of these cytokines are highly expressed in a diseased brain, and both of them have been reported to directly suppress hippocampal LTP (Prieto et al, 2019).…”

“…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.…”

“…Our previous studies showed that IL-1β and TNF-α levels in the brain tissue of repeated LPS-injected mice were significantly higher than the control animals even 2 weeks after LPS withdrawal (Salmani et al, 2020(Salmani et al, , 2021. In physiological concentrations, IL-1β enhances hippocampal LTP and memory function, whereas, in pathological concentrations, it suppresses LTP and induces memory impairment (Goshen et al, 2007;Ross et al, 2003).…”

“…Additionally, it has been indicated that brain levels of Ang II and AT1R expression were increased in the LPS‐injected animals, as well as in glial cell culture exposed to LPS (Benicky et al, 2011; Bhat et al, 2016). Previous studies have shown that AT1R blockers (ARBs) prevent brain inflammation following systemic inflammation (Benicky et al, 2011; Salmani et al, 2020). Furthermore, Ang II directly modulates brain function, including processes related to learning and memory.…”