The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

Cell Prolif., 2022 · DOI: 10.1111/cpr.13275 · Published: September 1, 2022

Simple Explanation

Traumatic spinal cord injury (TSCI) leads to loss of function below the injury site. The PI3K/AKT pathway is a potential therapeutic target. This review summarizes the role of this pathway in TSCI. Inflammation and cell death in the subacute phase worsen nerve cell survival. Mature glial scar formation in the chronic phase inhibits axon regeneration. The PI3K/AKT pathway is important for spinal cord function recovery after injury. Activating it in the subacute phase and inhibiting it in the chronic phase may help treat TSCI.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Early apoptosis and autophagy after TSCI protect against injury; prolonged inflammation leads to accumulation of pro-inflammatory factors and excessive apoptosis, aggravating TSCI.
2
Initial glial scar formation is a protective mechanism that limits damage and inflammation; however, mature scar tissue hinders axon regeneration and prevents nerve function recovery.
3
Activation of the PI3K/AKT pathway can inhibit inflammation and apoptosis in the subacute phase; inhibiting this pathway in the chronic phase can reduce glial scar formation.

Research Summary

This review summarizes the pathological processes and mechanisms underlying inflammation, cell death and glial scar formation in secondary injury. In the acute phase of SCI, surgical intervention and suppression of inflammatory responses may be needed. In the subacute phase, apoptosis, disruption of autophagic flow and excessive autophagy should be suppressed. PI3K/AKT signalling pathway activation is involved in the subacute phase of secondary injury; inhibition of this pathway in the chronic phase may offer a strategy for the treatment of SCI.

Practical Implications

Therapeutic Target Identification

The PI3K/AKT pathway offers a potential therapeutic target for the inhibition of secondary SCI.

Subacute Phase Intervention

Inducing the activation of PI3K/AKT signaling pathway in the subacute phase of secondary injury may be a potential strategy.

Chronic Phase Intervention

Inhibiting PI3K/AKT pathway in the chronic phase may be one of the potential strategies for the treatment of TSCI.

Study Limitations

1
Classification of secondary injury phases may be inaccurate and requires further studies.
2
Regulation of NF-κB by the PI3K/AKT signalling pathway is controversial.
3
Further research is needed to determine whether activation or inhibition of the PI3K/AKT signalling pathway has anti-apoptotic effects.

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