Effects of long‑term post‑ischemic treadmill exercise on gliosis in the aged gerbil hippocampus induced by transient cerebral ischemia

Ahn,Ji Hyeon; Shin,Myoung Cheol; Park,Joon Ha; Kim,In Hye; Cho,Jeong‑Hwi; Lee,Tae‑Kyeong; Lee,Jae‑Chul; Chen,Bai Hui; Shin,Bich Na; Tae,Hyun‑Jin; Park,Jinseu; Choi,Soo Young; Lee,Yun Lyul; Kim,Dae Won; Kim,Yang Hee; Won,Moo‑Ho; Cho,Jun Hwi

doi:10.3892/mmr.2017.6485

Effects of long‑term post‑ischemic treadmill exercise on gliosis in the aged gerbil hippocampus induced by transient cerebral ischemia

Authors:
- Ji Hyeon Ahn
- Myoung Cheol Shin
- Joon Ha Park
- In Hye Kim
- Jeong‑Hwi Cho
- Tae‑Kyeong Lee
- Jae‑Chul Lee
- Bai Hui Chen
- Bich Na Shin
- Hyun‑Jin Tae
- Jinseu Park
- Soo Young Choi
- Yun Lyul Lee
- Dae Won Kim
- Yang Hee Kim
- Moo‑Ho Won
- Jun Hwi Cho
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Affiliations: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Kangnung‑Wonju National University, Gangneung, Gangwon 25457, Republic of Korea, Department of Surgery, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
Published online on: April 19, 2017 https://doi.org/10.3892/mmr.2017.6485
Pages: 3623-3630
Copyright: © Ahn et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Therapeutic exercise is an integral component of the rehabilitation of patients who have suffered a stroke. The objective of the present study was to use immunohistochemistry to investigate the effects of post‑ischemic exercise on neuronal damage or death and gliosis in the aged gerbil hippocampus following transient cerebral ischemia. Aged gerbils (male; age, 22‑24 months) underwent ischemia and were subjected to treadmill exercise for 1 or 4 weeks. Neuronal death was detected in the stratum pyramidale of the hippocampal CA1 region and in the polymorphic layer of the dentate gyrus using cresyl violet and Fluoro‑Jade B histofluorescence staining. No significant difference in neuronal death was identified following 1 or 4 weeks of post‑ischemic treadmill exercise. However, post‑ischemic treadmill exercise affected gliosis (the activation of astrocytes and microglia). Glial fibrillary acidic protein‑immunoreactive astrocytes and ionized calcium binding adaptor molecule 1‑immunoreactive microglia were activated in the CA1 and polymorphic layer of the dentate gyrus of the group without treadmill exercise. Conversely, 4 weeks of treadmill exercise significantly alleviated ischemia‑induced astrocyte and microglial activation; however, 1 week of treadmill exercise did not alleviate gliosis. These findings suggest that long‑term post‑ischemic treadmill exercise following transient cerebral ischemia does not influence neuronal protection; however, it may effectively alleviate transient cerebral ischemia‑induced astrocyte and microglial activation in the aged hippocampus.

