Protective Effect of Exercise on Nerve Growth Factor in the Hippocampal CA1 Region Following Ischemic Stroke in Male Rat

Document Type : Original Article (s)

10.22122/jims.v39i615.13725

Abstract

Background: Brain ischemia causes irreversible structural and functional damages to specific parts of brain particularly the hippocampus. There are evidences that show exercise training may decrease the damages inflected on brain. The purpose of this research was to examine the effect of exercise training on nerve growth factor (NGF) in hippocampus CA1 region following cerebral ischemia stroke in male Wistar Rats.
Methods: 24 male Wistar rats weighing 250-300 g were randomly assigned into three groups including Sham, Ischemia/Control, and Ischemia/Exercise. The rats in the exercise groups ran on a rat treadmill for 45 minutes per day five days a week for 8 consecutive weeks. Common carotid artery occlusion procedure was employed for 45 minutes to induce ischemia. Cresyl violet (Nissl) was used to neuronal death, and ladder rung walking test was used to evaluate motor and functional recovery. In addition, NGF protein expression was assayed by immunohistochemistry.
Findings: Brain ischemia increased neuron death in CA1 region in hippocampus and impaired motor performance on the ladder rung task. In contrast, post-ischemic exercise considerably reduced neuron death and improved skilled motor performance. In addition, NGF protein expression was significantly higher in ischemic/exercise group than the ischemic/control group (P < 0.05).
Conclusion: When exercise is prescribed as a treatment and rehabilitation method after cerebral ischemia, it had significant effects on increasing NGF protein expression, and may reduce dead cells, and improve motor function.

