Loss of Hippocampal Neurons after Kainate Treatment Correlates with Behavioral Deficits

Abstract

Treating rats with kainic acid induces status epilepticus (SE) and leads to the development of behavioral deficits and spontaneous recurrent seizures later in life. However, in a subset of rats, kainic acid treatment does not induce overt behaviorally obvious acute SE. The goal of this study was to compare the neuroanatomical and behavioral changes induced by kainate in rats that developed convulsive SE to those who did not. Adult male Wistar rats were treated with kainic acid and tested behaviorally 5 months later. Rats that had experienced convulsive SE showed impaired performance on the spatial water maze and passive avoidance tasks, and on the context and tone retention tests following fear conditioning. In addition, they exhibited less anxiety-like behaviors than controls on the open-field and elevated plus-maze tests. Histologically, convulsive SE was associated with marked neuron loss in the hippocampal CA3 and CA1 fields, and in the dentate hilus. Rats that had not experienced convulsive SE after kainate treatment showed less severe, but significant impairments on the spatial water maze and passive avoidance tasks. These rats had fewer neurons than control rats in the dentate hilus, but not in the hippocampal CA3 and CA1 fields. Correlational analyses revealed significant relationships between spatial memory indices of rats and neuronal numbers in the dentate hilus and CA3 pyramidal field. These results show that a part of the animals that do not display intense behavioral seizures (convulsive SE) immediately after an epileptogenic treatment, later in life, they may still have noticeable structural and functional changes in the brain.

The Effect of Curcumin on Anxiety and Recognition Memory in Kainate Model of Epileptic Rats

“…However, in the kainate model of epilepsy, epileptic rats were previously reported to have decreased anxiety-like behaviours compared to controls [33,34] . These behavioural alterations could be a reflection of disinhibited hyperactive behaviour, which might be related to the collateral brain lesions in ventral hippocampus, entorhinal and amygdala (i.e.…”

“…These behavioural alterations could be a reflection of disinhibited hyperactive behaviour, which might be related to the collateral brain lesions in ventral hippocampus, entorhinal and amygdala (i.e. fear expression networks) [33,34] . Damage on these networks potentially cause an inaccurate interpretation on threatening situations and thus, causing a reduction in anxiety or enhance the impulsive inadapted behaviour [33] .…”

“…fear expression networks) [33,34] . Damage on these networks potentially cause an inaccurate interpretation on threatening situations and thus, causing a reduction in anxiety or enhance the impulsive inadapted behaviour [33] . The discrepancy of current result could be related to the time for behavioural testing.…”

“…Studies showed that epileptic rats spent a prolonged period, approximately 5 mo to reach a maximal seizure frequency, i.e., plateau phase after seizure induction [35] . Therefore, studies on epilepsy at time point less than 5 mo may generally reveal less severe behavioural deficits due to less frequent spontaneous seizures and less neuropathological changes involved [33] . In this study, the behavioural testing was performed approximately one week post SE, hence, the result was parallel to studies on epileptic animal at time point of one to three months post SE [3,32] .…”

Human pluripotent stem cells ameliorate NMDA-induced hippocampal degeneration and related functional deficits

“…Using this approach, the CA3 region has been shown to be the area of the hippocampus involved in the consolidation of short-term memory into long-term memory, and spatial navigation (Kesner, 2007). While lesioning of the CA3 with a low dose of excitotoxins can show the link to memory formation, lesioning with high doses can lead to seizures and CA3 neurodegeneration (Maia et al, 2014).…”