Document Type : Original Article
Authors
1 Department of Sport Sciences, Faculty of Education and Psychology, University of Sistan and Baluchestan, Zahedan, Iran
2 Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
3 Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
Abstract
Background: Traumatic brain injury (TBI) remains a primary cause of mortality and is a significant contributor to various impairments, including somatosensory and cognitive deficits. The prevention and management of injuries require regular daily exercise. In this research, we examined the impact of eight weeks of aerobic exercise on neurological outcomes, brain water content (BWC), blood-brain barrier (BBB) permeability, electrophysiological characteristics, and concentrations of brain-derived neurotrophic factor (BDNF) in an experimental model of TBI.
Methods: Sixty-four male Wistar rats were divided into four groups: Control, Training, TBI, and Training-TBI. TBI was induced using the Marmarou method. After TBI induction, eight weeks of aerobic exercise were performed using a five-line animal treadmill. Then, the rats’ memory and learning were assessed using the Morris water maze. Electrodes were implanted in the skulls of anesthetized rats for single-unit recording. Neurological scores, BWC, BBB permeability, and cerebral tissue BDNF concentrations were measured 48 hours after exercise. Statistical analysis was conducted using one-way ANOVA, followed by Tukey’s post hoc test for multiple comparisons. P values < 0.05 were considered statistically significant.
Results: Aerobic exercise significantly reversed the decrement of neurological scores, the neuronal firing rate of the hippocampus, increments of BWC, cognition deficits, and cerebral tissue Evans blue concentration after TBI compared with control. It also increased cerebral tissue BDNF, which had significantly decreased in TBI.
Conclusion: Our results suggest that through BDNF increment, aerobic exercise exerts neuroprotective effects on memory impairment and the decrement of neuronal firing rate caused by TBI.
Keywords
Main Subjects
- Lefevre-Dognin C, Cogné M, Perdrieau V, Granger A, Heslot C, Azouvi P. Definition and epidemiology of mild traumatic brain injury. Neurochirurgie. 2021;67(3):218-21. doi: 10.1016/j.neuchi.2020.02.002.
- Sharma S, Ifergan I, Kurz JE, Linsenmeier RA, Xu D, Cooper JG, et al. Intravenous immunomodulatory nanoparticle treatment for traumatic brain injury. Ann Neurol. 2020;87(3):442-55. doi: 10.1002/ana.25675.
- Loosemore M, Knowles CH, Whyte GP. Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies. BMJ. 2007;335(7624):809. doi: 10.1136/bmj.39342.690220.55.
- Hellal F, Bonnefont-Rousselot D, Croci N, Palmier B, Plotkine M, Marchand-Verrecchia C. Pattern of cerebral edema and hemorrhage in a mice model of diffuse brain injury. Neurosci Lett. 2004;357(1):21-4. doi: 10.1016/j.neulet.2003.12.036.
- Julien J, Joubert S, Ferland MC, Frenette LC, Boudreau- Duhaime MM, Malo-Véronneau L, et al. Association of traumatic brain injury and Alzheimer disease onset: a systematic review. Ann Phys Rehabil Med. 2017;60(5):347- 56. doi: 10.1016/j.rehab.2017.03.009.
- Shively S, Scher AI, Perl DP, Diaz-Arrastia R. Dementia resulting from traumatic brain injury: what is the pathology? Arch Neurol. 2012;69(10):1245-51. doi: 10.1001/ archneurol.2011.3747.
- Massey JS, Meares S, Batchelor J, Bryant RA. An exploratory study of the association of acute posttraumatic stress, depression, and pain to cognitive functioning in mild traumatic brain injury. Neuropsychology. 2015;29(4):530-42. doi: 10.1037/neu0000192.
- Jha RM, Kochanek PM, Simard JM. Pathophysiology and treatment of cerebral edema in traumatic brain injury. Neuropharmacology. 2019;145(Pt B):230-46. doi: 10.1016/j. neuropharm.2018.08.004.
- Cherian I, Beltran M, Landi A, Alafaci C, Torregrossa F, Grasso G. Introducing the concept of “CSF‐shift edema” in traumatic brain injury. J Neurosci Res. 2018;96(4):744-52. doi: 10.1002/ jnr.24145.
- Kozler P, Maresova D, Pokorny J. Cytotoxic brain edema induced by water intoxication and vasogenic brain edema induced by osmotic BBB disruption lead to distinct pattern of ICP elevation during telemetric monitoring in freely moving rats. Neuro Endocrinol Lett. 2019;40(6):249-56.
