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Enhancement of Ca2+ Signal Strength in Astrocytes in the Lateral Septum Improves Cognitive Disorders in Mice After Hemorrhagic Shock and Resuscitation

 Wen‑Guang Li1,2  · Lan‑Xin Li1  · Rong‑Xin Song3  · Xu‑Peng Wang4  · Shi‑Yan Jia1  · Xiao‑Yi Ma1,5 · Jing‑Yu Zhang6  · Gang‑Feng Yin7  · Xiao‑Ming Li8  · Li‑Min Zhang1,3
1 Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation, Cangzhou 061000, China 
2 Graduate School, Hebei Medical University, Shijiazhuang 050011, China 
3 Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital), Cangzhou 061000, China 
4 The Third Hospital of Hebei Medical University, Shijiazhuang 050011, China 
5 Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital), Hebei University of Chinese Medicine, Cangzhou 061000, China 
6 Clinical Lab, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital), Cangzhou 050200, China 
7 Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou 061000, China 
8 Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research, Cangzhou 061000, China

Abstract
Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca2+ signal strength in lateral septum astrocytes following HSR.

Keywords
HSR · Astrocytes · Ca2+ signal · Cognition · Cross-frequency coupling