Natural antioxidant formula ameliorates lipopolysaccharide-induced impairment of hippocampal neurogenesis and contextual fear memory through suppression of neuroinflammation in rats

Zeng, Wen; Takashima, Kazumi; Tang, Qian; Zou, Xinyu; Ojiro, Ryota; Ozawa, Shunsuke; Jin, Minghua; Ando, Yujiro; Yoshida, Toshinori; Shibutani, Makoto

doi:10.1016/j.jchemneu.2023.102285

Cited by 1 publication

(1 citation statement)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neuroin ammation is considered a potential mechanism of the aberrant proliferation and differentiation of hippocampal NSCs [17]. Improvement of hippocampal neurogenesis de cits by anti-oxidant and anti-in ammatory activities can ameliorate post-sepsis cognitive dysfunction in adult animals [18,19]. Dexmedetomidine, a highly selective α2-adrenoceptor agonist, is widely used as an effective auxiliary medicine in clinical anesthesia and ICU owing to its sedative, analgesic and anti-sympathetic effects [20].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine attenuates neuroinflammation-mediated hippocampal neurogenesis impairment in sepsis-associated encephalopathy mice through central α2A-adrenoceptor

Guo,

Zhang,

Dai

et al. 2023

Preprint

View full text Add to dashboard Cite

Sepsis-associated encephalopathy (SAE), one of the common complications of sepsis, is associated with higher ICU mortality, prolonged hospitalization and long-term cognitive decline. Sepsis can induce neuroinflammation, which negatively affects hippocampal neurogenesis. Dexmedetomidine has been shown to protect against SAE. However, the potential mechanism remains unclear. In this study, we added lipopolysaccharide (LPS)-stimulated astrocytes-conditioned media (LPS-CM) to neural stem cells (NSCs) culture, which were pretreated with dexmedetomidine in the presence or absence of the α2-adrenoceptor antagonist yohimbine or the α2A-adrenoceptor antagonist BRL-44408. LPS-CM impaired the neurogenesis of NSCs, characterized by decreased proliferation, enhanced gliogenesis and declined viability. Dexmedetomidine alleviated LPS-CM-induced impairments of neurogenesis in a dose-dependent manner. Yohimbine, as well as BRL-44408, reversed the effects of dexmedetomidine. We established a mouse model of SAE by cecal ligation and perforation (CLP). CLP induced astrocyte-related neuroinflammation and hippocampal neurogenesis deficits, companied with learning and memory decline, which was reversed by dexmedetomidine. The effect of dexmedetomidine was blocked by BRL-44408. Collectively, our findings support the conclusion that dexmedetomidine can protect against SAE, likely mediated by the combination of inhibiting neuroinflammation via astrocytic α2A-adrenoceptor with attenuating neuroinflammation-induced hippocampal neurogenesis deficits via NSCs α2A-adrenoceptor.

show abstract

Section: Introductionmentioning

confidence: 99%