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1	Kirino T: Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239:57–69. 1982. View Article : Google Scholar : PubMed/NCBI
2	Lin CS, Polsky K, Nadler JV and Crain BJ: Selective neocortical and thalamic cell death in the gerbil after transient ischemia. Neuroscience. 35:289–299. 1990. View Article : Google Scholar : PubMed/NCBI
3	Petito CK, Torres-Munoz J, Roberts B, Olarte JP, Nowak TS Jr and Pulsinelli WA: DNA fragmentation follows delayed neuronal death in CA1 neurons exposed to transient global ischemia in the rat. J Cereb Blood Flow Metab. 17:967–976. 1997. View Article : Google Scholar : PubMed/NCBI
4	Horn M and Schlote W: Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol. 85:79–87. 1992. View Article : Google Scholar : PubMed/NCBI
5	Lee CH, Yoo KY, Choi JH, Park OK, Hwang IK, Kim SK, Kang IJ, Kim YM and Won MH: Neuronal damage is much delayed and microgliosis is more severe in the aged hippocampus induced by transient cerebral ischemia compared to the adult hippocampus. J Neurol Sci. 294:1–6. 2010. View Article : Google Scholar : PubMed/NCBI
6	Tamagaki C, Murata A, Asai S, Takase K, Gonno K, Sakata T and Kinoshita T: Age-related changes of cornu ammonis 1 pyramidal neurons in gerbil transient ischemia. Neuropathology. 20:221–227. 2000. View Article : Google Scholar : PubMed/NCBI
7	Bernal GM and Peterson DA: Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells. Aging cell. 10:466–482. 2011. View Article : Google Scholar : PubMed/NCBI
8	Gehrmann J, Bonnekoh P, Miyazawa T, Hossmann KA and Kreutzberg GW: Immunocytochemical study of an early microglial activation in ischemia. J Cereb Blood Flow Metab. 12:257–269. 1992. View Article : Google Scholar : PubMed/NCBI
9	Norden DM and Godbout JP: Review: Microglia of the aged brain: Primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol. 39:19–34. 2013. View Article : Google Scholar : PubMed/NCBI
10	Choi JH and Won MH: Microglia in the normally aged hippocampus. Lab Anim Res. 27:181–187. 2011. View Article : Google Scholar : PubMed/NCBI
11	Nedergaard M and Dirnagl U: Role of glial cells in cerebral ischemia. Glia. 50:281–286. 2005. View Article : Google Scholar : PubMed/NCBI
12	Lai AY and Todd KG: Microglia in cerebral ischemia: Molecular actions and interactions. Can J Physiol Pharmacol. 84:49–59. 2006. View Article : Google Scholar : PubMed/NCBI
13	Kwakkel G, Van Peppen R, Wagenaar RC, Dauphinee S Wood, Richards C, Ashburn A, Miller K, Lincoln N, Partridge C, Wellwood I and Langhorne P: Effects of augmented exercise therapy time after stroke: a meta-analysis. Stroke. 35:2529–2539. 2004. View Article : Google Scholar : PubMed/NCBI
14	Zhang P, Zhang Q, Pu H, Wu Y, Bai Y, Vosler PS, Chen J, Shi H, Gao Y and Hu Y: Very early-initiated physical rehabilitation protects against ischemic brain injury. Front Biosci (Elite Ed). 4:2476–2489. 2012.PubMed/NCBI
15	Chen MF, Huang TY, Kuo YM, Yu L, Chen HI and Jen CJ: Early postinjury exercise reverses memory deficits and retards the progression of closed-head injury in mice. J Physiol. 591:985–1000. 2013. View Article : Google Scholar : PubMed/NCBI
16	Fang KM, Cheng FC, Huang YL, Chung SY, Jian ZY and Lin MC: Trace element, antioxidant activity, and lipid peroxidation levels in brain cortex of gerbils after cerebral ischemic injury. Biol Trace Elem Res. 152:66–74. 2013. View Article : Google Scholar : PubMed/NCBI
17	Liu YR, Lei RY, Wang CE, Zhang BA, Lu H, Zhu HC and Zhang GB: Effects of catalpol on ATPase and amino acids in gerbils with cerebral ischemia/reperfusion injury. Neurol Sci. 35:1229–1233. 2014. View Article : Google Scholar : PubMed/NCBI
18	Shcherbak NS, Galagudza MM, Ovchinnikov DA, Kuzmenkov AN, Yukina GY, Barantsevich ER, Tomson VV and Shlyakhto EV: Activity of succinate dehydrogenase in the neocortex and hippocampus of Mongolian gerbils with ischemic and reperfusion brain injury. Bull Exp Biol Med. 155:14–17. 2013. View Article : Google Scholar : PubMed/NCBI
