Region‐specific plasticity in the epileptic rat brain: A hippocampal and extrahippocampal analysis

Abstract

SUMMARYPurpose: Recent evidence suggests that aberrant neuro/gliogenesis and/or inflammation play critical roles in epileptogenesis. Although the plastic and inflammatory changes have been described in the postseizure hippocampus, little data is available concerning extrahippocampal regions, notably in the piriform and entorhinal cortices, amygdala, and parts of the thalamus. In this study, we examined histological changes in whole epileptic rat brain, with respect to cell death, cell genesis, and inflammation. Methods and Results: Experimental status epilepticus (SE) was induced using a lithium-pilocarpine injection. Neuronal death was evident in the amygdala, piriform, and entorhinal cortices, as well as the subfields of hippocampus. Microglial activation was observed in more extended limbic areas, such as, the hippocampus, entorhinal, perirhinal and piriform cortices, amygdala, thalamus, and hypothalamus, and a robust increase of cell genesis was noted in these damaged areas. The majority of newly generated cells in extrahippocampal areas proliferated in situ, and differentiated mainly into astrocytes or oligodendrocytes. In addition, stromal cell-derived factor-1a was found to be induced in close temporal and anatomical association with seizure-induced plasticity. Discussion: These findings indicate that neuronal death, inflammation, and cell genesis are substantially associated throughout the entire brain and that they may influence the epileptogenic process and clinical manifestations.

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

“…Since increased GABA release in the DG during the early post-seizure period was thought to regulate the proliferation and survival of newborn neurons, SDF-1 may promote the proliferation of newborn neurons through augmentation of the GABAergic inputs during the seizures. The SDF-1 protein level has been shown to be significantly increased as early as 24 h after SE, and this elevation can last for 1 month (Jung et al 2009). Similarly, in the present study, we found the expression of SDF-1 and CXCR4 recovered at the baseline levels on 42 days after KA injection by western blot analysis, while EE for 30 days could delay the attenuation of the expression of SDF-1 and CXCR4.…”

“…The dead or injured neurons, reactive glial cells, and endothelial cells have been reported to release SDF-1 after brain injury such as stroke or seizures (Schonemeier et al 2008;Jung et al 2009). SDF-1/CXCR4 plays a particularly important role in adult neurogenesis and synergistically influences the GABAergic synaptic inputs to DG neural progenitors then modulates the neurogenesis of the DG directly (Bhattacharyya et al 2008).…”

“…SDF-1/CXCR4 plays a particularly important role in adult neurogenesis by means of regulating the proliferation of neural progenitor cells, mediating the migration, differentiation, and functional integration of newly born neurons into existing neuronal networks (Cheng and Qin 2012;Cui et al 2013;Marquez-Curtis and JanowskaWieczorek 2013). Studies have shown that the levels of SDF-1 protein are increased after status epilepticus (SE) and that the increase in SDF-1 in the hippocampus is relevant to cell genesis (Jung et al 2009). Therefore, it is reasonable that the SDF-1/CXCR4 pathway may be involved in the altered microenvironments of newly born neurons after seizures.…”

Theta Rhythmopathy as a Cause of Cognitive Disability in TLE

“…Silencing of the same population of GABAergic medial septal neurons in nonepileptic animals greatly diminishes theta oscillations (22). There is also a loss of neurons in the entorhinal cortex (40,61), with detailed studies showing loss of dorsal layer III medial entorhinal cortex neurons that form the temporoammonic input to the lacunosum moleculare layer in epileptic animals (40) and human TLE (62). This loss, when combined with the expansion of the perforant path, may mediate some of the alterations of theta power and coherence in the hippocampus (40), as well as changes to theta phaseprecession (58).…”

CXCR4 Antagonist AMD3100 Suppresses the Long-Term Abnormal Structural Changes of Newborn Neurons in the Intraventricular Kainic Acid Model of Epilepsy

“…SDF-1/ CXCR4 plays particularly important roles in adult neurogenesis through mediating the proliferation of neuroprogenitor cells, regulating the migration, differentiation, and functional integration of newborn neurons into existing neuronal networks [11][12][13]. There was evidence showing that SDF-1 protein levels were increased after status epilepticus (SE) in the hippocampus, which was associated with cell genesis [14]. Therefore, SDF-1/CXCR4 pathway may be involved in the altered microenvironments of newborn neurons after seizures.…”