Progesterone increases circulating endothelial progenitor cells and induces neural regeneration after traumatic brain injury in aged rats.

Abstract

Vascular remodeling plays a key role in neural regeneration in the injured brain. Circulating endothelial progenitor cells (EPCs) are a mediator of the vascular remodeling process. Previous studies have found that progesterone treatment of traumatic brain injury (TBI) decreases cerebral edema and cellular apoptosis and inhibits inflammation, which in concert promote neuroprotective effects in young adult rats. However, whether progesterone treatment regulates circulating EPC level and fosters vascular remodeling after TBI have not been investigated. In this study, we hypothesize that progesterone treatment following TBI increases circulating EPC levels and promotes vascular remodeling in the injured brain in aged rats. Male Wistar 20-month-old rats were subjected to a moderate unilateral parietal cortical contusion injury and were treated with or without progesterone (n=54/group). Progesterone was administered intraperitoneally at a dose of 16mg/kg at 1 h post-TBI and was subsequently injected subcutaneously daily for 14 days. Neurological functional tests and immnunostaining were performed. Circulating EPCs were measured by flow cytometry. Progesterone treatment significantly improved neurological outcome after TBI measured by the modified neurological severity score, Morris Water Maze and the long term potentiation in the hippocampus as well as increased the circulating EPC levels compared to TBI controls (p<0.05). Progesterone treatment also significantly increased CD34 and CD31 positive cell number and vessel density in the injured brain compared to TBI controls (p<0.05). These data indicate that progesterone treatment of TBI improves multiple neurological functional outcomes, increases the circulating EPC level, and facilitates vascular remodeling in the injured brain after TBI in aged rats.

• Authors: Zhanying Li, Bin Wang, Zhisheng Kan, Baoliang Zhang, Zhuo Yang, Jieli Chen, Dong Wang, Huijie Wei, Jian-ning Zhang, Rongcai Jiang
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 29 Issue 2 Pg. 343-53 (Jan 20 2012) ISSN: 1557-9042 [Electronic] United States
• PMID: 21534727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Progesterone

Topics

• Animals
• Brain Injuries (pathology, physiopathology, therapy)
• Cell Differentiation (physiology)
• Disease Models, Animal
• Endothelial Cells (pathology, physiology)
• Male
• Mesenchymal Stem Cells (pathology, physiology)
• Neurogenesis (physiology)
• Neuroprotective Agents (therapeutic use)
• Progesterone (therapeutic use)
• Rats
• Rats, Wistar