Skip to main content
SpringerLink
Log in

Effect of Exercise Interventions on Kainate Induced Status Epilepticus and Associated Co-morbidities; A Systematic Review and Meta-Analysis

  • Review
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Purpose

To conduct a systematic review and meta-analysis of studies testing the effect of exercise in Kainic-acid (KA) induced status-epilepticus (SE) and to quantify the efficacy of exercise strategies in the prognosis of SE and co-morbidities.

Methods

Two authors searched online databases (Pubmed and Web of Science) independently for studies testing the efficacy of exercise programs in KA-induced SE models. Reviewers autonomously extracted data on models used, exercise interventions and prognosis in all reported outcomes (behavioral, histological, biochemical and cognitive outcomes). All studies were summarized and relevant outcomes’ data were pooled by means of a meta-analysis.

Results

Among 14 selected studies; Quantitative analysis of studies with pre-SE exercise interventions showed significant reduction in mortality rate among 76 animals of four studies (RR = 0.57, [95% CI 0.34, 0.95], p = 0.03, I2 = 57%) and seizure rating score among three studies (n = 56) with MD = − 1.04, [95% CI − 2.07, − 0.00], p = 0.05, I2 = 71%. Three studies (n = 62) presented with improved anti-oxidant enzymes’ profile (SMD = 0.75, [95% CI 0.55, 2.31], p = 0.0008, I2 = 44%) as a result of exercise intervention. Same intervention failed to show any significant measure for BDNF level and neuroprotection assessed through neuronal number in different brain areas with MD = − 1.22, [95% CI − 136.66, 134.22], p = 0.99, I2 = 0% and SMD = − 0.05, [95% CI − 0.62, 0.52], p = 0.86, I2 = 61% respectively. Qualitative review concluded in the reduction of median seizure score, depression and anxiety-like behaviors with improved cognitive performances in pre-SE exercised animals while improved memory and learning capabilities with increased neurogenesis were observed in post-SE exercised models.

Conclusions

Exercise before SE reduces behavioral seizures and oxidative stress with improvements in cognitive abilities. Post-SE exercise enhances learning and memory with neurogenesis in KA models. More extensive research on morphological and biochemical profiles is needed to explore underlying mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

TLE:

Temporal lobe epilepsy

KA:

Kainic acid

SE:

Status epilepticus

SRS:

Spontaneous recurrent seizures

ROC:

Reactive oxygen species

PT:

Physical training

MD:

Mean difference

CI:

Confidence interval

SMD:

Standardized mean difference

RR:

Risk ratios

References

  1. Hu M, Zhu K, Chen XL, Zhang YJ, Zhang JS, Xiao XL, Liu JX, Liu Y (2015) Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus. Exp Neurol 273:273–287. https://doi.org/10.1016/j.expneurol.2015.09.007

    Article  PubMed  Google Scholar 

  2. Hester MS, Danzer SC (2013) Accumulation of abnormal adult-generated hippocampal granule cells predicts seizure frequency and severity. J Neurosci 33(21):8926–8936. https://doi.org/10.1523/jneurosci.5161-12.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vezzani A, Friedman A, Dingledine RJ (2013) The role of inflammation in epileptogenesis. Neuropharmacology 69:16–24. https://doi.org/10.1016/j.neuropharm.2012.04.004

    Article  CAS  PubMed  Google Scholar 

  4. Hellwig S, Gutmann V, Trimble MR, van Elst LT (2013) Cerebellar volume is linked to cognitive function in temporal lobe epilepsy: a quantitative MRI study. Epilepsy Behav 28(2):156–162. https://doi.org/10.1016/j.yebeh.2013.04.020

    Article  PubMed  Google Scholar 

  5. Gorantla VR, Sirigiri A, Volkova YA, Millis RM (2016) Effects of swimming exercise on limbic and motor cortex neurogenesis in the kainate-lesion model of temporal lobe epilepsy. Cardiovasc Psychiatry Neurol 2016:3915767. https://doi.org/10.1155/2016/3915767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Levesque M, Avoli M, Bernard C (2016) Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration. J Neurosci Methods 260:45–52. https://doi.org/10.1016/j.jneumeth.2015.03.009

    Article  PubMed  Google Scholar 

  7. Kim HJ, Song W, Kim JS, Jin EH, Kwon MS, Park S (2014) Synergic effect of exercise and lipoic acid on protection against kainic acid induced seizure activity and oxidative stress in mice. Neurochem Res 39(8):1579–1584. https://doi.org/10.1007/s11064-014-1350-y

