Krüppel-like factor 7 attenuates hippocampal neuronal injury after traumatic brain injury

Neural Regeneration Research, 2022 · DOI: 10.4103/1673-5374.320991 · Published: March 1, 2022

Simple Explanation

This study investigates the role of Krüppel-like factor 7 (KLF7) in traumatic brain injury (TBI), focusing on its impact on hippocampal neurons. They created an in vitro model of TBI using HT22 cells subjected to stretch injury and oxygen-glucose deprivation and an in vivo model using mice with controlled cortical impact (CCI). The researchers found that overexpressing KLF7 reduced apoptosis (cell death) and increased the expression of proteins associated with neuronal survival. KLF7 overexpression also upregulated Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, suggesting involvement of the JAK2/STAT3 signaling pathway. In conclusion, KLF7 may protect hippocampal neurons after traumatic brain injury through activation of the JAK2/STAT3 signaling pathway, suggesting potential therapeutic benefits.

Study Duration

Not specified

Participants

72 C57BL/6 mice (36 males and 36 females)

Evidence Level

Level II; In vitro and in vivo study

Key Findings

1
KLF7 overexpression significantly reduced apoptosis, activated caspase-3 and lactate dehydrogenase, downregulated the expression of Bax and cleaved caspase-3, and increased the expression of βIII-tubulin and Bcl-2 in HT22 cells after stretch injury and oxygen-glucose deprivation.
2
KLF7 overexpression upregulated JAK2 and STAT3 phosphorylation in HT22 cells treated by stretch injury and oxygen-glucose deprivation, and KLF7 directly participated in the phosphorylation of STAT3.
3
In a mouse model of TBI, KLF7 reduced ipsilateral hippocampal atrophy, decreased the injured cortex volume, downregulated Bax and cleaved caspase-3 expression, and increased the number of 5-bromo-2′-deoxyuridine-positive neurons and Bcl-2 protein expression.

Research Summary

This study aimed to determine the function of KLF7 in stretch- and OGD-induced apoptosis of HT22 cells in vitro, and in TBI-induced hippocampal neuron damage in mice in vivo. The results suggest that KLF7 may protect hippocampal neurons after traumatic brain injury through activation of the JAK2/STAT3 signaling pathway. The neuroprotective role of KLF7 extends to in vitro and in vivo models of mild TBI, mitigating pro-apoptotic signals and preserving cell viability and proliferation, likely underlying the preservation of cortical volume and functional improvements.

Practical Implications

Therapeutic Potential

KLF7 could be a therapeutic target for mitigating neuronal damage after TBI.

Signaling Pathway

The JAK2/STAT3 signaling pathway is a key mediator in KLF7's neuroprotective effects, providing a specific target for intervention.

Axonal Regeneration

KLF7's role in axonal regeneration and outgrowth, well-characterized in SCI, suggests a potential mechanism for functional recovery after TBI.

Study Limitations

1
The in vitro TBI injury model omitted the cellular microenvironment.
2
Further study is needed to determine the precise molecular mechanisms underlying JAK2/STAT3 signaling activated by KLF7 in vivo.
3
Further work is needed to verify the protective ability of KLF7 overexpression across the spectrum of TBI severities.

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