- Huang YN, Yang LY, Greig NH, Wang YC, Lai CC, Wang JY. Neuroprotective effects of pifithrin-α against traumatic brain injury in the striatum through suppression of neuroinflammation, oxidative stress, autophagy, and apoptosis. Sci Rep. 2018;8(1):2368. doi: 10.1038/s41598- 018-19654-x.
- Besnier F, Labrunée M, Pathak A, Pavy-Le Traon A, Galès C, Sénard JM, et al. Exercise training-induced modification in autonomic nervous system: an update for cardiac patients. Ann Phys Rehabil Med. 2017;60(1):27-35. doi: 10.1016/j. rehab.2016.07.002.
- Weinstein AA, Chin LMK, Collins J, Goel D, Keyser RE, Chan L. Effect of aerobic exercise training on mood in people with traumatic brain injury: a pilot study. J Head Trauma Rehabil. 2017;32(3):E49-56. doi: 10.1097/htr.0000000000000253.
- Briken S, Rosenkranz SC, Keminer O, Patra S, Ketels G, Heesen C, et al. Effects of exercise on Irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis. J Neuroimmunol. 2016;299:53-8. doi: 10.1016/j. jneuroim.2016.08.007.
- Okamoto M, Mizuuchi D, Omura K, Lee M, Oharazawa A, Yook JS, et al. High-intensity intermittent training enhances spatial memory and hippocampal neurogenesis associated with BDNF signaling in rats. Cereb Cortex. 2021;31(9):4386- 97. doi: 10.1093/cercor/bhab093.
- Amaral SL, Papanek PE, Greene AS. Angiotensin II and VEGF are involved in angiogenesis induced by short-term exercise training. Am J Physiol Heart Circ Physiol. 2001;281(3):H1163- 9. doi: 10.1152/ajpheart.2001.281.3.H1163.
- Nokia MS, Lensu S, Ahtiainen JP, Johansson PP, Koch LG, Britton SL, et al. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. J Physiol. 2016;594(7):1855-73. doi: 10.1113/jp271552.
- Chin LM, Keyser RE, Dsurney J, Chan L. Improved cognitive performance following aerobic exercise training in people with traumatic brain injury. Arch Phys Med Rehabil. 2015;96(4):754-9. doi: 10.1016/j.apmr.2014.11.009.
- Cetinkaya C, Sisman AR, Kiray M, Camsari UM, Gencoglu C, Baykara B, et al. Positive effects of aerobic exercise on learning and memory functioning, which correlate with hippocampal IGF-1 increase in adolescent rats. Neurosci Lett. 2013;549:177-81. doi: 10.1016/j.neulet.2013.06.012.
- Bao TH, Miao W, Han JH, Yin M, Yan Y, Wang WW, et al. Spontaneous running wheel improves cognitive functions of mouse associated with miRNA expressional alteration in hippocampus following traumatic brain injury. J Mol Neurosci. 2014;54(4):622-9. doi: 10.1007/s12031-014-0344-1.
- Soltani N, Soltani Z, Khaksari M, Ebrahimi G, Hajmohammmadi M, Iranpour M. The changes of brain edema and neurological outcome, and the probable mechanisms in diffuse traumatic brain injury induced in rats with the history of exercise. Cell Mol Neurobiol. 2020;40(4):555-67. doi: 10.1007/s10571- 019-00753-w.
- Mirshekar MA, Shahraki M, Najafi R, Shabani S. The ameliorative effects of myricetin on neurobehavioral activity, electrophysiology, and biochemical changes in an animal model of traumatic brain injury. Learn Motiv. 2019;68:101597. doi: 10.1016/j.lmot.2019.101597.
- Mirshekar MA, Sarkaki A, Farbood Y, Gharib Naseri MK, Badavi M, Mansouri MT, et al. Neuroprotective effects of gallic acid in a rat model of traumatic brain injury: behavioral, electrophysiological, and molecular studies. Iran J Basic Med Sci. 2018;21(10):1056-63. doi: 10.22038/ ijbms.2018.29639.7165.
- Horii N, Hasegawa N, Fujie S, Uchida M, Iemitsu K, Inoue K, et al. Effect of combination of chlorella intake and aerobic exercise training on glycemic control in type 2 diabetic rats. Nutrition. 2019;63-64:45-50. doi: 10.1016/j.nut.2019.01.008.
