Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction

Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress

“…Poor cognitive performance has also been reported in chronically fatigued patients (Joyce et al 1996). Centrally administered renin and Ang-II are known to disrupt cognition possible mediated through AT1 receptors and documented to be associated with cholinergic system (Li et al 2014;Wayner et al 1993). Besides, Ang-II is also known to affect the production of COX-2 and other inflammatory pathways via NF-kB expression which plays crucial role in cognitive dysfunction (Zhang et al 2014).…”

“…Ang-II, via AT-1 receptor activation can increase leukocyte transmigration across vessel walls and tissues (Alvarez et al 2001), enhances the expression of chemokines, adhesion molecules (Mervaala et al 1999;Suzuki et al 2003;Tsutamoto et al 2000;Zhao et al 2004) and cytokines (mediated by NF-jB and AP-1) (Chan and Leung 2007;Liu et al 2006;Suzuki et al 2003) by acting on endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Further, it is well known that COX-2 and TNF-a expression lies down stream to NF-kB which is regulated by Ang-II Li et al 2014), it is reasonable to conjecture that simultaneously targeting Ang-II and COX-2 could be advantageous. Owing to this in the present study also treatment with losartan and nimesulide has been shown to reduce the TNF-a and CRP levels suggesting their antiinflammatory action.…”

Postoperative Cognitive Dysfunction: Preclinical Highlights and Perspectives on Preventive Strategies

“…In fact, surgery induces peripheral immune challenges, leading to an exaggerated neuroinlammatory response. More recently, several studies have demo nstrated that neuroinlammation in the hippocampus is most likely to be involved in the pathogenesis of POCD [35,[44][45][46][47][48][49][50][51]. Neuroinlammation is a complex response to brain injury characterized by maladaptive microglial activation mainly involving the activation of glia and increased levels of pro-inlammatory cytokines, including interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) [52][53][54].…”

“…When the efects of postoperative analgesia with ketoprofen on cognitive functions were investigated in aged animals, the results suggested that ketoprofen can prevent the development of surgery-associated memory deficits via its pain-relieving effects [79]. Chronic pretreatment with low doses of candesartan may elicit blood pressure-independent neuroprotective effects in POCD by decreasing hippocampal bloodbrain barrier permeability and promoting resolution of neuroinflammation [47]. Further, dexmedetomidine provided neurocognitive protection, attenuating isoflurane-induced injury in rats developing brain [80].…”

Surgical procedures and postoperative cognitive dysfunction

“…POCD animal models show postoperative hippocampal neuroinflammation marked by bloodbrain barrier (BBB) disruption, glial response, and activation of inflammation / NF-κB signalling. Li et al 18 investigated modulation of the brain renin-angiotensin system in an aged rat model of POCD and the influence of angiotensin-1 inhibition (AT1 inhibition) on neurobehavioral outcome, BBB permeability, and brain inflammation after surgery. They observed significant inhibition of hippocampal neuroinflammation, evidenced by decreased glial reactivity and phosphorylation of the NF-κB p65 subunit, as well as marked reductions in interleukin-1β, tumour necrosis factor-alpha, and cyclooxygenase-2.…”