Annexin A7 induction of neuronal apoptosis via effect on glutamate release in a rat model of subarachnoid hemorrhage

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OBJECTIVE

Glutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.

METHODS

Endovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction.

RESULTS

ANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression.

CONCLUSIONS

ANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.

ABBREVIATIONS ANXA7 = annexin A7; BBB = blood-brain barrier; ELISA = enzyme-linked immunosorbent assay; GFAP = glial fibrillary acidic protein; ICH = intracerebral hemorrhage; NSE = neuron-specific enolase; PBS = phosphate-buffered saline; SAH = subarachnoid hemorrhage; SNAP = synaptosome-associated protein; TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.
Article Information

Contributor Notes

Correspondence De-Zhi Kang: First Affiliated Hospital of Fujian Medical University, Fujian, China. kdzz99988@163.com.INCLUDE WHEN CITING Published online February 1, 2019; DOI: 10.3171/2018.9.JNS182003.

Q.S.L. and W.X.W. contributed equally to this article.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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