- Li W, Park H, Guo E, Jo W, Sim KM, Lee SK. Aerobic exercise training inhibits neointimal formation via reduction of PCSK9 and LOX-1 in atherosclerosis. Biomedicines. 2020;8(4):92. doi: 10.3390/biomedicines8040092.
- Hosseini R, Mirshekar MA, Sedaghat G, Clark CC, Jalali M. The effect of sub-chronic administration of brewed coffee on long-term potentiation in a rat model of Alzheimer’s disease. Shiraz E Med J. 2022;23(7):e113268. doi: 10.5812/semj- 113268.
- Arabmoazzen S, Mirshekar MA. Evaluation of the effects of metformin as adenosine monophosphate-activated protein kinase activator on spatial learning and memory in a rat model of multiple sclerosis disease. Biomed Pharmacother. 2021;141:111932. doi: 10.1016/j.biopha.2021.111932.
- Dubal DB, Wise PM. Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology. 2001;142(1):43-8. doi: 10.1210/endo.142.1.7911.
- Holmin S, Höjeberg B. In situ detection of intracerebral cytokine expression after human brain contusion. Neurosci Lett. 2004;369(2):108-14. doi: 10.1016/j.neulet.2004.07.044.
- Taupin V, Toulmond S, Serrano A, Benavides J, Zavala F. Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion. Influence of pre- and post-traumatic treatment with Ro5 4864, a peripheral-type (p site) benzodiazepine ligand. J Neuroimmunol. 1993;42(2):177-85. doi: 10.1016/0165-5728(93)90008-m.
- Silva LF, Hoffmann MS, da Rosa Gerbatin R, da Silva Fiorin F, Dobrachinski F, Mota BC, et al. Treadmill exercise protects against pentylenetetrazol-induced seizures and oxidative stress after traumatic brain injury. J Neurotrauma. 2013;30(14):1278-87. doi: 10.1089/neu.2012.2577.
- Mota BC, Pereira L, Souza MA, Silva LF, Magni DV, Ferreira AP, et al. Exercise pre-conditioning reduces brain inflammation and protects against toxicity induced by traumatic brain injury: behavioral and neurochemical approach. Neurotox Res. 2012;21(2):175-84. doi: 10.1007/s12640-011-9257-8.
- Neese SL, Sherill LK, Tan AA, Roosevelt RW, Browning RA, Smith DC, et al. Vagus nerve stimulation may protect GABAergic neurons following traumatic brain injury in rats: an immunocytochemical study. Brain Res. 2007;1128(1):157- 63. doi: 10.1016/j.brainres.2006.09.073.
- Keefe KM, Sheikh IS, Smith GM. Targeting neurotrophins to specific populations of neurons: NGF, BDNF, and NT-3 and their relevance for treatment of spinal cord injury. Int J Mol Sci. 2017;18(3):548. doi: 10.3390/ijms18030548.
- hic factor in neuronal plasticity and neuroregeneration: new pharmacological concepts for old and new drugs. Neural Regen Res. 2018;13(6):983-4. doi: 10.4103/1673- 5374.233438.
- Zhong Y, Zhu Y, He T, Li W, Li Q, Miao Y. Brain-derived neurotrophic factor inhibits hyperglycemia-induced apoptosis and downregulation of synaptic plasticity-related proteins in hippocampal neurons via the PI3K/Akt pathway. Int J Mol Med. 2019;43(1):294-304. doi: 10.3892/ijmm.2018.3933.
- Spriggs MJ, Thompson CS, Moreau D, McNair NA, Wu CC, Lamb YN, et al. Human sensory long-term potentiation (LTP) predicts visual memory performance and is modulated by the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. bioRxiv [Preprint]. March 18, 2018. Available from: https://www.biorxiv.org/content/10.1101/284315v1.
- Feldmann LK, Le Prieult F, Felzen V, Thal SC, Engelhard K, Behl C, et al. Proteasome and autophagy-mediated impairment of late long-term potentiation (l-LTP) after traumatic brain injury in the somatosensory cortex of mice. Int J Mol Sci. 2019;20(12):3048. doi: 10.3390/ijms20123048.
- Liu W, Li L, Kuang H, Xia Y, Wang Z, Liu S, et al. Proteomic profile of carbonylated proteins screen regulation of apoptosis via CaMK signaling in response to regular aerobic exercise. Biomed Res Int. 2018;2018:2828143. doi: 10.1155/2018/2828143.