Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats

Publication date: 23 March 2016 Source:Neuroscience Letters, Volume 617 Author(s): Yaning Liu, Shangwu Wang, Shijian Luo, Zhendong Li, Fengyin Liang, Yanan Zhu, Zhong Pei, Ruxun Huang Glial cell line-derived neurotrophic factor (GDNF) is a potential therapeutic protein on a variety of central nervous system diseases including ischemic stroke. However, GDNF is a large molecule that cannot cross the blood–brain barrier (BBB), which is still intact in the early hours after stroke when neural rescue is possible. PEP-1 protein transduction domain can deliver protein cargo across the cell membrane and the BBB. In the present study, we generated a novel fusion protein PEP-1-GDNF and examined whether PEP-1-GDNF is protective in focal cerebral ischemia. PEP-1-GDNF (200μg/kg) or PBS was intravenously applied over 5min immediately after reperfusion of 90min transient middle cerebral artery occlusion (MCAO). After 28days, rats were deeply anesthetized and decapitated. Behavioral tests were performed during this period. The results showed that PEP-1-GDNF significantly reduced the infarct volume and improved behavioral function. Further, PEP-1-GDNF promoted the cell proliferation and differentiation in the dentate gyrus of the hippocampus and attenuated ischemia-induced learning and memory damage.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research