    Article  CAS  PubMed  Google Scholar 

  8. Ben-Ari Y (1985) Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14(2):375–403

    Article  CAS  Google Scholar 

  9. Levesque M, Avoli M (2013) The kainic acid model of temporal lobe epilepsy. Neurosci Biobehav Rev 37(10 Pt 2):2887–2899. https://doi.org/10.1016/j.neubiorev.2013.10.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arida RM, de Almeida AC, Cavalheiro EA, Scorza FA (2013) Experimental and clinical findings from physical exercise as complementary therapy for epilepsy. Epilepsy Behav 26(3):273–278. https://doi.org/10.1016/j.yebeh.2012.07.025

    Article  PubMed  Google Scholar 

  11. Iqbal M, Rahman MS, Zafar S, Chen XL, Liu JX, Liu Y (2017) Systematic review and meta-analysis of the efficacy of different exercise programs in pilocarpine induced status epilepticus models. Epilepsy Behav 73:256–267. https://doi.org/10.1016/j.yebeh.2017.06.007

    Article  PubMed  Google Scholar 

  12. Esquivel E, Chaussain M, Plouin P, Ponsot G, Arthuis M (1991) Physical exercise and voluntary hyperventilation in childhood absence epilepsy. Electroencephalogr Clin Neurophysiol 79(2):127–132

    Article  CAS  Google Scholar 

  13. Capovilla G, Kaufman KR, Perucca E, Moshe SL, Arida RM (2016) Epilepsy, seizures, physical exercise, and sports: a report from the ILAE Task Force on sports and epilepsy. Epilepsia 57(1):6–12. https://doi.org/10.1111/epi.13261

    Article  PubMed  Google Scholar 

  14. Nakken KO, Loyning A, Loyning T, Gloersen G, Larsson PG (1997) Does physical exercise influence the occurrence of epileptiform EEG discharges in children? Epilepsia 38(3):279–284

    Article  CAS  Google Scholar 

  15. Nakken KO (1999) Physical exercise in outpatients with epilepsy. Epilepsia 40(5):643–651

    Article  CAS  Google Scholar 

  16. Allendorfer JB, Arida RM (2018) Role of physical activity and exercise in alleviating cognitive impairment in people With epilepsy. Clin Ther 40(1):26–34. https://doi.org/10.1016/j.clinthera.2017.12.004

    Article  PubMed  Google Scholar 

  17. Roth DL, Goode KT, Williams VL, Faught E (1994) Physical exercise, stressful life experience, and depression in adults with epilepsy. Epilepsia 35(6):1248–1255

    Article  CAS  Google Scholar 

  18. Koirala GR, Lee D, Eom S, Kim NY, Kim HD (2017) Altered brain functional connectivity induced by physical exercise may improve neuropsychological functions in patients with benign epilepsy. Epilepsy Behav 76:126–132. https://doi.org/10.1016/j.yebeh.2017.06.021

    Article  PubMed  Google Scholar 

  19. Eom S, Lee MK, Park JH, Jeon JY, Kang HC, Lee JS, Kim HD (2014) The impact of an exercise therapy on psychosocial health of children with benign epilepsy: a pilot study. Epilepsy Behav 37:151–156. https://doi.org/10.1016/j.yebeh.2014.06.017

    Article  PubMed  Google Scholar 

  20. Tchekalarova J, Shishmanova M, Atanasova D, Stefanova M, Alova L, Lazarov N, Georgieva K (2015) Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats. Brain Res 1625:39–53. https://doi.org/10.1016/j.brainres.2015.08.022

    Article  CAS  PubMed  Google Scholar 

  21. Kim HJ, Song W, Jin EH, Kim J, Chun Y, An EN, Park S (2016) Combined low-intensity exercise and ascorbic acid attenuates kainic acid-induced seizure and oxidative stress in mice. Neurochem Res 41(5):1035–1041. https://doi.org/10.1007/s11064-015-1789-5

    Article  CAS  PubMed  Google Scholar 

  22. Holmes PV, Reiss JI, Murray PS, Dishman RK, Spradley JM (2015) Chronic exercise dampens hippocampal glutamate overflow induced by kainic acid in rats. Behav Brain Res 284:19–23. https://doi.org/10.1016/j.bbr.2015.02.002

    Article  CAS  PubMed  Google Scholar 

  23. Kim HJ, Kim IK, Song W, Lee J, Park S (2013) The synergic effect of regular exercise and resveratrol on kainate-induced oxidative stress and seizure activity in mice. Neurochem Res 38(1):117–122. https://doi.org/10.1007/s11064-012-0897-8

    Article  CAS  PubMed  Google Scholar 

  24. Reiss JI, Dishman RK, Boyd HE, Robinson JK, Holmes PV (2009) Chronic activity wheel running reduces the severity of kainic acid-induced seizures in the rat: possible role of galanin. Brain Res 1266:54–63. https://doi.org/10.1016/j.brainres.2009.02.030

