PUBLICATION

General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish

Authors

Xu, D.J., Wang, B., Zhao, X., Zheng, Y., Du, J.L., Wang, Y.W.

ID

ZDB-PUB-170906-8

Date

2017

Source

Molecular brain 10: 44 (Journal)

Registered Authors

Du, Jiu Lin

Keywords

Brain injury, Ca2+ wave, Cardiac arrest, General anesthetics, Zebrafish

MeSH Terms

Anesthetics, General/pharmacology
Anesthetics, General/therapeutic use*
Neuroprotective Agents/therapeutic use*
Brain/drug effects
Brain/metabolism
Brain/pathology
Brain/physiopathology
Calcium Signaling*/drug effects
Animals
Motor Activity/drug effects
Zebrafish/metabolism*
Apoptosis/drug effects
Heart Arrest/complications*
Heart Arrest/physiopathology
Brain Injuries/drug therapy*
Brain Injuries/etiology*
Brain Injuries/physiopathology
Midazolam/pharmacology
Midazolam/therapeutic use
Ketamine/pharmacology
Ketamine/therapeutic use
Survival Analysis

(all 22)

PubMed

28870222 Full text @ Mol. Brain

Abstract

Cardiac arrest is a leading cause of death and disability worldwide. Although many victims are initially resuscitated, they often suffer from serious brain injury, even leading to a "persistent vegetative state". Therefore, it is need to explore therapies which restore and protect brain function after cardiac arrest. In the present study, using Tg (HuC:GCaMP5) zebrafish as a model, we found the zebrafish brain generated a burst of Ca²⁺ wave after cardiac arrest by in vivo time-lapse confocal imaging. The Ca²⁺ wave was firstly initiated at hindbrain and then sequentially propagated to midbrain and telencephalon, the neuron displayed Ca²⁺ overload after Ca²⁺ wave propagation. Consistent with this, our study further demonstrated neuronal apoptosis was increased in cardiac arrest zebrafish by TUNEL staining. The cardiac arrest-induced Ca²⁺ wave propagation can be prevented by general anesthetics such as midazolam or ketamine pretreatment. Moreover, midazolam or ketamine pretreatment dramatically decreased the neuronal apoptosis and improved the survival rate in CA zebrafish. Taken together, these findings provide the first in vivo evidence that general anesthetics pretreatment protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
zf585Tg	mechanical stress	Days 7-13	brain apoptotic, abnormal	Fig. 3
zf585Tg	mechanical stress	Days 7-13	brain calcium-mediated signaling increased occurrence, abnormal	Fig. 1
zf585Tg	mechanical stress	Days 7-13	brain calcium-mediated signaling increased occurrence, abnormal	Fig. 2
zf585Tg	mechanical stress	Days 7-13	swimming decreased duration, abnormal	Fig. 4
zf585Tg	mechanical stress	Days 7-13	swimming decreased occurrence, abnormal	Fig. 4
zf585Tg	mechanical stress	Days 7-13	whole organism viability, abnormal	Fig. 4
zf585Tg	mechanical stress, chemical treatment by environment: ketamine	Days 7-13	brain apoptotic, ameliorated	Fig. 3
zf585Tg	mechanical stress, chemical treatment by environment: ketamine	Days 7-13	brain calcium-mediated signaling increased occurrence, ameliorated	Fig. 2
zf585Tg	mechanical stress, chemical treatment by environment: ketamine	Days 7-13	swimming decreased duration, abnormal	Fig. 4
zf585Tg	mechanical stress, chemical treatment by environment: ketamine	Days 7-13	swimming decreased occurrence, abnormal	Fig. 4

1 - 10 of 16

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
zf585Tg	Tg2(elavl3:GCaMP5G)	Transgenic Insertion

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
cardiac arrest	WT	mechanical stress	TAS
post-cardiac arrest syndrome			TAS

Sequence Targeting Reagents

Fish

Fish
WT
zf585Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GCaMP	EFG	GCaMP

Mapping

Xu et al., 2017 ZDB-PUB-170906-8 PMID:28870222

General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish

Xu et al., 2017

ZDB-PUB-170906-8
PMID:28870222