In:
Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 132, No. 3 ( 2020-03), p. 777-787
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0022-3085
,
1933-0693
DOI:
10.3171/2018.9.JNS182003
Sprache:
Unbekannt
Verlag:
Journal of Neurosurgery Publishing Group (JNSPG)
Publikationsdatum:
2020
ZDB Id:
2026156-1
