Promoting endothelial function by S-nitrosoglutathione through the HIF-1α/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats

Drug Design, Development and Therapy, 2015 · DOI: http://dx.doi.org/10.2147/DDDT.S77115 · Published: April 17, 2015

Simple Explanation

This study investigates how S-nitrosoglutathione (GSNO) can help the brain repair itself and improve function after a stroke in rats. GSNO is a natural substance in the body that can protect and repair nerve cells. The researchers found that GSNO stimulates the production of substances like HIF-1α and VEGF, which are important for forming new blood vessels and repairing brain tissue after a stroke. By promoting the formation of new blood vessels and nerve repair, GSNO can improve motor skills and overall neurological function after a stroke, showing promise as a potential treatment.

Study Duration

7 or 14 days

Participants

121 male Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
GSNO treatment enhanced the expression of HIF-1α, VEGF, and PECAM-1, which are neurorepair mediators, in rats after a stroke.
2
GSNO treatment increased vessel density in the brain, indicating that it promotes angiogenesis, which is the formation of new blood vessels.
3
Inhibiting HIF-1α blocked the beneficial effects of GSNO, suggesting that GSNO's neuroprotective effects are dependent on the HIF-1α pathway.

Research Summary

This study demonstrates that GSNO stimulates neurorepair processes, promotes angiogenesis, and aids functional recovery in rats after experimental stroke. GSNO's beneficial effects are mediated through the HIF-1α-dependent pathway, showing therapeutic promise for stroke treatment. The study highlights the potential of GSNO as a novel therapeutic target for both acute and chronic phases of stroke by stabilizing HIF-1α and promoting neurovascular repair.

Practical Implications

Therapeutic Potential for Stroke

GSNO shows promise as a therapeutic agent for stroke, potentially improving outcomes in both acute and chronic phases of the condition.

Novel Target Mechanism

The study identifies HIF-1α stabilization as a novel target mechanism for stroke therapy, opening new avenues for drug development.

Translational Relevance

GSNO's natural occurrence in the human body and lack of known side effects make it a highly translatable therapeutic option.

Study Limitations

1
Did not identify Ki67-positive cell types.
2
The role of the GSNO/HIF-1α/VEGF pathway in permanent ischemic stroke is less clear.
3
A reduced level of both HIF-1α and VEGF in A + B + GSNO compared with A + B set was unanticipated and may be attributed to the stability of GSNO under bEnd3 cell transfection conditions.

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