Bis(propyl)-cognitin potentiates rehabilitation of treadmill exercise after a transient focal cerebral ischemia, possibly via inhibiting NMDA receptor and regulating VEGF expression

Zheng Ke; Shengquan Hu; Wei Cui; Jing Sun; Shaojie Zhang; Shinghung Mak; Jiajun Wang; Jing Tang; Yuanping Pang; Yifan Han; Kaiyu Tong

doi:10.1016/j.neuint.2019.04.016

Bis(propyl)-cognitin potentiates rehabilitation of treadmill exercise after a transient focal cerebral ischemia, possibly via inhibiting NMDA receptor and regulating VEGF expression

Neurochem Int. 2019 Sep:128:143-153. doi: 10.1016/j.neuint.2019.04.016. Epub 2019 Apr 26.

Authors

Zheng Ke¹, Shengquan Hu², Wei Cui², Jing Sun¹, Shaojie Zhang¹, Shinghung Mak², Jiajun Wang², Jing Tang³, Yuanping Pang³, Yifan Han⁴, Kaiyu Tong⁵

Affiliations

¹ Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong.
² Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
³ Mayo Cancer Center, Department of Pharmacology, Mayo Clinic, Rochester, MN, USA.
⁴ Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong. Electronic address: bcyfhan@polyu.edu.hk.
⁵ Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong; Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong. Electronic address: kytong@cuhk.edu.hk.

PMID: 31034915
DOI: 10.1016/j.neuint.2019.04.016

Abstract

Combination therapies may have greater efficacy compared with monotherapy in treating stroke. We investigated the molecular mechanisms by which the combination of bis(propyl)-cognitin, an uncompetitive antagonist of NMDA receptor, and treadmill exercise promote rehabilitation after ischemic stroke. Rats were distributed into 3 treatment groups: infarct/bis(propyl)-cognitin(drug only group, DO); infarct/treadmill exercise(exercise only group, EO); infarct/bis(propyl)-cognitin + treadmill exercise (drug + exercise group, DE). The DE group had further separated to 3 sub-groups to investigate the effects achieved by different time for drug administration (60 min before stroke (DE-60 m), 15 min (DE+15 m) and 60 min (DE+60 m) after stroke). Although all infarct groups improved over time, the combination of bis(propyl)-cognitin and treadmill exercise effectively enhanced motor recovery during 14-day intervention. Early drug intervention has a best recovery result, the DE+15 m group with drug intervention at 15-min after stroke had better motor recovery than DE+60 m, DO, EO and control groups. Both bis(propyl)-cognitin and treadmill exercise significantly elevated brain VEGF expression and decreased brain infarct volume at 14 day post-ischemia. Our study reveals that bis(propyl)-cognitin potentiated rehabilitation of treadmill exercise after ischemic stroke, possibly via regulating brain VEGF expression, indicating that the combination of NMDA receptor antagonists and exercise might be useful for stroke rehabilitation.

Keywords: Exercise; Ischemia; Motor recovery; Stroke; VEGF; bis(propyl)-cognitin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Ischemia / drug therapy*
Brain Ischemia / metabolism
Brain Ischemia / rehabilitation*
Exercise Test / drug effects*
Exercise Test / methods
Gene Expression
Male
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism
Tacrine / analogs & derivatives*
Tacrine / pharmacology
Tacrine / therapeutic use
Vascular Endothelial Growth Factor A / biosynthesis*
Vascular Endothelial Growth Factor A / genetics

Substances

Receptors, N-Methyl-D-Aspartate
Vascular Endothelial Growth Factor A
bis(propyl)cognitin
vascular endothelial growth factor A, rat
Tacrine