100 rats were randomly divided into a sham-operated group and middle cerebral artery occlusion (MCAO) modeling groups. The sham group after surgery was observed for 14 days. After MCAO, some rats received isometric contraction training (ICT) which was as follows: an atraumatic tourniquet was placed around left or right hind limb to achieve hind limb ischemia for 5 min, followed by 5 min of reperfusion, 4 cycles for one time, once a day, and five days per week. The MCAO modeling groups included the following four groups: i) a group only received MCAO, and was observed for seven days (MCAO-7d), ii) a group only received MCAO, and was observed for 14 days (MCAO-14d), iii) a group, after MCAO, received ICT for seven days (ICT-7d), and iv) a group, after MCAO, received ICT for 14 days (ICT-14d). Brain infarct area, behavioral outcomes, the number of neurons, apoptosis, cerebral edema and cerebral water content were assessed, respectively. The mRNA expression of vascular endothelial growth factor (VEGF) was assayed with RT-PCR, and protein expression of VEGF was quantified with western blot. compared with MCAO controls, cerebral infarction, neurological deficits and neuronal apoptosis were reduced significantly in the ICT groups, while the number of neurons was increased. Moreover, the mRNA expression of VEGF and protein expression of VEGF were enhanced after 1 and 2 weeks of ICT. ICT may promote angiogenesis and neuroprotection after ischemic stroke and this new remodeling method provide a novel strategy for rehabilitation of stroke patients.

Pukou Branch of Jiangsu People's Hospital Nanjing City Jiangsu Province P R China

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Orellana-Urzúa S, Rojas I, Líbano L, Rodrigo R. Pathophysiology of ischemic stroke: Role of oxidative stress. Curr Pharm Des. 2020;26:4246–4260. doi: 10.2174/1381612826666200708133912. PubMed DOI

Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123:e18–e209. doi: 10.1161/CIR.0b013e3182009701. PubMed DOI PMC

Hankey GJ. Secondary stroke prevention. Lancet Neurol. 2014;13:178–194. doi: 10.1016/S1474-4422(13)70255-2. PubMed DOI

Kuriakose D, Xiao Z. Pathophysiology and treatment of stroke: Present status and future perspectives. Int J Mol Sci. 2020;21:7609. doi: 10.3390/ijms21207609. PubMed DOI PMC

Choi WJ, Li Y, Wang RK. Monitoring acute stroke progression: Multi-parametric OCT imaging of cortical perfusion, flow, and tissue scattering in a mouse model of permanent focal ischemia. IEEE Trans Med Imaging. 2019;38:1427–1437. doi: 10.1109/TMI.2019.2895779. PubMed DOI PMC

Yu Q, Li X, Li Y, Fu J, Xiao Z. Effects of combined electroacupuncture and exercise training on motor function and microtubule-associated protein 2 expression in the middle and late stages of cerebral infarction in rats. Acupunct Med. 2020;38:175–180. doi: 10.1177/0964528419882937. PubMed DOI

Saunders DH, Sanderson M, Hayes S, Johnson L, Kramer S, Carter DD, Jarvis H, Brazzelli M, Mead GE. Physical fitness training for stroke patients. Cochrane Database Syst Rev. 2020;3:CD003316. doi: 10.1002/14651858.CD003316.pub7. PubMed DOI PMC

Prior PL, Suskin N. Exercise for stroke prevention. Stroke Vasc Neurol. 2018;3:59–68. doi: 10.1136/svn-2018-000155. PubMed DOI PMC

Svoboda J, Litvinec A, Kala D, Pošusta A, Vávrová L, Jiruška P, Otáhal J. Strain differences in intraluminal thread model of middle cerebral artery occlusion in rats. Physiol Res. 2019;68:37–48. doi: 10.33549/physiolres.933958. PubMed DOI

Wu J, Mamas M, Rashid M, Weston C, Hains J, Luescher T, de Belder MA, Deanfield JE, Gale CP. Patient response, treatments, and mortality for acute myocardial infarction during the COVID-19 pandemic. Eur Heart J Qual Care Clin Outcomes. 2021;7:238–246. doi: 10.1093/ehjqcco/qcaa062. PubMed DOI PMC

