MRI of combination treatment of embolic stroke in rat with rtPA and atorvastatin.
To test the hypothesis that combination treatment of embolic stroke with rtPA and statins improves the efficacy of thrombolytic therapy in rats. Rats subjected to embolic MCA occlusion (MCAo) were randomized into control (n = 10) and treatment (n = 9) groups. Four hours after MCAo, a combination of rtPA and atorvastatin (treatment) or saline (control) was administered. MRI measurements were performed on all animals at 2 h, 24 h and 48 h after MCAo. The patency of cerebral microvessels was examined using fluorescent microscopy. MRI images showed complete blockage of the right MCA and a reduction of CBF in the territory supplied by the MCA 2 h after MCAo for all animals. By 48 h after stroke, MRI showed that the decreased lesion size, elevated CBF and increased incidence of recanalization were found in treated rats compared with the control rats. The combination treatment significantly increased microvascular patency (16.3 +/- 5.5% vs. 12.4 +/- 3.5%, of field-of-view) and reduced the infarct volume (23.1 +/- 9.6% vs. 38.8 +/- 13.3%, of hemisphere). These data demonstrate that the co-administration of rtPA and atorvastatin 4 h after ischemia is efficacious and is reflected by the MRI indices of recanalization of the MCA, reduction of secondary microvascular perfusion deficits and reduction of the ischemic lesion.
Ding
Guangliang
G
Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Jiang
Quan
Q
Li
Lian
L
Zhang
Li
L
Zhang
Zheng G
ZG
Panda
Swayamprava
S
Ewing
James R
JR
Chopp
Michael
M
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002545:Brain Ischemia / Q000473:pathology; D002560:Cerebrovascular Circulation; D003627:Data Interpretation, Statistical; D006538:Heptanoic Acids / Q000627:therapeutic use*; D020766:Intracranial Embolism / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D011994:Recombinant Proteins; D000069059:Atorvastatin; D010960:Plasminogen Activators