Abstract T P205: Thrombopoietin Reduces Brain Injury and Cognitive Impairment in Rodent Cerebrovascular Disease Models
Objectives: Thrombopoietin (TPO) reduces brain injury and sensory-motor deficits following stroke in the rat. TPO brain protection is mediated by vascular protection. TPO reduces stroke-induced inflammatory cytokines, matrix metalloproteinase’s and blood brain barrier injury. Here we demonstrate that TPO protects the brain and reduces vascular cognitive impairment in:  rat embolic stroke (+/- tissue plasminogen activator; tPA),  mouse suture-focal stroke, and  mouse chronic carotid stenosis-induced forebrain hypoperfusion.
Methods: Rats (Wistar) underwent embolic middle cerebral artery occlusion (MCAO). Vehicle, tPA (10 mg/kg, iv), TPO (0.1 μg/kg, iv) or TPO plus tPA were administered 2 hours post-stroke. Mice (C57Bl/6) underwent suture-MCAO or carotid artery stenosis-induced forebrain hypoperfusion and then received Vehicle or TPO (0.3 or 0.1 μg/kg, iv) at 1 hr or 1 day after surgery. Neurological deficits, complex learning and hemispheric infarct size were measured for 1-21 days post-surgery.
Results: In rat embolic stroke, tPA or TPO plus tPA improved stroke-induced neurological deficits significantly. Significant post-stroke-induced deficits in APA cognitive performance were improved 87.2±16.4% by TPO or 69.4±9.7% by TPO plus tPA, but not by tPA alone. In mouse suture-focal stroke, brain infarcts were reduced by 64.5±7.7% and neurological deficits were reduced by 90.3±6.4%. In mouse carotid artery stenosis-induced forebrain hypoperfusion a single administration of TPO 1 day after surgery improved APA performance 84.8+3.1% 3 weeks later (all p<0.01).
Conclusions: We have demonstrated TPO long-term protection and safety with and without tPA. TPO exhibits protection in mouse suture-focal and in mouse forebrain hypoperfusion-induced complex learning deficits. These data present multiple model and species work that supports the potential “multiple use” of TPO in the future.
- Vascular cognitive impairment
- Drug administration
- Cerebrovascular disorders
- Endovascular stroke treatment
- Vascular disease
Author Disclosures: D.M. Rosenbaum: None. J. Zhou: None. H. Zhang: None. J. Li: None. J. Zhuang: None. C. Poon: None. C. Poon: None. F.C. Barone: None.
- © 2014 by American Heart Association, Inc.