Wang WW, Chen DZ, Zhao M, Yang XF, Gong DR. Prior transient ischemic attacks may have a neuroprotective effect in patients with ischemic stroke. Arch Med Sci. 2017;13:1057–1061. doi: 10.5114/aoms.2016.63744. PubMed DOI PMC

Li S, Hafeez A, Noorulla F, Geng X, Shao G, Ren C, Lu G, Zhao H, Ding Y, Ji X. Preconditioning in neuroprotection: From hypoxia to ischemia. Prog Neurobiol. 2017;157:79–91. doi: 10.1016/j.pneurobio.2017.01.001. PubMed DOI PMC

Kim DH, Lee JH, Yu SM, An CM. The effects of ankle position on torque and muscle activity of the knee extensor during maximal isometric contraction. J Sport Rehabil. 2020;29:37–42. doi: 10.1123/jsr.2018-0145. PubMed DOI

Kozlowski B, Pageaux B, Hubbard EF, St Peters B, Millar PJ, Power GA. Perception of effort during an isometric contraction is influenced by prior muscle lengthening or shortening. Eur J Appl Physiol. 2021;121:2531–2542. doi: 10.1007/s00421-021-04728-y. PubMed DOI

Lin S, Chen Y, Li Y, Li J, Lu X. Physical ischaemia induced by isometric exercise facilitated collateral development in the remote ischaemic myocardium of humans. Clin Sci (Lond) 2014;127:581–588. doi: 10.1042/CS20130618. PubMed DOI

Zhang X, Zheng Y, Geng C, Guan J, Wang L, Zhang X, Cheng Y, Li J, Lu X. Isometric exercise promotes arteriogenesis in rats after myocardial infarction. J Biomed Res. 2021;35:436–447. doi: 10.7555/JBR.35.20210062. PubMed DOI PMC

Saunders E, Clark BC, Clark LA, Grooms DR. Development of a trunk motor paradigm for use in neuroimaging. Transl Neurosci. 2020;11:193–200. doi: 10.1515/tnsci-2020-0116. PubMed DOI PMC

Lin S, Lu X, Chen S, Ye F, Zhang J, Ma Y, Li J. Human coronary collateral recruitment is facilitated by isometric exercise during acute coronary occlusion. J Rehabil Med. 2012;44:691–695. doi: 10.2340/16501977-0989. PubMed DOI

Moreira JBN, Wohlwend M, Wisl⊘ff U. Exercise and cardiac health: physiological and molecular insights. Nat Metab. 2020;2:829–839. doi: 10.1038/s42255-020-0262-1. PubMed DOI

Stock JM, Chouramanis NV, Chirinos JA, Edwards DG. Dynamic and isometric handgrip exercise increases wave reflection in healthy young adults. J Appl Physiol (1985) 2020;129:709–717. doi: 10.1152/japplphysiol.00281.2020. PubMed DOI PMC

Gao M, Lu X, Chen W, Xiao GH, Zhang Y, Yu R, Li J. Randomized clinical trial of physiological ischemic training for patients with coronary heart disease complicated with heart failure: Safety of training, VEGF of peripheral blood and quality of life. Exp Ther Med. 2018;16:260–264. doi: 10.3892/etm.2018.6175. PubMed DOI PMC

Ni J, Lu H, Lu X, Jiang M, Peng Q, Ren C, Xiang J, Mei C, Li J. The evolving concept of physiological ischemia training vs. ischemia preconditioning. J Biomed Res. 2015;29:445–450. doi: 10.7555/jbr.29.20140142. PubMed DOI PMC

Wan C, Li J, Yang C, Hu D, Bi S. Dynamics of endogenous endothelial progenitor cells homing modulated by physiological ischaemia training. J Rehabil Med. 2015;47:87–93. doi: 10.2340/16501977-1891. PubMed DOI

Zheng Y, Xiao M, Li L, Li J, Reinhardt JD, Lu X. Remote physiological ischemic training promotes coronary angiogenesis via molecular and cellular mobilization after myocardial ischemia. Cardiovasc Ther. 2017;35:e12257. doi: 10.1111/1755-5922.12257. PubMed DOI

Zheng Y, Lu X, Li J, Zhang Q, Reinhardt JD. Impact of remote physiological ischemic training on vascular endothelial growth factor, endothelial progenitor cells and coronary angiogenesis after myocardial ischemia. Int J Cardiol. 2014;177:894–901. doi: 10.1016/j.ijcard.2014.10.034. PubMed DOI

