title: A new clinically relevant model for intracranial atherosclerosis in rats.
abstract: BACKGROUND
  Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We developed a new rat model to study intracranial atherosclerosis.
  
  
  METHODS
  Twelve-week-old male Sprague-Dawley rats were divided into a control (on a maintain diet) and a high-cholesterol group (on a daily 1% cholesterol diet) for up to 6 weeks. During the first two weeks, NG-nitro-L-arginine methylester (L-NAME, 3 mg/mL) was added to the drinking water in the high-cholesterol group to induce intimal changes making the rats susceptible to atherosclerosis. Blood lipids, including low-density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG), and high-density lipoprotein (HDL), were measured after 3 and 6 weeks. Histological sections of the brains, including internal carotid artery (ICA), middle cerebral artery (MCA), and basilar artery (BA), were prepared to study intracranial artery morphometry and intimal thickening. The levels of CD68, an inflammatory marker, within the vessel walls as determined by immunohistochemistry were also measured.
  
  
  RESULTS
  The high-cholesterol diet increased the levels of classic blood markers of atherosclerosis, LDL, CHO, and TG as well as decreased HDL, which became progressively more intensive with time. Rats showed increased intimal thickening in the ICA, MCA, and BA. This protocol also increased the levels of CD68 immunoreactivity within the vessel walls.
  
  
  CONCLUSIONS
  A rat model of intracranial atherosclerosis was effectively developed by high-cholesterol diet and L-NAME administration. This clinically relevant model would be beneficial for studying ICAS.
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Shen
authors.affiliation: b Department of Neurological Surgery , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: James
authors.initials: J
authors.lastname: Stevenson
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.|b Department of Neurological Surgery , Wayne State University School of Medicine , Detroit , MI , USA.|c Department of Neurology , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Geng
authors.affiliation: d Department of Pathology , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Yang
authors.affiliation: e Department of Clinical Laboratory , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Changbin
authors.initials: C
authors.lastname: Yin
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Fengwu
authors.initials: F
authors.lastname: Li
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Wang
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.|c Department of Neurology , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Huishan
authors.initials: H
authors.lastname: Du
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
authors.affiliation: a China-America Institute of Neuroscience , Beijing Luhe Hospital, Capital Medical University , Beijing , China.|b Department of Neurological Surgery , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001488:Basilar Artery / Q000473:pathology; D001835:Body Weight; D002343:Carotid Artery, Internal / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004435:Eating; D004791:Enzyme Inhibitors / Q000633:toxicity*; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology; D008055:Lipids / Q000097:blood*; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004791:Enzyme Inhibitors; D008055:Lipids; D019331:NG-Nitroarginine Methyl Ester; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: BA, basilar artery; Basilar artery (BA) and Internal carotid artery (ICA); CD68; HDL; High-cholesterol diet; High-density lipoproteins; ICA, internal carotid artery; ICAS, intracranial atherosclerotic stenosis; Intracranial atherosclerosis; LDL, low-density lipoprotein; MCA, middle cerebral artery; Middle cerebral artery (MCA); NG-nitro-L-arginine methylester; TG, triglycerides