    Article  CAS  PubMed  Google Scholar 

  25. Gobbo OL, O’Mara SM (2005) Combining exercise and cyclooxygenase-2 inhibition does not ameliorate learning deficits after brain insult, despite an increase in BDNF levels. Brain Res 1046(1–2):224–229. https://doi.org/10.1016/j.brainres.2005.03.046

    Article  CAS  PubMed  Google Scholar 

  26. Georgieva KN, Hadjieva MS, Shishmanova-Doseva MS, Terzieva DD, Georgiev NG, Andreev GG, Tchekalarova JD (2017) Effect of training at lactate threshold intensity on maximal time to exhaustion, depression and anxiety behaviour of spontaneously hypertensive rats after kainate-induced status epilepticus. Folia Med 59(1):91–97. https://doi.org/10.1515/folmed-2017-0004

    Article  CAS  Google Scholar 

  27. Gobbo OL, O’Mara SM (2005) Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived neurotrophic factor. Behav Brain Res 159(1):21–26. https://doi.org/10.1016/j.bbr.2004.09.021

    Article  CAS  PubMed  Google Scholar 

  28. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1. https://doi.org/10.1186/2046-4053-4-1

    Article  PubMed  PubMed Central  Google Scholar 

  29. Caspersen CJ, Powell KE, Christenson GM (1985) Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 100(2):126–131

    CAS  PubMed  PubMed Central  Google Scholar 

  30. de Almeida AA, Gomes da Silva S, Lopim GM, Vannucci Campos D, Fernandes J, Cabral FR, Arida RM (2017) Resistance exercise reduces seizure occurrence, attenuates memory deficits and restores BDNF signaling in rats with chronic epilepsy. Neurochem Res 42(4):1230–1239. https://doi.org/10.1007/s11064-016-2165-9

    Article  CAS  Google Scholar 

  31. Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1(2):97–111. https://doi.org/10.1002/jrsm.12

    Article  PubMed  Google Scholar 

  32. Lau J, Ioannidis JPA, Terrin N, Schmid CH, Olkin I (2006) The case of the misleading funnel plot. BMJ 333(7568):597–600. https://doi.org/10.1136/bmj.333.7568.597

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14:43. https://doi.org/10.1186/1471-2288-14-43

    Article  PubMed  PubMed Central  Google Scholar 

  34. Macleod MR, O’Collins T, Howells DW, Donnan GA (2004) Pooling of animal experimental data reveals influence of study design and publication bias. Stroke 35(5):1203–1208. https://doi.org/10.1161/01.str.0000125719.25853.20

    Article  PubMed  Google Scholar 

  35. Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, Niu Y, Du L (2015) The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid-Based Med 8(1):2–10. https://doi.org/10.1111/jebm.12141

    Article  PubMed  Google Scholar 

  36. Ramsden M, Berchtold NC, Patrick Kesslak J, Cotman CW, Pike CJ (2003) Exercise increases the vulnerability of rat hippocampal neurons to kainate lesion. Brain Res 971(2):239–244

    Article  CAS  Google Scholar 

  37. Gorantla VR, Pemminati S, Bond V, Meyers DG, Millis RM (2016) Effects of swimming exercise on learning and memory in the kainate-lesion model of temporal lobe epilepsy. J Clin Diagn Res 10(11):Cf01–Ccf05. https://doi.org/10.7860/jcdr/2016/22100.8835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen L, Gong S, Shan LD, Xu WP, Zhang YJ, Guo SY, Hisamitsu T, Yin QZ, Jiang XH (2006) Effects of exercise on neurogenesis in the dentate gyrus and ability of learning and memory after hippocampus lesion in adult rats. Neurosci Bull 22(1):1–6

    PubMed  Google Scholar 

  39. Gomes FG, Gomes Da Silva S, Cavalheiro EA, Arida RM (2014) Beneficial influence of physical exercise following status epilepticus in the immature brain of rats. Neuroscience 274:69–81. https://doi.org/10.1016/j.neuroscience.2014.05.024

    Article  CAS  PubMed  Google Scholar 

  40. Binder DK, Croll SD, Gall CM, Scharfman HE (2001) BDNF and epilepsy: too much of a good thing? Trends Neurosci 24(1):47–53

    Article  CAS  Google Scholar 

  41. Simonato M, Tongiorgi E, Kokaia M (2006) Angels and demons: neurotrophic factors and epilepsy. Trends Pharmacol Sci 27(12):631–638. https://doi.org/10.1016/j.tips.2006.10.002

