Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats. (23rd March 2016)

• Record Type: Journal Article
• Authors: Liu, Yaning; Wang, Shangwu; Luo, Shijian; Li, Zhendong; Liang, Fengyin; Zhu, Yanan; Pei, Zhong; Huang, Ruxun
• Is Part Of: Neuroscience letters. Volume 617(2016)
• Page Start: 150
• Page End: 155
• Publication Date: 2016-03-23
• Subjects: GDNF glial cell line-derived neurotrophic factor -- GFRα-1 GDNF-family receptorα-1 -- PTD protein transduction domain -- BBB blood–brain barrier -- DG dentate gyrus -- SVZ subventricular zone -- MCAO middle cerebral artery occlusion -- CCA common carotid artery -- ICA internal carotid artery -- ECA external carotid artery -- PBS phosphate buffered saline -- BrdU 5-bromo-2deoxyuridine; PEP-1-GDNF -- Protein transduction domain -- Infarct volume -- Neurogenesis -- Stroke; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.02.017
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: PEP-1-GDNF is neuroprotective by intravenous administration. PEP-1-GDNF reduces the infarct volume. PEP-1-GDNF promotes the neurogenesis in the hippocampus. PEP-1-GDNF improves the neurological function after stroke. Abstract: 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 (200 μg/kg) or PBS was intravenously applied over 5 min immediately after reperfusion of 90 min transient middle cerebral artery occlusion (MCAO). After 28 days, 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.