19	Wang W, Wang T, Feng WY, Wang ZY, Cheng MS and Wang YJ: Ecdysterone protects gerbil brain from temporal global cerebral ischemia/reperfusion injury via preventing neuron apoptosis and deactivating astrocytes and microglia cells. Neurosci Res. 81(82): 21–29. 2014. View Article : Google Scholar : PubMed/NCBI
20	Ahn JH, Choi JH, Park JH, Kim IH, Cho JH, Lee JC, Koo HM, Hwangbo G, Yoo KY, Lee CH, et al: Long-term exercise improves memory deficits via restoration of myelin and microvessel damage, and enhancement of neurogenesis in the aged gerbil hippocampus after ischemic stroke. Neurorehabil Neural Repair. 30:894–905. 2016. View Article : Google Scholar : PubMed/NCBI
21	Sim YJ, Kim H, Kim JY, Yoon SJ, Kim SS, Chang HK, Lee TH, Lee HH, Shin MC, Shin MS and Kim CJ: Long-term treadmill exercise overcomes ischemia-induced apoptotic neuronal cell death in gerbils. Physiol Behav. 84:733–738. 2005. View Article : Google Scholar : PubMed/NCBI
22	Sim YJ, Kim SS, Kim JY, Shin MS and Kim CJ: Treadmill exercise improves short-term memory by suppressing ischemia-induced apoptosis of neuronal cells in gerbils. Neurosci Lett. 372:256–261. 2004. View Article : Google Scholar : PubMed/NCBI
23	Lee MH, Kim H, Kim SS, Lee TH, Lim BV, Chang HK, Jang MH, Shin MC, Shin MS and Kim CJ: Treadmill exercise suppresses ischemia-induced increment in apoptosis and cell proliferation in hippocampal dentate gyrus of gerbils. Life Sci. 73:2455–2465. 2003. View Article : Google Scholar : PubMed/NCBI
24	Ahn JH, Choi JH, Kim JS, Lee HJ, Lee CH, Yoo KY, Hwang IK, Lee YL, Shin HC and Won MH: Comparison of immunoreactivities in 4-HNE and superoxide dismutases in the cervical and the lumbar spinal cord between adult and aged dogs. Exp Gerontol. 46:703–708. 2011.PubMed/NCBI
25	Candelario-Jalil E, Alvarez D, Merino N and León OS: Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils. Neurosci Res. 47:245–253. 2003. View Article : Google Scholar : PubMed/NCBI
26	Sugawara T, Lewén A, Noshita N, Gasche Y and Chan PH: Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. J Neurotrauma. 19:85–98. 2002. View Article : Google Scholar : PubMed/NCBI
27	Li DQ, Bao YM, Li Y, Wang CF, Liu Y and An LJ: Catalpol modulates the expressions of Bcl-2 and Bax and attenuates apoptosis in gerbils after ischemic injury. Brain Res. 1115:179–185. 2006. View Article : Google Scholar : PubMed/NCBI
28	Takagi N: Pathology and strategies for the treatment of ischemic brain injury. Yakugaku Zasshi. 129:1215–1219. 2009.(In Japanese). View Article : Google Scholar : PubMed/NCBI
29	Ahn JH, Shin BN, Park JH, Kim IH, Cho JH, Chen B, Lee TK, Tae HJ, Lee JC, Cho JH, et al: Long-term observation of neuronal degeneration and microgliosis in the gerbil dentate gyrus after transient cerebral ischemia. J Neurol Sci. 363:21–26. 2016. View Article : Google Scholar : PubMed/NCBI
30	Danton GH and Dietrich WD: Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol. 62:127–136. 2003. View Article : Google Scholar : PubMed/NCBI
31	Stoll G and Jander S: The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol. 58:233–247. 1999. View Article : Google Scholar : PubMed/NCBI
32	Latimer CS, Searcy JL, Bridges MT, Brewer LD, Popović J, Blalock EM, Landfield PW, Thibault O and Porter NM: Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice. PLoS One. 6:e268122011. View Article : Google Scholar : PubMed/NCBI
33	Kohman RA, DeYoung EK, Bhattacharya TK, Peterson LN and Rhodes JS: Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice. Brain Behav Immun. 26:803–810. 2012. View Article : Google Scholar : PubMed/NCBI
34	Sung YH, Kim SC, Hong HP, Park CY, Shin MS, Kim CJ, Seo JH, Kim DY, Kim DJ and Cho HJ: Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice. Life Sci. 91:1309–1316. 2012. View Article : Google Scholar : PubMed/NCBI
35	Leem YH, Lee YI, Son HJ and Lee SH: Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23. Biochem Biophys Res Commun. 406:359–365. 2011. View Article : Google Scholar : PubMed/NCBI