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Updated: Oct 17, 2025
A Simplified Operation for the Endovascular Perforation Murine Model of Subarachnoid Hemorrhage
Published on: June 13, 2025
Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage
Zhiyuan Vera Zheng1,2, Junfan Chen1, Hao Lyu1
1Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.
Background And Purpose:
Signal transducer and activator of transcription 3 (STAT3) may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses. Thus, this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage (SAH).
Methods:
The SAH model was established by endovascular perforation in the mouse. Real-time PCR (RtPCR) and western blot were used to examine the dynamic STAT3 signalling pathway responses after SAH. To clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH, the microglia-specific STAT3 knockout (KO) mice were generated by the Cre-LoxP system. The neurological functions were assessed by Catwalk and Morris water maze tests. Neuronal loss after SAH was determined by immunohistochemistry staining. Microglial polarisation status after STAT3 KO was then examined by RtPCR and immunofluorescence.
Results:
The STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after SAH. Downstream factors and related mediators altered dynamically and accordingly. Microglial STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after SAH. To investigate the underlying mechanism, we examined the microglial reaction after STAT3 KO. STAT3 deletion reversed the increase of microglia after SAH. Loss of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 polarisation. Functionally, microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early phase.
Conclusions:
STAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent neuroinflammation. Microglial STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inflammatory responses after SAH. STAT3 may serve as a promising therapeutic target to alleviate early brain injury after SAH.
Insights
Signal transducer and activator of transcription 3 (STAT3) plays a key role in neuroinflammation after subarachnoid hemorrhage (SAH). Inhibiting STAT3 in microglia improved neurological function and reduced brain injury by promoting anti-inflammatory responses.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is implicated in central nervous system inflammation.
- Microglial responses are critical in neuroinflammatory diseases like subarachnoid hemorrhage (SAH).
Purpose of the Study:
- To investigate the role of STAT3 in microglia-dependent neuroinflammation following experimental SAH.
- To assess the impact of STAT3 modulation on functional outcomes and neuronal survival post-SAH.
Main Methods:
- Established a mouse model of SAH via endovascular perforation.
- Utilized real-time PCR and western blot to analyze STAT3 signaling pathway dynamics.
- Generated microglia-specific STAT3 knockout (KO) mice using the Cre-LoxP system.
- Assessed neurological function using Catwalk and Morris water maze tests.
- Determined neuronal loss via immunohistochemistry and microglial polarization via RT-PCR and immunofluorescence.
Main Results:
- STAT3 and JAK2 signaling were rapidly activated post-SAH.
- Microglial STAT3 deletion significantly improved neurological impairment and reduced early neuronal loss.
- STAT3 deletion reversed SAH-induced microglial proliferation and promoted M1 to M2 polarization.
- Microglial STAT3 suppression reduced pro-inflammatory and enhanced anti-inflammatory responses in the early SAH phase.
Conclusions:
- STAT3 is integral to microglial polarization and neuroinflammation modulation after SAH.
- Deleting STAT3 in microglia enhances neurological function and neuronal survival, likely via M2 polarization and anti-inflammatory effects.
- Targeting microglial STAT3 presents a potential therapeutic strategy for mitigating early brain injury following SAH.
