Abstract

 
 
 
 Purpose: To investigate the protective effects of Compound Tongluo decoction (CTD)on neurological function in rats, and the mechanism involved in its angiogenesis-promoting effect.
 Methods: Rats were arbitrarily assigned to sham group, permanent middle cerebral artery infarction (pMCAO) group, and PMCAO+CTD group (pMCAO plus 7-day oral treatment with CTD). Neurological deficit scores and volume of stroke-damaged areas were measured after 7 days of treatment. The levels of bone marrow-derived endothelial progenitor cells (BMEPCs) in serum and brain tissues were determined by flow cytometry and immunofluorescence. The expression levels of sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), and angiopoietin-1(Ang-1) at infarct sites and in BMEPCs were quantitated using western blot assay.
 Results: The results showed that CTD markedly ameliorated neurological deficit, reduced volume of affected areas, and promoted the production and homing of BMEPCs. Moreover, CTD upregulated Shh, VEGF and Ang-1expressions at ischemic sites and EPCs, but promoted the proliferation and metastasis of EPCs. The CTD-induced changes were significantly suppressed by Shh inhibitor cyclopamine (CP).
 Conclusion: These results demonstrate that CTD promotes angiogenesis after cerebral infarction, probably by stimulating Shh signaling and triggering production and homing of EPCs, thereby providing neuroprotection against cerebral infarction. Thus, CTD is a potential neuroprotective agent against cerebral infarction in humans.
 
 
 
Highlights
Stroke is a neurological disease associated with high morbidity, mortality, and disability, and it imposes tremendous health and economic burden on the family and society
The results showed that stroke volume was markedly reduced in permanent middle cerebral artery infarction (pMCAO)+Compound Tongluo decoction (CTD) group, relative to pMCAO group (p < 0.05; Figure 1 A)
The neurological function of rats with cerebral infarction was determined at multiple time points to ascertain the effect of CTD on neurobehavioral ability
Summary
Stroke is a neurological disease associated with high morbidity, mortality, and disability, and it imposes tremendous health and economic burden on the family and society. Endothelial progenitor cells (EPCs) derived from pluripotent stem cells are promising targets for angiogenesis, re-endothelialization, and blood vessel repair in various diseases. They are expected to be useful for revascularization due to their clinical values [3]. Evidence have shown that EPCs differentiate into mature endothelial cells (ECs) which play vital roles in angiogenesis after cerebral ischemic injury [4]. They offer protection against endothelial injury and dysfunctional endothelium by directly incorporating themselves into newly formed blood vessels or stimulating pro-angiogenic growth factors or cytokines [5]
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