Environmental Enrichment Reduces Cortical Excitability In Rats Submitted To Status Epilepticus In The Pilocarpine Model: An Evaluation From Cortical Spreading Depression

Roberto Carlos da Silva Bandeira1, Luís Gustavo Carvalho dos Santos2, Christian Barker Silva Santisteban2, Angela Amancio-dos-Santos3

1Federal University of Pernambuco – UFPE, Health Sciences Center, Department of Pharmaceutical Sciences, Recife – PE, Brazil; 2Federal University of Pernambuco – UFPE, Medical Sciences Center, Recife – PE, Brazil; 3Federal University of Pernambuco – UFPE, Biosciences Center, Department of Physiology and Pharmacology, Recife – PE, Brazil

Objective: This study verified if the exposure to environmental enrichment (EE) influences brain excitability, evaluated by cortical spreading depression (CSD), in rats submitted to status epilepticus (SE).

Methods: At 35 days of age, male Wistar rats were divided into two experimental groups: pilocarpine (PILO), which received a single dose of pilocarpine hydrochloride to induce SE, and saline (SAL), which were the group control. On the following day, half of the animals in each group were exposed to EE; while the other half was kept in the standard environment (S), considered control. At 67 days of age, the rats were anesthetized and submitted to CSD.

Results: Pilocarpine, isolated, reduced the speed of propagation and increased the duration and amplitude of CSD. EE, itself, reduced the speed of propagation and duration, but increased the amplitude of CSD. In the animals exposed to EE that undergone SE, the values of CSD parameters became closer to the control group.

Conclusion: Our results indicate that EE reduced the cortical excitability induced by SE, possibly by promoting antioxidant effects at the brain level, inducing neurogenesis and/or improving the excitatory/inhibitory balance of neurotransmitters.

Keywords: epilepsy. cortical spreading depression. pilocarpine.

Free Full-text PDF

How to cite this article:
Roberto Carlos da Silva Bandeira, Luís Gustavo Carvalho dos Santos, Christian Barker Silva Santisteban, Angela Amancio-dos-Santos. Environmental Enrichment Reduces Cortical Excitability In Rats Submitted To Status Epilepticus In The Pilocarpine Model: An Evaluation From Cortical Spreading Depression. International Journal of Neuroscience Research, 2021; 5:13. DOI: 10.28933/ijnr-2021-07-2005


