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Review
, 14 Suppl 1 (Suppl 1), 65-73

Hippocampal Neurogenesis and Neural Stem Cells in Temporal Lobe Epilepsy

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Review

Hippocampal Neurogenesis and Neural Stem Cells in Temporal Lobe Epilepsy

Ramkumar Kuruba et al. Epilepsy Behav.

Abstract

Virtually all mammals, including humans, exhibit neurogenesis throughout life in the hippocampus, a learning and memory center in the brain. Numerous studies in animal models imply that hippocampal neurogenesis is important for functions such as learning, memory, and mood. Interestingly, hippocampal neurogenesis is very sensitive to physiological and pathological stimuli. Certain pathological stimuli such as seizures alter both the amount and the pattern of neurogenesis, though the overall effect depends on the type of seizures. Acute seizures are classically associated with augmentation of neurogenesis and migration of newly born neurons into ectopic regions such as the hilus and the molecular layer of the dentate gyrus. Additional studies suggest that abnormally migrated newly born neurons play a role in the occurrence of epileptogenic hippocampal circuitry characteristically seen after acute seizures, status epilepticus, or head injury. Recurrent spontaneous seizures such as those typically observed in chronic temporal lobe epilepsy are associated with substantially reduced neurogenesis, which, interestingly, coexists with learning and memory impairments and depression. In this review, we discuss both the extent and the potential implications of abnormal hippocampal neurogenesis induced by acute seizures as well as recurrent spontaneous seizures. We also discuss the consequences of chronic spontaneous seizures on differentiation of neural stem cell progeny in the hippocampus and strategies that are potentially useful for normalizing neurogenesis in chronic temporal lobe epilepsy.

Figures

Figure 1
Figure 1
Schematic of different changes that occur following acute seizures. Acute seizures or status epilepticus typically occur following head trauma, stroke, brain injury or brain infections. Acute seizures induce multiple structural alterations in the brain particularly the hippocampus. The major hippocampal changes include degeneration of fractions of dentate hilar neurons and CA1-CA3 pyramidal neurons, aberrant sprouting of mossy fibers into the dentate supragranular layer and substantial loss of inhibitory interneurons. Acute seizures also transiently up-regulate multiple neurotrophic factors and other proteins in the hippocampus. These include nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), neuropeptide Y (NPY), sonic hedgehog (Shh) and Cystatin C. Additional cellular changes in the hippocampus following acute seizures comprise increased neurogenesis, abnormal migration of newly born neurons into the dentate hilus and dentate molecular layer, and occurrence of hilar basal dendrites in newly added granule cells. All of the above changes are believed to contribute to the formation of aberrant circuitry and epileptogenesis in the hippocampus, and learning and memory impairments.
Figure 2
Figure 2
Schematic showing various time-points after acute seizures at which interventional strategies may be applied to alleviate the acute seizure induced chronic epilepsy, learning and memory impairments, and depression. Acute seizures induce multiple structural, neurochemical and cellular changes in the hippocampus, which are believed to contribute to the development of chronic epilepsy characterized by spontaneous seizures. Chronic epilepsy leads to a substantial decline in hippocampal neurogenesis which is believed to contribute towards learning and memory impairments and depression. Interventional strategies such as administration of neurotrophic factors, antidepressant therapy, physical exercise, exposure to enriched environment, and grafting of neural stem cells (NSCs) and glial progenitors, may be useful when applied during the latent period (or silent phase after acute seizures), at the commencement of spontaneous seizures or after the establishment of chronic epilepsy. Interventional strategies such as antiepileptic drug therapy are likely useful at all of the above time-time points as well as immediately after the onset of acute seizures.

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