    Article  CAS  Google Scholar 

  42. Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JS, Yoneda Y, Kim HC (2011) Role of oxidative stress in epileptic seizures. Neurochem Int 59(2):122–137. https://doi.org/10.1016/j.neuint.2011.03.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Freitas RM (2009) Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine. Neurosci Lett 462(3):225–229. https://doi.org/10.1016/j.neulet.2009.07.037

    Article  CAS  PubMed  Google Scholar 

  44. Liu J, Wang A, Li L, Huang Y, Xue P, Hao A (2010) Oxidative stress mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus. Seizure 19(3):165–172. https://doi.org/10.1016/j.seizure.2010.01.010

    Article  CAS  PubMed  Google Scholar 

  45. Blomstrand E, Perrett D, Parry-Billings M, Newsholme EA (1989) Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytryptamine metabolism in six different brain regions in the rat. Acta Physiol Scand 136(3):473–481. https://doi.org/10.1111/j.1748-1716.1989.tb08689.x

    Article  CAS  PubMed  Google Scholar 

  46. Weise J, Engelhorn T, Dorfler A, Aker S, Bahr M, Hufnagel A (2005) Expression time course and spatial distribution of activated caspase-3 after experimental status epilepticus: contribution of delayed neuronal cell death to seizure-induced neuronal injury. Neurobiol Dis 18(3):582–590. https://doi.org/10.1016/j.nbd.2004.10.025

    Article  CAS  PubMed  Google Scholar 

  47. Kim BS, Kim MY, Leem YH (2011) Hippocampal neuronal death induced by kainic acid and restraint stress is suppressed by exercise. Neuroscience 194:291–301. https://doi.org/10.1016/j.neuroscience.2011.06.029

    Article  CAS  PubMed  Google Scholar 

  48. Roy H, Lippe S, Lussier F, Sauerwein HC, Lortie A, Lacroix J, Lassonde M (2011) Developmental outcome after a single episode of status epilepticus. Epilepsy Behav 21(4):430–436. https://doi.org/10.1016/j.yebeh.2011.05.009

    Article  PubMed  Google Scholar 

  49. Hotting K, Roder B (2013) Beneficial effects of physical exercise on neuroplasticity and cognition. Neurosci Biobehav Rev 37(9):2243–2257. https://doi.org/10.1016/j.neubiorev.2013.04.005

    Article  PubMed  Google Scholar 

  50. Balu DT, Lucki I (2009) Adult hippocampal neurogenesis: regulation, functional implications, and contribution to disease pathology. Neurosci Biobehav Rev 33(3):232–252. https://doi.org/10.1016/j.neubiorev.2008.08.007

    Article  PubMed  Google Scholar 

  51. Liu JX, Hu M, Zhu K, Chen XL, Zhang JS, Yuan B, Liu Y (2016) Residual neurogenesis in chronically epileptic hippocampus of mice. Epilepsy Res 127:40–49. https://doi.org/10.1016/j.eplepsyres.2016.08.019

    Article  PubMed  Google Scholar 

  52. Hattiangady B, Rao MS, Shetty AK (2004) Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus. Neurobiol Dis 17(3):473–490. https://doi.org/10.1016/j.nbd.2004.08.008

    Article  CAS  PubMed  Google Scholar 

  53. Amado D, Cavalheiro EA, Bentivoglio M (1993) Epilepsy and hormonal regulation: the patterns of GnRH and galanin immunoreactivity in the hypothalamus of epileptic female rats. Epilepsy Res 14(2):149–159

    Article  CAS  Google Scholar 

  54. Amado D, Cavalheiro EA (1998) Hormonal and gestational parameters in female rats submitted to the pilocarpine model of epilepsy. Epilepsy Res 32(1–2):266–274

    Article  CAS  Google Scholar 

  55. Backstrom T, Zetterlund B, Blom S, Romano M (1984) Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy. Acta Neurol Scand 69(4):240–248

    Article  CAS  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Institute of Neurobiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, 76 West Yanta Road, Xi’an city, 710061, China

    Muneeb Iqbal, Jian-Xin Liu & Yong Liu

  2. Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, 76 West Yanta Road, Xi’an city, 710061, China

    Shakir Ullah

  3. University Institute of Physical Therapy, University of Lahore, 1 km Defence road, Lahore, Pakistan

    Salman Zafar

  4. College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, 710062, China

    Tanzeela Nisar

Authors
  1. Muneeb Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shakir Ullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Salman Zafar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tanzeela Nisar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Xin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong Liu.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Iqbal, M., Ullah, S., Zafar, S. et al. Effect of Exercise Interventions on Kainate Induced Status Epilepticus and Associated Co-morbidities; A Systematic Review and Meta-Analysis. Neurochem Res 44, 1005–1019 (2019). https://doi.org/10.1007/s11064-019-02758-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-019-02758-9

Keywords

Search

Navigation