Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke.
To dynamically investigate the long-term response of an ischemic lesion in rat brain to the administration of sildenafil, male Wistar rats subjected to embolic stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10 mg/kg administered subcutaneously 24-h after stroke and daily for an additional 6 days. Magnetic resonance images were acquired and functional performance was measured in all animals at 1 day, 2 days and weekly for 6 weeks post-stroke. All rats were sacrificed 6 weeks after stroke and endothelial barrier antigen immunostaining was employed for morphological analysis and quantification of cerebral vessels. Map-ISODATA was computed from T(1), T(2) and T(1sat) maps. ISODATA derived tissue signatures characterize the degree of ischemic injury. Based on the map-ISODATA calculated at 6 weeks, the ischemic lesion for each animal was divided into two specific regions, the ischemic boundary and ischemic core. The temporal profiles of cerebral blood flow (CBF) and tissue signature were retrospectively tracked in these two regions and were compared with histological evaluation and functional outcome. After 1 week of sildenafil treatment, the ischemic lesion exhibited two significantly different regions, with higher CBF level and correspondingly, lower tissue signature value in the boundary region than in the core region. Sildenafil treatment did not significantly reduce the lesion size, but did enhance angiogenesis. Functional performance was significantly increased after sildenafil treatment compared with the control group. Administration of sildenafil to rats with embolic stroke enhances angiogenesis and selectively increases the CBF level in the ischemic boundary, and improves neurological functional recovery compared to saline-treated rats.
Li
Lian
L
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Jiang
Quan
Q
Zhang
Li
L
Ding
Guangliang
G
Gang Zhang
Zheng
Z
Li
Qingjiang
Q
Ewing
James R
JR
Lu
Mei
M
Panda
Swayamprava
S
Ledbetter
Karyn A
KA
Whitton
Polly A
PA
Chopp
Michael
M
D000818:Animals; D000954:Antigens, Surface / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D002542:Intracranial Embolism and Thrombosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D000068677:Sildenafil Citrate; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D000954:Antigens, Surface; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; C114781:endothelial barrier antigen, rat; D000068677:Sildenafil Citrate