Is exposure to enriched environment beneficial for functional post-lesional recovery in temporal lobe epilepsy?

Abstract

Exposure to environmental enrichment has been shown to induce robust neuronal plasticity in both intact and injured adult central nervous system, including up-regulation of multiple neurotrophic factors, enhanced neurogenesis in the dentate gyrus of the hippocampus, and improved spatial learning and memory function. Neuronal plasticity, though mostly adaptive and abnormal, also occurs during certain neurodegenerative conditions such as the temporal lobe epilepsy (TLE). The TLE is characterized by hippocampal neurodegeneration, aberrant mossy fiber sprouting, spontaneous recurrent motor seizures, cognitive deficits, and abnormally enhanced neurogenesis during the early phase and dramatically declined neurogenesis during the chronic phase of the disease. As enrichment has been found to be beneficial for treating animal models of Alzheimer's, Parkinson's, and Huntington's diseases, there is considerable interest in determining the efficacy of this strategy for preventing or treating chronic TLE after the initial precipitating brain injury. This review first discusses the proof of principle behind the potential application of the environmental enrichment strategy for preventing or treating TLE after brain injury. The subsequent chapters confer the portrayed beneficial effects of enrichment for functional post-lesional recovery in TLE and the possible complications which may arise from housing epilepsy-prone or epileptic rats in enriched environmental conditions. The final segment discusses studies that are essential for further understanding the efficacy of this approach for preventing or treating TLE.

Enriched Environment Altered Aberrant Hippocampal Neurogenesis and Improved Long-Term Consequences After Temporal Lobe Epilepsy in Adult Rats

“…These toys and positions were changed 1-2 times/week to bestow environmental novelty. The enrichment also comprised increased social interaction, as larger numbers of animals (about 10 rats in our experiment) were usually housed together in bigger and wider cages with exploratory chambers (Dhanushkodi and Shetty 2008;Fares et al 2013).…”

“…9 A summary figure explaining the possible molecular mechanisms and pathways of EE treatment on chronic TLE. Status epilepticus results in multiple pathological changes including hippocampal neurons loss, aberrant sprouting of mossy fibers, and spontaneous recurrent seizures, which eventually lead to declined DG neurogenesis and cognitive impairment in chronic TLE (Dhanushkodi and Shetty 2008). It should be noted that the role of aberrant mossy fibers sprouting in epileptogenesis remains controversial (Scharfman et al 2003;Sloviter et al 2006;Buckmaster 2014).…”

Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice

“…Nevertheless, in our study, we observed a complete preservation of hippocampal cytoarchitecture and functional recovery when HEK-CM was injected 72 h after KA-induced hippocampal injury. The discrepancy may be caused by prolonged BBB opening after KA injection, owing to its seizure-inducing potential [1,17]. Thus, to utilize the beneficial effects of cell-based therapy for various neurodegenerative diseases, it is important to understand the pattern and duration of BBB disruption for a given neurodegenerative condition that would help us to identify an appropriate therapeutic window for intervention.…”

“…Hippocampal neurodegeneration is one of the hallmarks in neurological and neurodegenerative diseases such as temporal lobe epilepsy and Alzheimer disease [1,2]. Excitotoxicity caused by augmented release of glutamate plays a significant role in neuronal losses in these disease conditions.…”

Compensatory Neurogenesis in the Injured Adult Brain

“…Supporting this, a range of studies have demonstrated that administration of neurotrophic factors to both the normal and injured adult rodent brain can enhance hippocampal neurogenesis (Lichtenwalner, et al, 2001, Yoshimura, et al, 2001, Scharfman, et al, 2005, Rai, et al, 2007, Paradiso, et al, 2009, Paradiso, et al, 2011. Performing physical exercise and environmental enrichment have also been shown to enhance hippocampal neurogenesis, potentially through increased expression of a range of mitogenic factors such as BDNF, FGF2, NGF, IGF-1 and VEGF as well as phosphorylation of cAMP-response binding protein (CREB) (Nithianantharajah, et al, 2006, Van Praag, 2008, Llorens-Martín, et al, 2009, Lafenetre, et al, 2011 and may provide an appealing noninvasive therapeutic approach for the treatment of chronic TLE (Dhanushkodi, et al, 2008, Arida, et al, 2009. Antidepressant therapy in chronic TLE is another interesting approach for increasing neurogenesis and reducing cognitive impairments, as antidepressant therapy enhances hippocampal neurogenesis probably via increases in levels of serotonin, noradrenaline, BDNF, CREB and a range of other mitogenic factors (Sahay, et al, 2007, Thomas, et al, 2008, Lanni, et al, 2009.…”