1. Nithianantharajah J, Hannan A. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nature Reviews Neuroscience. 2006;7(9):697-709.
2. Mármol F, Sánchez J, Torres M, Chamizo V. Environmental enrichment in the absence of wheel running produces beneficial behavioural and anti-oxidative effects in rats. Behavioural Processes. 2017;144:66-71.
3. Ohline S, Abraham W. Environmental enrichment effects on synaptic and cellular physiology of hippocampal neurons. Neuropharmacology. 2019;145:3-12.
4. Alves D, Sousa M, Tavares M, Santos L, Batista-de-Oliveira-Hornsby M, Amancio-dos-Santos A. Environmental enrichment reduces brain excitability in adult rats overnourished during lactation. Arquivos de Neuro-Psiquiatria. 2019;77(8):555-559.
5. Fernandes M. Epilepsia do lobo temporal: mecanismos e perspectivas. Estudos Avançados. 2013;27(77):85-98.
6. Scorza F, Arida R, Naffah-Mazzacoratti M, Scerni D, Calderazzo L, Cavalheiro E. The pilocarpine model of epilepsy: what have we learned?. Anais da Academia Brasileira de Ciências. 2009;81(3):345-365.
7. Kinjo, E. R. Conexinas na epilepsia experimental induzida por pilocarpina: abordagem molecular e eletrofisiológica [tese]. São Paulo: Instituto de Ciências Biomédicas; 2011.
8. Somjen G. Aristides Leão’s discovery of cortical spreading depression. Journal of Neurophysiology. 2005;94(1):2-4.
9. Gryglas A, Smigiel R. Migraine and Stroke: What’s the Link? What to Do?. Current Neurology and Neuroscience Reports. 2017;17(3).
10. Vrinda M, Sasidharan A, Aparna S, Srikumar B, Kutty B, Shankaranarayana Rao B. Enriched environment attenuates behavioral seizures and depression in chronic temporal lobe epilepsy. Epilepsia. 2017;58(7):1148-1158.
11. Sampedro-Piquero P, Zancada-Menendez C, Begega A, Rubio S, Arias J. Effects of environmental enrichment on anxiety responses, spatial memory and cytochrome c oxidase activity in adult rats. Brain Research Bulletin. 2013;98:1-9.
12. Guedes R, Cavalheiro E. Blockade of spreading depression in chronic epileptic rats: reversion by diazepam. Epilepsy Research. 1997;27(1):33-40.
13. Santos L. G. C. e Amancio-dos-Santos A. O efeito nootrópico sobre a depressão alastrante cortical: um possível mecanismo de ação antiepiléptica. Recife: Relatório (Iniciação Científica), Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, 2019.
14. Leo L, Gherardini L, Barone V, De Fusco M, Pietrobon D, Pizzorusso T et al. Increased Susceptibility to Cortical Spreading Depression in the Mouse Model of Familial Hemiplegic Migraine Type 2. PLoS Genetics. 2011;7(6):e1002129.
15. Vitor-de-Lima S, Medeiros L, Benevides R, dos Santos C, Lima da Silva N, Guedes R. Monosodium glutamate and treadmill exercise: Anxiety-like behavior and spreading depression features in young adult rats. Nutritional Neuroscience. 2017;22(6):435-443.
16. Nogueira R, Pessoa D, da Silva E, Costa E. Can a hypercholesterolemic diet change the basal brain electrical activity and during status epilepticus in rats?. Metabolic Brain Disease. 2018;34(1):71-77.
17. Pestana R, Kinjo E, Hernandes M, Britto L. Reactive oxygen species generated by NADPH oxidase are involved in neurodegeneration in the pilocarpine model of temporal lobe epilepsy. Neuroscience Letters. 2010;484(3):187-191.
18. Auvergne R, Leré C, El Bahh B, Arthaud S, Lespinet V, Rougier A et al. Delayed kindling epileptogenesis and increased neurogenesis in adult rats housed in an enriched environment. Brain Research. 2002;954(2):277-285.
19. Herring A, Blome M, Ambrée O, Sachser N, Paulus W, Keyvani K. Reduction of cerebral oxidative stress following environmental enrichment in mice with Alzheimer-like pathology. Brain Pathol. 2020;20(1):166-175.
20. Muhammad M, Magaji R, Mohammed A, Isa A, Magaji M. Effect of resveratrol and environmental enrichment on biomarkers of oxidative stress in young healthy mice. Metabolic Brain Disease. 2016;32(1):163-170.
21. Monteiro H, Barreto-Silva N, Santos G, Santos A, Sousa M, Amâncio-dos-Santos Â. Physical exercise versus fluoxetine: Antagonistic effects on cortical spreading depression in Wistar rats. European Journal of Pharmacology. 2015;762:49-54.
22. Jacotte-Simancas A, Costa-Miserachs D, Coll-Andreu M, Torras-Garcia M, Borlongan C, Portell-Cortés I. Effects of Voluntary Physical Exercise, Citicoline, and Combined Treatment on Object Recognition Memory, Neurogenesis, and Neuroprotection after Traumatic Brain Injury in Rats. Journal of Neurotrauma. 2015;32(10):739-751.
23. Sonn J, Mayevsky A. Responses to Cortical Spreading Depression under Oxygen Deficiency. The Open Neurology Journal. 2012;6(1):6-17.

Terms of Use/Privacy Policy/ Disclaimer/ Other Policies:
You agree that by using our site, you have read, understood, and agreed to be bound by all of our terms of use/privacy policy/ disclaimer/ other policies (click here for details)

CC BY 4.0
This work and its PDF file(s) are licensed under a Creative Commons Attribution 4.0 International License.