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Review
. 2025 Aug 7;20(1):20251248.
doi: 10.1515/med-2025-1248. eCollection 2025.

PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy

Yang Guo  1 , Yonghao Yu  1
Affiliations
Review

PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy

Yang Guo et al. Open Med (Wars). .

Abstract

Background: Sepsis-associated encephalopathy (SAE) is a complex neurological complication of sepsis involving activation of microglia in the central nervous system (CNS), blood-brain barrier (BBB) dysfunction, neurotransmitter dysfunction, impaired brain metabolism, and mitochondrial dysfunction. Neuroinflammation is a critical component of the pathogenesis. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as a key intracellular signaling pathway, plays a crucial role in regulating neuroinflammation, maintaining the integrity of the BBB, and promoting neuronal cell survival.

Objective: This review aims to summarize the role of the PI3K/Akt pathway in SAE-associated neuroinflammation and highlights potential therapeutic targets and strategies for its management.

Methods: We systematically reviewed recent basic and clinical studies on PI3K/Akt signaling pathway in neuroinflammation associated with SAE, as well as the development of pathway-specific agonists and inhibitors.

Results: The PI3K/Akt pathway serves as a crucial intracellular signaling axis involved in the regulation of neuroinflammatory processes. Accumulating evidence indicates that targeted modulation of this pathway may alleviate neuroinflammation associated with SAE and enhance neurological recovery.

Conclusion: Targeting the PI3K/Akt pathway represents a promising therapeutic approach for SAE. Advances in the development of specific agonists and inhibitors provide new opportunities for clinical translation and drug discovery in neuroinflammatory conditions.

Keywords: PI3K/Akt pathway; blood–brain barrier; cognitive dysfunction; neuroinflammation; sepsis-associated encephalopathy.

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Conflict of interest statement

Conflict of interest: Authors state no conflict of interest.

Figures

Figure 1
Figure 1
Differences in PI3K/Akt pathway in normal brain tissue and SAE conditions. ROS: reactive oxygen species.
Figure 2
Figure 2
Inflammatory signaling regulates SAE through the PI3K/Akt pathway. PAMPs: pathogen-associated molecular patterns; DAMPS: damage-associated molecular patterns; LTA: lipoteichoic acid; NTS: nucleus tractus solitarius; BBB: blood–brain barrier.
See this image and copyright information in PMC

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