PMID- 18289020
OWN - NLM
STAT- MEDLINE
DCOM- 20090316
LR  - 20231213
IS  - 1875-5739 (Electronic)
IS  - 1567-2026 (Linking)
VI  - 5
IP  - 1
DP  - 2008 Feb
TI  - Nifedipine inhibits the progression of an experimentally induced cerebral 
      aneurysm in rats with associated down-regulation of NF-kappa B transcriptional 
      activity.
PG  - 37-45
AB  - Cerebral aneurysm (CA) causes a life-threatening subarachnoid hemorrhage. 
      However, no effective medical treatment to prevent the growth of CA is available. 
      Nifedipine, a widely used calcium antagonist, was shown to improve endothelial 
      function in various cardiovascular diseases. We examined whether nifedipine has a 
      protective effect on CA progression. CAs were experimentally induced in 
      Sprague-Dawley rats followed by intraperitoneal injection of either 10mg/kg of 
      nifedipine per day or vehicle. The size and media thickness of CAs were measured 
      one month after aneurysm induction. NF-kappa B (NF-kappaB) activity in aneurysmal 
      walls was assessed by immunohistochemistry for activated NF-kappaB p65 subunit 
      and electrophoretic mobility shift assay (EMSA). Expression of monocyte 
      chomoattractant protein-1 (MCP-1) and matrix metalloproteinase (MMP) -2 in 
      aneurysmal walls was examined by RT-PCR and immunohistochemistry. To examine 
      whether nifedipine has a suppressive effect on preexisting CAs, nifedipine 
      administration started at one month after aneurysm induction and pathological 
      changes were assessed at two months after aneurysm induction. Aneurysm size was 
      smaller and the media was thicker in the nifedipine-treated group even though 
      blood pressure was not different between groups. Nifedipine inhibited DNA binding 
      of NF-kappaB in aneurysmal walls. As regards MCP-1 expression and macrophage, 
      which is the main inflammatory cell in the aneurysmal walls, infiltration into 
      aneurysmal walls was decreased by nifedipine. Immunohistochemistry and gelatin 
      zymography showed that the expression and activity of MMP-2 was also reduced by 
      nifedipine. Furthermore, nifedipine significantly prevented the enlargement and 
      degeneration of aneurysmal walls of preexisting CAs. Nifedipine may be useful as 
      a medical drug for patients with CAs.
FAU - Aoki, Tomohiro
AU  - Aoki T
AD  - Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. tomoaoki@kuhp.kyoto-u.ac.jp
FAU - Kataoka, Hiroharu
AU  - Kataoka H
FAU - Ishibashi, Ryota
AU  - Ishibashi R
FAU - Nozaki, Kazuhiko
AU  - Nozaki K
FAU - Hashimoto, Nobuo
AU  - Hashimoto N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Neurovasc Res
JT  - Current neurovascular research
JID - 101208439
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Calcium Channel Blockers/*therapeutic use
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Down-Regulation/*drug effects
MH  - Electrophoretic Mobility Shift Assay/methods
MH  - Intracranial Aneurysm/*drug therapy/*enzymology/pathology
MH  - Macrophages/drug effects
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Nifedipine/*therapeutic use
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - NF-kappaB-Inducing Kinase
EDAT- 2008/02/22 09:00
MHDA- 2009/03/17 09:00
CRDT- 2008/02/22 09:00
PHST- 2008/02/22 09:00 [pubmed]
PHST- 2009/03/17 09:00 [medline]
PHST- 2008/02/22 09:00 [entrez]
AID - 10.2174/156720208783565663 [doi]
PST - ppublish
SO  - Curr Neurovasc Res. 2008 Feb;5(1):37-45. doi: 10.2174/156720208783565663.