Keywords


Knecht S, Hesse S, Oster P. Rehabilitation after stroke. Dtsch Arztebl Int 2011; 108(36): 600-6.
Antonow-Schlorke I, Ehrhardt J, Knieling M. Modification of the ladder rung walking task-new options for analysis of skilled movements. Stroke Res Treat 2013; 2013: 418627.
Stroke Unit Trialists' Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev 2013; (9): CD000197.
Luft AR, Macko RF, Forrester LW, Villagra F, Ivey F, Sorkin JD, et al. Treadmill exercise activates subcortical neural networks and improves walking after stroke: A randomized controlled trial. Stroke 2008; 39(12): 3341-50.
Kesner RP, Adelstein TB, Crutcher KA. Equivalent spatial location memory deficits in rats with medial septum or hippocampal formation lesions and patients with dementia of the Alzheimer's type. Brain Cogn 1989; 9(2): 289-300.
Moseley AM, Stark A, Cameron ID, Pollock A. Treadmill training and body weight support for walking after stroke. Stroke 2003; 34(12): 3006.
Mizutani K, Sonoda S, Yamada K, Beppu H, Shimpo K. Alteration of protein expression profile following voluntary exercise in the perilesional cortex of rats with focal cerebral infarction. Brain Res 2011; 1416: 61-8.
Ang ET, Wong PT, Moochhala S, Ng YK. Neuroprotection associated with running: Is it a result of increased endogenous neurotrophic factors? Neuroscience 2003; 118(2): 335-45.
Hassankhani A, Steinhelper ME, Soonpaa MH, Katz EB, Taylor DA, Andrade-Rozental A, et al. Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells. Dev Biol 1995; 169(1): 309-21.
Xing Y, Yang SD, Dong F, Wang MM, Feng YS, Zhang F. The beneficial role of early exercise training following stroke and possible mechanisms. Life Sci 2018; 198: 32-7.
Li F, Geng X, Khan H, Pendy JT, Jr., Peng C, Li X, et al. Exacerbation of brain injury by post-stroke exercise is contingent upon exercise initiation timing. Front Cell Neurosci 2017; 11: 311.
Shen J, Huber M, Zhao EY, Peng C, Li F, Li X, et al. Early rehabilitation aggravates brain damage after stroke via enhanced activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX). Brain Res 2016; 1648(Pt A): 266-76.
Erfani S, Khaksari M, Oryan S, Shamsaei N, Aboutaleb N, Nikbakht F. Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation. J Mol Neurosci 2015; 56(1): 237-43.
Shamsaei N, Erfani S, Fereidoni M, Shahbazi A. Neuroprotective Effects of exercise on brain edema and neurological movement disorders following the cerebral ischemia and reperfusion in rats. Basic Clin Neurosci 2017; 8(1): 77-84.
Metz GA, Whishaw IQ. The ladder rung walking task: A scoring system and its practical application. J Vis Exp 2009; (28): 1204.
Keith BJF, Paxinos G. Paxinos and Franklin's the mouse brain in stereotaxic coordinates, compact: The coronal plates and diagrams. 5th ed. San Diego, CA: Academic Press; 2019.
Kiernan J. Histological and histochemical methods: Theory and practice. 4th ed. Woodbury, NY: Cold Spring Harbor Laboratory Press; 2008.
Hofman F. Immunohistochemistry. Current Protocols in Immunology 2002; 49(1): 21.
Sugawara T, Lewen A, Noshita N, Gasche Y, Chan PH. Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. J Neurotrauma 2002; 19(1): 85-98.
Fu SH, Zhang HF, Yang ZB, Li TB, Liu B, Lou Z, et al. Alda-1 reduces cerebral ischemia/reperfusion injury in rat through clearance of reactive aldehydes. Naunyn Schmiedebergs Arch Pharmacol 2014; 387(1): 87-94.
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35(4): 495-516.
Dong Z, Bai Y, Wu X, Li H, Gong B, Howland JG, et al. Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Neuropharmacology 2013; 64: 65-73.
Metz GA, Antonow-Schlorke I, Witte OW. Motor improvements after focal cortical ischemia in adult rats are mediated by compensatory mechanisms. Behav Brain Res 2005; 162(1): 71-82.
Teixeira AL, Barbosa IG, Diniz BS, Kummer A. Circulating levels of brain-derived neurotrophic factor: Correlation with mood, cognition and motor function. Biomark Med 2010; 4(6): 871-87.
Xie Q, Cheng J, Pan G, Wu S, Hu Q, Jiang H, et al. Treadmill exercise ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting dendritic modification and synaptic plasticity via upregulating caveolin-1/VEGF signaling pathways. Exp Neurol 2019; 313: 60-78.
Pang Q, Zhang H, Chen Z, Wu Y, Bai M, Liu Y, et al. Role of caveolin-1/vascular endothelial growth factor pathway in basic fibroblast growth factor-induced angiogenesis and neurogenesis after treadmill training following focal cerebral ischemia in rats. Brain Res 2017; 1663: 9-19.
Koo HM, Lee SM, Kim MH. Spontaneous wheel running exercise induces brain recovery via neurotrophin-3 expression following experimental traumatic brain injury in rats. J Phys Ther Sci 2013; 25(9): 1103-7.
Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 2004; 20(10): 2580-90.
Tian S, Zhang Y, Tian S, Yang X, Yu K, Zhang Y, et al. Early exercise training improves ischemic outcome in rats by cerebral hemodynamics. Brain Res 2013; 1533: 114-21.
Zhang P, Xianglei J, Hongbo Y, Zhang J, Xu C. Neuroprotection of early locomotor exercise poststroke: Evidence from animal studies. Can J Neurol Sci 2015; 42(4): 213-20.
Gomez-Pinilla F, Dao L, So V. Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res 1997; 764(1-2): 1-8.
Zhang P, Yu H, Zhou N, Zhang J, Wu Y, Zhang Y, et al. Early exercise improves cerebral blood flow through increased angiogenesis in experimental stroke rat model. J Neuroeng Rehabil 2013; 10: 43.
Matsuda F, Sakakima H, Yoshida Y. The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats. Acta Physiol (Oxf) 2011; 201(2): 275-87.
Chang MC, Park CR, Rhie SH, Shim WH, Kim DY. Early treadmill exercise increases macrophage migration inhibitory factor expression after cerebral ischemia/reperfusion. Neural Regen Res 2019; 14(7): 1230-6.