Spinal cord astrocytes regulate myocardial ischemia–reperfusion injury

Wu, Chao; Liu, Rongrong; Luo, Zhaofei; Sun, Meiyan; Qile, Muge; Xu, Shijie; Jin, Shiyun; Zhang, Li; Gross, Eric R.; Zhang, Ye; He, Songqing

doi:10.1007/s00395-022-00968-x

Cited by 9 publications

(4 citation statements)

References 72 publications

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“…9, associated with a signi cant improvement of the neurological function compared to control group. Interestingly, the dose of FC that we used here is thought to speci cally trigger astrocytes TCA cycle [37]. In line with this, the FC injection in our model decreased the number of reactive astrocytes and the number of degenerative neurons in the brain after 48h following ROSC whether oxamate administration only reduced the number of degenerative neurons without any detectable effect on astrocytes reactivity.…”

Section: Discussionsupporting

confidence: 77%

Cerebral consumption of lactate contributes to neurological injury after experimental cardiac arrest in rabbits

Faucher,

Demelos,

Boissady

et al. 2024

Preprint

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Background: During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Methods: Rabbits were surgically instrumented and submitted to 10 min of ventricular fibrillation. After cardiopulmonary resuscitation, they were followed during 4 hours for the evaluation of the cerebral consumption and concentrations of several metabolites (n=6 / group) or during 48 hours for the evaluation of the neurological outcome (n=7 per group). In a first protocol, rabbits received either lactate, pyruvate or vehicle. In a second protocol, they received oxamate (LDH inhibitor), fluorocitrate (inhibitor of tricarboxylic acid cycle) or vehicle (Oxa, FC and Control groups). Finally, in a third protocol, they were submitted to rapid hypothermia induced by total liquid ventilation as an established neuroprotective approach, as compared to normothermia (TLV and Control groups). Results: In the first protocol, lactate and pyruvate administration enhanced metabolic disorders and cerebral consumption of lactate after cardiac arrest. This was associated with increased neurological dysfunction (median score = 72% [64 – 100], 100% [80 – 100] and 53% [38 – 60] in Lactate, Pyruvate and Control group respectively) at 48 hours after cardiac arrest. In the second protocol, oxamate and FC inhibited lactate metabolism vs Control and subsequently improved neurological recovery (median score = 15% [0 – 45], 16% [0 – 55] and 62% [38 – 72],for Oxa, FC and Control groups, respectively). In the third protocol, rapid hypothermia by TLV both mitigated lactate metabolism and and improved the neurological recovery. Conclusions: After cardiac arrest, cerebral oxidation of lactate into pyruvate by the neurons is deleterious. LDH inhibition might represent a promising therapeutic strategy for neuroprotection in this setting.

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Section: Discussionsupporting

confidence: 77%

Cerebral consumption of lactate contributes to neurological injury after experimental cardiac arrest in rabbits

Faucher,

Demelos,

Boissady

et al. 2024

Preprint

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“…Furthermore, since the participation of microglia in MIRI is well established, 47 , 48 we investigated whether preconditioning with EA brings changes in microglial morphology by quantitative 3D microglial morphometric measurements ( Figure 5 A). We observed that EA-pre inhibited excessive activation of FN Microglial in MIRI-induced FN ( Figure 5 B).…”

Section: Resultsmentioning

confidence: 99%

Electroacupuncture attenuates myocardial ischemia-reperfusion injury by inhibiting microglial engulfment of dendritic spines

Zhang,

Wang,

Zhou

et al. 2023

iScience

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“…Except for Ca 2+ activity, results were also inconsistent regarding the CNO‐induced cFOS expression. One study reported that the initial increment in Ca 2+ levels following Gi pathway activation is sufficient to induce cFOS expression in hippocampal astrocytes (Kol et al, 2020), while another reported that hM4Di activation reduces the number of cFOS‐positive astrocytes in the spinal cord within several hours after myocardial ischemia‐reperfusion injury (Wu et al, 2022). In our study, we found that at 3 or 14 days after stroke injury, little astrocytes in the peri‐infarcted cortex express cFOS, and hM4Di activation significantly increases the colocalization of GFAP and cFOS.…”

Section: Discussionmentioning

confidence: 99%

Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke

Wu,

Li,

et al. 2024

Glia

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Ischemic stroke is the leading cause of adult disability. The rewiring of surviving neurons is the fundamental process for functional recovery. Accumulating evidence implicates astrocytes in synapses and neural circuits formation, but few studies have further studied how to enhance the effects of astrocytes on synapse and circuits after stroke and its impacts on post‐stroke functional recovery. In this study, we made use of chemogenetics to specifically activate astrocytic Gi signaling in the peri‐infarcted sensorimotor cortex at different time epochs in a mouse model of photothrombotic stroke. We found that early activation of astrocytic hM4Di after stroke by CNO modulates astrocyte activity and upregulates synaptogenic molecules including thrombospondin‐1 (TSP1) as revealed by bulk RNA‐sequencing, but no significant improvement was observed in dendritic spine density and behavioral performance in grid walking test. Interestingly, when the manipulation was initiated at the subacute phase of stroke, the recovery of spine density and motor function could be effectively promoted, accompanied by increased TSP1 expression. Our data highlight the important role of astrocytes in synapse remodeling during the repair phase of stroke and suggest astrocytic Gi signaling activation as a potential strategy for synapse regeneration, circuit rewiring, and functional recovery.

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Spinal cord astrocytes regulate myocardial ischemia–reperfusion injury

Cited by 9 publications

References 72 publications

Cerebral consumption of lactate contributes to neurological injury after experimental cardiac arrest in rabbits

Cerebral consumption of lactate contributes to neurological injury after experimental cardiac arrest in rabbits

Electroacupuncture attenuates myocardial ischemia-reperfusion injury by inhibiting microglial engulfment of dendritic spines

Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke

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