title: Small Interfering RNA Targeting Dickkopf-1 Contributes to Neuroprotection After Intracerebral Hemorrhage in Rats.
abstract: Excessive Dickkopf-1 (Dkk-1) plays a vital role in secondary brain injury following ischemic stroke and psychotic disease. However, it is unclear whether an increased expression of Dkk-1 occurred after intracerebral hemorrhage (ICH). The present study examined the potential role of Dkk-1 after ICH. ICH was induced by a single injection of autologous blood into the basal ganglia of rats. Dkk-1 protein levels in brain tissue and serum were detected by enzyme-linked immunosorbent assay after ICH. Rats were treated with small interfering RNA targeting Dkk-1 (siDkk-1) or vehicle following ICH. Behavioral deficits and brain water content were examined. Blood-brain barrier (BBB) integrity was detected by Evans blue extravasation and observed by transmission electron microscopy. Wnt-1 was evaluated by real-time RT-PCR. The tight junction protein zonula occludens-1 (ZO-1) was investigated by immunohistochemistry and Western blot assays. Serum level of Dkk-1 did not differ between the ICH and sham groups. However, the level of Dkk-1 in brain tissue was significantly increased at 24 and 72 h after ICH. BBB disruption and brain edema, as well as neurological deficits, were remarkably ameliorated by administration of siDkk-1. Moreover, siDkk-1 treatment significantly increased the transcription of Wnt-1 mRNA and upregulated the expression of ZO-1. These results provide the first evidence that siDkk-1 treatment is neuroprotective against secondary injury including brain edema and BBB permeability following ICH; the mechanism of neuroprotection may be associated with improvement of BBB integrity.
authors.affiliation: Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.|Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 the Jianshe East Road, Zhengzhou, Henan Province, 450052, People's Republic of China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 the Jianshe East Road, Zhengzhou, Henan Province, 450052, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 the Jianshe East Road, Zhengzhou, Henan Province, 450052, People's Republic of China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 the Jianshe East Road, Zhengzhou, Henan Province, 450052, People's Republic of China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 the Jianshe East Road, Zhengzhou, Henan Province, 450052, People's Republic of China. chyou666@hotmail.com.
authors.forename: Fuyou
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000628:therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D034622:RNA Interference; D000067492:RNAi Therapeutics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; C569044:Tjp1 protein, rat; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D062826:Zonula Occludens-1 Protein
keywords: Blood–brain barrier; Dickkopf-1; Intracerebral hemorrhage; Neuroprotection; Small interfering RNA