title: Human tissue kallikrein ameliorates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage.
abstract: OBJECTIVE
  Cerebral vasospasm (CVS) and early brain injury are major causes of morbidity and mortality following subarachnoid hemorrhage (SAH). We investigated the efficiency of human tissue kallikrein (HTK) to prevent CVS in a rabbit model of SAH.
  
  
  METHODS
  Forty-eight Japanese white rabbits were randomly divided into four groups (n = 12 each): control (sham-operated), SAH, SAH + phosphate-buffered saline (PBS, vehicle), and SAH + HTK. Basilar artery (BA) diameters were measured by three-dimensional computed tomography angiography at three time points. Endothelin-1 (ET-1) and nitric oxide (NO) levels in the cerebrospinal fluid (CSF) were assayed 24 h before and 5 and 7 days after SAH. After the last measurement, the animals were killed, and endothelial cell apoptosis was assessed. Bax and Bcl-2 levels in the BA were measured by western blotting.
  
  
  RESULTS
  HTK was found to significantly reduce CVS following SAH in rabbits. Inverse changes were observed in ET-1 and NO levels in the CSF collected from the SAH group. HTK increased levels of NO, which has a vasodilatory effect, but did not affect levels of ET-1, which has a vasoconstrictive effect. CTA revealed that HTK treatment significantly increased BA diameter. Moreover, HTK treatment reduced the number of apoptotic cells following SAH, presumably by increasing and decreasing Bcl-2 and Bax expression, respectively.
  
  
  CONCLUSIONS
  HTK ameliorated CVS and inhibited apoptosis in the BA in a rabbit model of SAH.
authors.affiliation: 1 Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shanxi 710004, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Yunchang
authors.forename: Dai
authors.initials: D
authors.lastname: Qinxue
authors.forename: Ji
authors.initials: J
authors.lastname: Binbin
authors.forename: He
authors.initials: H
authors.lastname: Xin
authors.forename: Yang
authors.initials: Y
authors.lastname: Lili
authors.forename: Chen
authors.initials: C
authors.lastname: Linbi
authors.forename: Geng
authors.initials: G
authors.lastname: Wujun
authors.forename: Zhang
authors.initials: Z
authors.lastname: Pengbo
authors.forename: Wang
authors.initials: W
authors.lastname: Junlu
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging / Q000473:pathology; D003029:Coagulants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000134:cerebrospinal fluid; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D007610:Kallikreins / Q000627:therapeutic use*; D009460:Neurologic Examination; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D011817:Rabbits; D011859:Radiography; D018709:Statistics, Nonparametric; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D015898:Tomography Scanners, X-Ray Computed; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology
chemical_list: D003029:Coagulants; D019332:Endothelin-1; D009569:Nitric Oxide; D007610:Kallikreins
keywords: Apoptosis; Cerebral vasospasm; Cerebrovascular endothelial cell; Endothelin-1; Human tissue kallikrein; Nitric oxide; Subarachnoid hemorrhage