Hahn CD, Manlhiot C, Schmidt MR, Nielsen TT, Redington AN. Remote ischemic per-conditioning: a novel therapy for acute stroke? Stroke. 2011;42:2960–2962. doi: 10.1161/STROKEAHA.111.622340. PubMed DOI

Zhen X, Zheng Y, Hong X, Chen Y, Gu P, Tang J, Cheng H, Yuan TF, Lu X. Physiological ischemic training promotes brain collateral formation and improves functions in patients with acute cerebral infarction. Front Neurol. 2016;7:235. doi: 10.3389/fneur.2016.00235. PubMed DOI PMC

Ruan GX, Kazlauskas A. Axl is essential for VEGF-A-dependent activation of PI3K/Akt. EMBO J. 2012;31:1692–1703. doi: 10.1038/emboj.2012.21. PubMed DOI PMC

Chen X, Zheng Q, Li W, Lu Y, Ni Y, Ma L, Fu Y. SOX5 induces lung adenocarcinoma angiogenesis by inducing the expression of VEGF through STAT3 signaling. Onco Targets Ther. 2018;11:5733–5741. doi: 10.2147/OTT.S176533. PubMed DOI PMC

Hou Y, Wang K, Wan W, Cheng Y, Pu X, Ye X. Resveratrol provides neuroprotection by regulating the JAK2/STAT3/PI3K/AKT/mTOR pathway after stroke in rats. Genes Dis. 2018;5:245–255. doi: 10.1016/j.gendis.2018.06.001. PubMed DOI PMC

Samakova A, Gazova A, Sabova N, Valaskova S, Jurikova M, Kyselovic J. The PI3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia. Physiol Res. 2019;68(Suppl 2):S131–S138. doi: 10.33549/physiolres.934345. PubMed DOI

Wang N, Yang L, Zhang H, Lu X, Wang J, Cao Y, Chen L, Wang X, Cong L, Li J, Wang N, Liu Z, Wang L. MicroRNA-9a-5p alleviates ischemia injury after focal cerebral ischemia of the rat by targeting ATG5-mediated autophagy. Cell Physiol Biochem. 2018;45:78–87. doi: 10.1159/000486224. PubMed DOI

Lopez MS, Vemuganti R. Modeling transient focal ischemic stroke in rodents by intraluminal filament method of middle cerebral artery occlusion. Methods Mol Biol. 2018;1717:101–113. doi: 10.1007/978-1-4939-7526-6_9. PubMed DOI

Lin A, Li J, Zhao Y, Xiao M, Xiao B, Lu X, Wan C. Effect of physiologic ischemic training on protection of myocardial infarction in rabbits. Am J Phys Med Rehabil. 2011;90:97–105. doi: 10.1097/PHM.0b013e3182017483. PubMed DOI

Hong Y, Liu Q, Peng M, Bai M, Li J, Sun R, Guo H, Xu P, Xie Y, Li Y, Liu L, Du J, Liu X, Yang B, Xu G. High-frequency repetitive transcranial magnetic stimulation improves functional recovery by inhibiting neurotoxic polarization of astrocytes in ischemic rats. J Neuroinflammation. 2020;17:150. doi: 10.1186/s12974-020-01747-y. PubMed DOI PMC

Kulkarni P, Bhosle MR, Lu SF, Simon NS, Iriah S, Brownstein MJ, Ferris CF. Evidence of early vasogenic edema following minor head impact that can be reduced with a vasopressin V1a receptor antagonist. Brain Res Bull. 2020;165:218–227. doi: 10.1016/j.brainresbull.2020.10.001. PubMed DOI PMC

Borshchev YY, Minasian SM, Burovenko IY, Borshchev VY, Protsak ES, Semenova NY, Borshcheva OV, Galagudza MM. Effects of tetracycline on myocardial infarct size in obese rats with chemically-induced colitis. PLoS One. 2019;14:e0225185. doi: 10.1371/journal.pone.0225185. PubMed DOI PMC

Sharma R, Iovine C, Agarwal A, Henkel R. TUNEL assay-standardized method for testing sperm DNA fragmentation. Andrologia. 2021;53:e13738. doi: 10.1111/and.13738. PubMed DOI

