Acute and long-term cognitive impairment following sepsis: mechanism and prevention

ABSTRACT

Introduction

Sepsis is a severe host response to infection, which induces both acute and long-term cognitive impairment. Despite its high incidence following sepsis, the underlying mechanisms remain elusive and effective treatments are not available clinically.

Area covered

This review focuses on elucidating the pathological mechanisms underlying cognitive impairment following sepsis. Specifically, the authors discuss the role of systemic inflammation response, blood–brain barrier disruption, neuroinflammation, mitochondrial dysfunction, neuronal dysfunction, and Aβ accumulation and tau phosphorylation in cognitive impairment after sepsis. Additionally, they review current strategies to ameliorate cognitive impairment.

Expert opinion

Potential interventions to reduce cognitive impairment after sepsis include earlier diagnosis and effective infection control, hemodynamic homeostasis, and adequate brain perfusion. Furthermore, interventions to reduce inflammatory response, reactive oxygen species, blood–brain barrier disruption, mitochondrial dysfunction, neuronal injury or death could be beneficial. Implementing strategies to minimize delirium, sleep disturbance, stress factors, and immobility are also recommended. Furthermore, avoiding neurotoxins and implementing early rehabilitation may also be important for preventing cognitive impairment after sepsis.

KEYWORDS:

• Sepsis
• cognitive impairment
• pathological mechanisms
• outcomes
• interventions

Article highlights

• Sepsis induces both acute and long-term cognitive impairments.

• The mechanisms underlying sepsis-induced cognitive impairment are not fully understood.

• Effective therapeutics for sepsis-induced cognitive impairment are not available clinically.

• Interventions to reduce cognitive impairment associated with sepsis might include earlier diagnosis and effective infection control, stabilizing hemodynamics and adequate brain perfusion.

• Interventions to attenuate inflammation, reactive oxygen species, blood–brain barrier disruption, mitochondrial dysfunction, and neuronal injury could be beneficial.

• Avoiding neurotoxins and early rehabilitation are also crucial.

Abbreviations

BBB	=	Blood-brain barrier;
BDNF	=	brain-derived neurotrophic factor;
CLP	=	Cecum ligation and puncture;
CNS	=	Central nervous system;
EEG	=	Electroencephalogram;
HMGB1	=	High mobility group protein 1;
HMG-CoA	=	Hydroxymethylglutaryl coenzyme A;
HO-1	=	Heme oxygenase-1;
ICU	=	Intensive care unit;
IFNs	=	Interferons;
IL	=	Interleukin;
LPS	=	Lipopolysaccharide;
MMPs	=	Matrix metalloproteinases;
NOX2	=	NADPH oxidase isoform 2;
NF-κB	=	Nuclear factor kappa B;
NLRP3	=	Nucleotide-binding domain-like receptor protein3;
NRG1	=	Neuregulin-1;
Nrf2	=	Nuclear factor erythroid-2 related factor;
proBDNF	=	precursor form of brain-derived neurotrophic factor;
PV	=	parvalbumin;
ROS	=	Reactive oxygen species;
SAE	=	Sepsis-associated encephalopathy;
TLRs	=	Toll-like receptors.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the grants from the National Natural Science Foundation of China (81971892 & 82172131).