Dose-Dependent Microglial and Astrocytic Responses Associated With Post-ischemic Neuroprotection After Lipopolysaccharide-Induced Sepsis-Like State in Mice

Abstract

In contrast to lipopolysaccharide (LPS)-induced preconditioning, which has repeatedly been examined in the past, the effects of post-ischemic LPS-induced sepsis, although clinically considerably more important, have not systemically been studied. We exposed mice to transient intraluminal middle cerebral artery occlusion (MCAO) and examined the effects of intraperitoneal LPS (0.1 or 1 mg/kg) which was administered 24 h postischemia. Post-ischemic glial reactivity, neuronal survival and neurological outcome were differently modulated by the higher and the lower LPS dose. Although both doses promoted neuronal survival after 72 h, the underlying mechanisms were not similar. Mice receiving 1 mg/kg LPS exhibited transient hypothermia at 1 and 3 hours post sepsis (hps), followed by reduced focal neurological deficits at 24, 48 and 72 hps. The lower dose (0.1 mg/kg) did not induce hypothermia, but reduced microglia/macrophage activation with the appearance of an anti-inflammatory CD206 positive cell phenotype in the brain parenchyma. Together, our results indicate a novel, dose-dependent modulation of microglial cells that is intricately involved in brain protection.

The impact of early life stress and immune challenge on behavior and glia cells alteration in late adolescent rats

“…In line with the revealed cross talk between astrocytes and microglia during neuroinflammation (Réus et al., 2019; Rothhammer et al., 2018; Sardari et al., 2020), we reported that LPS injection, as well LPS in maternally deprived rats, increased GFAP‐positive astrocyte. GFAP is a protein expressed by astrocytes and plays a role in cell movement and structure.…”

The renin-angiotensin system modulates endotoxic postconditioning of exacerbated renal vasoconstriction in preeclamptic offspring

“…Indeed, the phenomenon of pre- or post-insult conditioning has been designated for LPS and other interventions against biological offences. For example, post-ischemic treatment with LPS was shown to reduce infarct volume following middle cerebral artery occlusion 55 . Similarly, post-insult hypothermia resulted in amelioration of hippocampal neurodegeneration in the rodent model of preterm oxygen deprivation 56 .…”

Inflammatory responses involved in post-cardiac arrest brain injury: mechanisms, regulation, and therapeutic potential

“…Microglia, the resident innate immune cells in the brain, are activated rapidly after CA. Activated microglia polarize between a classically activated (M1, pro-inflammatory) phenotype or an alternatively activated (M2, anti-inflammatory) phenotype [16][17][18]. Microglia change dynamically and temporally into different phenotypes in different phases of injury, contributing to either tissue damage or repair in various brain diseases [19][20][21].…”