Xiao M, Lu X, Li J, Li L, Li Y. Physiologic ischaemic training induces endothelial progenitor cell mobilization and myocardial angiogenesis via endothelial nitric oxide synthase related pathway in rabbits. J Cardiovasc Med (Hagerstown) 2014;15:280–287. doi: 10.2459/JCM.0b013e32836009fe. PubMed DOI

B⊘tker HE, Kharbanda R, Schmidt MR, B⊘ttcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010;375:727–734. doi: 10.1016/S0140-6736(09)62001-8. PubMed DOI

Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol. 2006;47:2277–2282. doi: 10.1016/j.jacc.2006.01.066. PubMed DOI

Li L, Luo W, Huang L, Zhang W, Gao Y, Jiang H, Zhang C, Long L, Chen S. Remote perconditioning reduces myocardial injury in adult valve replacement: a randomized controlled trial. J Surg Res. 2010;164:e21–e26. doi: 10.1016/j.jss.2010.06.016. PubMed DOI

Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H, Heusch G. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol. 2010;105:657–664. doi: 10.1007/s00395-010-0104-5. PubMed DOI

Varnavas VC, Kontaras K, Glava C, Maniotis CD, Koutouzis M, Baltogiannis GG, Papalois A, Kolettis TM, Kyriakides ZS. Chronic skeletal muscle ischemia preserves coronary flow in the ischemic rat heart. Am J Physiol Heart Circ Physiol. 2011;301:H1229–H1235. doi: 10.1152/ajpheart.00232.2011. PubMed DOI

Nyquist P, Georgakis MK. Remote ischemic preconditioning effects on brain vasculature. Neurology. 2019;93:15–16. doi: 10.1212/WNL.0000000000007724. PubMed DOI

Shen M, Gao J, Li J, Su J. Effect of ischaemic exercise training of a normal limb on angiogenesis of a pathological ischaemic limb in rabbits. Clin Sci (Lond) 2009;117:201–208. doi: 10.1042/CS20080212. PubMed DOI

Wang Y, Liu Y, Sun K, Wei Y, Fu L, Hou Z, Yi X, Ma D, Wang W, Jin X. The differential neuroprotection of HSP70-hom gene single nucleotide polymorphisms: In vitro (neuronal hypoxic injury model) and in vivo (rat MCAO model) studies. Gene. 2019;710:354–362. doi: 10.1016/j.gene.2019.05.059. PubMed DOI

Li J, Tao T, Xu J, Liu Z, Zou Z, Jin M. HIF-1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia-reperfusion injury in a rat MCAO model. Int J Mol Med. 2020;45:1027–1036. doi: 10.3892/ijmm.2020.4480. PubMed DOI PMC

Ren L, Wei C, Li K, Lu Z. LncRNA MALAT1 up-regulates VEGF-A and ANGPT2 to promote angiogenesis in brain microvascular endothelial cells against oxygen-glucose deprivation via targetting miR-145. Biosci Rep. 2019;39 doi: 10.1042/bsr20180226. doi: 10.1042/BSR20180226. PubMed DOI PMC

Lange C, Storkebaum E, de Almodóvar CR, Dewerchin M, Carmeliet P. Vascular endothelial growth factor: a neurovascular target in neurological diseases. Nat Rev Neurol. 2016;12:439–454. doi: 10.1038/nrneurol.2016.88. PubMed DOI

Silverman DA, Martinez VK, Dougherty PM, Myers JN, Calin GA, Amit M. Cancer-associated neurogenesis and nerve-cancer cross-talk. Cancer Res. 2021;81:1431–1440. doi: 10.1158/0008-5472.CAN-20-2793. PubMed DOI PMC

Chen L, Lin G, Chen K, Wan F, Liang R, Sun Y, Chen X, Zhu X. VEGF knockdown enhances radiosensitivity of nasopharyngeal carcinoma by inhibiting autophagy through the activation of mTOR pathway. Sci Rep. 2020;10:16328. doi: 10.1038/s41598-020-73310-x. PubMed DOI PMC

Shang J, Gao ZY, Zhang LY, Wang CY. Over-expression of JAZF1 promotes cardiac microvascular endothelial cell proliferation and angiogenesis via activation of the Akt signaling pathway in rats with myocardial ischemia-reperfusion. Cell Cycle. 2019;18:1619–1634. doi: 10.1080/15384101.2019.1629774. PubMed DOI PMC