Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke-evaluating the impact of therapeutic time points on prognostic outcomes.
BACKGROUND
This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS).


METHODS AND RESULTS
Adult male SD rats (n = 70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2 × 106 cells/by LICA administration 3 h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS), and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2, and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all P < 0.0001). By day 60, the endothelial cell markers at protein and cellular levels and number of small vessels exhibited an opposite pattern of BIV among the groups (all P < 0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy, and apoptosis were highest in group 2, lowest in group 1, and progressively increased from groups 3 to 7 (all P < 0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all P < 0.0001).


CONCLUSION
Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.
['Lin|Kun-Chen|KC|', 'Chai|Han-Tan|HT|', 'Chen|Kuan-Hung|KH|', 'Sung|Pei-Hsun|PH|', 'Chiang|John Y|JY|', 'Shao|Pei-Lin|PL|', 'Huang|Chi-Ruei|CR|', 'Li|Yi-Chen|YC|', 'Ko|Sheung-Fat|SF|', 'Yip|Hon-Kan|HK|0000-0002-6305-5717']
D000818:Animals D002545:Brain Ischemia D066026:Endothelial Progenitor Cells D000083242:Ischemic Stroke D008297:Male D011379:Prognosis D051381:Rats D017207:Rats, Sprague-Dawley D012377:Rodentia D020521:Stroke
Endothelial progenitor cells Ischemic stroke Neurological function Angiogenesis