Effect of Modified Constraint-induced Movement Therapy on Neurotransmitter Levels of Motor Cortex in Cerebral Ischemia-Reperfusion Injured Rats

GAO Bei-yao, XU Dong-sheng, XIE Bei-jing, LIU Pei-le, LI Ce, DU Liang, HUA Yan, HU Jian, BAI Yu-lon

Abstract

To study the effect and mechanism of modified constraint-induced movement therapy (mCIMT) on motor function recovery in cerebral ischemia-reperfusion rats.  Methods  The rats were randomly divided into the control group and the mCIMT group, with 12 rats in each group. The left middle cerebral artery occlusion (MCAO) model was established by the Longa suture method. In the mCIMT group, the rats started continuous training for 14 d on the 7th day after modeling. The unaffected limb was tied to the chest with elastic bandages, and the affected limb was trained in the compulsory runner equipment. In the control group, rats moved freely in the cage. The body mass of rats was recorded within 20 d after modeling, and behavior was assessed by the foot-fault test. Some of the rats were euthanized 18 d after modeling, and high performance liquid chromatography (HPLC) was used to detect monoamine neurotransmitters (5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIVV), homovanillic acid (HVA) ), and amino acid neurotransmitters (glutamic acid (Glu), asparaginic acid (ASP), glutamine (Gln), glycine (Gly), taurine (Tau), gamma aminobutyric acid (GABA) ) in the motor cortex and striatum, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of total P70 ribosomal protein S6 kinase (p70s6k) and p70s6k phosphorylated protein (p-p70s6k) in motor cortex and striatum, respectively.  Results  Compared with the control group, the body mass of rats in the mCIMT group was comparable (P>0.05) within 21 d after modeling, foot-fault rate of the mCIMT group was significantly lower at 17 d after modeling (P<0.05). At 18 d after modeling, compared with the control group, the level of 5-HIVV in the motor cortex increased significantly (P<0.05), and the relative content of amino acid neurotransmitters (the ratio of Glu) in the motor cortex including Gln, Gly, Tau and GABA to Glu increased significantly (P<0.05 or P<0.01) except for decreased ASP/Glu (P<0.05). Moreover, compared with the control group, the expression of p-p70s6k in the motor cortex of the mCIMT was significantly decreased (P<0.05). There were no significant differences in monoamine neurotransmitters and amino acid neurotransmitters in the striatum between two groups (P>0.05).  Conclusion  mCIMT improved the motor function of MCAO rats, and the mechanism might be related to the increase of amino acid neurotransmitters and 5-HIVV and decrease of p-p70s6k expression in the motor cortex.

 

Keywords: Modified constraint induced movement therapy, Cerebral ischemia reperfusion injury, Amino acid neurotransmitters, Monoamine neurotransmitters, p70s6k

 

Full Text:

PDF


References


FEIGIN V L， ROTH G A， NAGHAVI M， et al. Global burden of stroke and risk factors in 188 countries, during 1990−2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol，2016，15(9): 913–924.

LANGHORNE P， O'DONNELL M J， CHIN S L， et al. Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study. Lancet，2018， 391(10134): 2019–2027.

BARZEL A， KETELS G， STARK A， et al. Home-based constraint-induced movement therapy for patients with upper limb dysfunction after stroke (HOMECIMT): a cluster-randomised, controlled trial. Lancet Neurol，2015，14(9): 893–902.

KWAKKEL G， VEERBEEK J M， VAN WEGEN E E， et al. Constraint-induced movement therapy after stroke. Lancet Neurol，2015，14(2): 224–234.

ZHAO S， ZHAO M， XIAO T， et al. Constraint-induced movement therapy overcomes the intrinsic axonal growth-inhibitory signals in stroke rats. Stroke，2013，44(6): 1698–1705.

LONGA E Z， WEINSTEIN P R， CARLSON S， et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke，1989，20(1): 84–91.

ZHANG B， HE Q， LI Y Y， et al. Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats. Neural Regen Res，2015，10(12): 2004–2010.

ZHU H， WANG N， YAO L， et al. Moderate UV exposure enhances learning and memory by promoting a novel glutamate biosynthetic pathway in the brain. Cell，2018，173(7): 1716–1727.

TANG S Y， POWELL E M， ZHU W J， et al. Alter forebrain functional connectivity and neurotransmission in a kinase-inactive met mouse model of ausism. Mol Imaging， 2019， 18:1536012118821034[2020-03-12]. http://doi.org/10.1177/1536012118821034.

GAO B， XU D， LIU P， et al. Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion. Neural Regen Res，2020， 15(6): 1045–1057.

WAGNER M J， KIM T H， SAVALL J， et al. Cerebellar granule cells encode the expectation of reward. Nature，2017，544(7648): 96–100.

CIRANNA L. Serotonin as a modulator of glutamate- and GABA-mediated neurotransmission: implications in physiological functions and in pathology. Curr Neuropharmacol，2006，4(2): 101–114.

YAN X， JIANG E， WENG H R. Activaton of toll like receptor 4 attenuates GABA synthesis and postsynaptic GABA receptor activities in the spinal dorsal horn via releasing interleukin-1 beta. J Neuroinflammation， 2015， 12: 222[2020-03-12]. https://doi.org/ 10.1186/s12974-014-0222-3.

BOKA G， ANGLADE P， WALLACH D， et al. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease. Neurosci Lett，1994，172(1/2): 151–154.

SERAFINI G， POMPILI M， ELENA SERETTI M， et al. The role of inflammatory cytokines in suicidal behavior: a systematic review. Eur Neuropsychopharmacol，2013，23(12): 1672–1686.

PEREA G， NAVARRETE M， ARAQUE A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci， 2009，32(8): 421–431.

BAK L K， SCHOUSBOE A， WAAGEPETERSEN H S. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem，2006，98(3): 641–653.

CHAUDHRY F A， REIMER R J， EDWARDS R H. The glutamine commute. J Cell Biol，2002，157(3): 349–355.

DANBOLT N C. Glutamate uptake. Prog Neurobiol，2001，65(1): 1–105.


Refbacks

  • There are currently no refbacks.