Calcium/Calmodulin Kinase II Activity of Hippocampus in Kainate-Induced Epilepsy

Abstract

This study investigated calcium/calmodulin kinase II (CaMKII) activity related to long-standing neuronal injury of the hippocampus in kainate (KA)-induced experimental temporal lobe epilepsy. Epileptic seizure was induced by injection of KA (1 g/ L) dissolved in phosphate buffer (0.1 M, pH 7.4) into the left amygdala. Clinical seizures, histopathologic changes and CaMKII activity of the hippocampus were evaluated. Characteristic early limbic and late seizures were developed. Hippocampal CaMKII activity increased significantly 4 and 8 weeks after intra-amygdaloid injection of KA, when late seizures developed. The histopathologic changes of the hippocampus included swelling of neuronal cytoplasm with nuclear pyknosis and loss of neurons in CA3 during this period. The increased activity of CaMKII may correlate with appearance of distant damage in the hippocampus. The above results indicate that intra-amygdaloid injection of KA produces excitatory signals for ipsilateral CA3 neurons in the hippocampus and that subsequently increased levels of CaMKII in postsynaptic neurons induce neuronal injury via phosphorylation of N-methyl-D-aspartate type glutamate receptor.

Ripple‐related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice

“…The mean duration of all seizures was 65.5 ± 22.5 seconds (Figure C, n = 297 seizures in seven mice). Nissl stains demonstrated profound neuronal loss confined to the ipsilateral amygdala and hippocampal CA3 area, with minimal damage in CA1, similar to prior reports (data not shown).…”

“…To avoid confounds from direct damage to hippocampal cells within the CA1 from chemoconvulsants or seizure‐induced apoptosis, we performed a unilateral injection of kainic acid in the amygdala to generate TLE in mice. In this model of TLE, neuronal cell loss and resultant gliosis occurs in the amygdala and the CA3 subfield of the hippocampus, with relative sparing of the CA1 region . Chronic TLE was verified with video–electroencephalography (EEG) for each mouse, and non‐invasive (ie, without disturbance of the intracellular milieu) juxtacellular electrophysiologic recording techniques were employed in awake control and TLE mice followed by post hoc identification of the recorded dPCs in CA1.…”

“…In this model of TLE, neuronal cell loss and resultant gliosis occurs in the amygdala and the CA3 subfield of the hippocampus, with relative sparing of the CA1 region. [26][27][28][29][30] Chronic TLE was verified with video-electroencephalography (EEG) for each mouse, and non-invasive (ie, without disturbance of the intracellular milieu) juxtacellular electrophysiologic recording techniques 31 were employed in awake control and TLE mice followed by post hoc identification of the recorded dPCs in CA1.…”

Epileptogenesis causes an N-methyl-d-aspartate receptor/Ca2+-dependent decrease in Ca2+/calmodulin-dependent protein kinase II activity in a hippocampal neuronal culture model of spontaneous recurrent epileptiform discharges

“…Alterations in Cam kinase II function have been observed in a number of models of seizure (Blair et al, 1999;Bronstein et al, 1988;Murray et al, 1995;Perlin et al, 1992;Yamagata et al, 2006) and epilepsy (Bronstein et al, 1992;Butler et al, 1995;Churn et al, 2000a;Lee et al, 2001). Both epileptogenesis and the decrease in CaM kinase II activity in the rat pilocarpine model of acquired epilepsy are dependent on NMDA receptor activation during the initial status epilepticus insult (Kochan et al, 2000;Rice and DeLorenzo, 1998) and transgenic modulation of forebrain NMDA receptor structure by inducing expression of the developmental NR2D subunit in mature mouse brain acts to suppress epileptogenesis with electrical kindling (Bengzon et al, 1999).…”

Voltage-Dependent Calcium Channels, Calcium Binding Proteins, and Their Interaction in the Pathological Process of Epilepsy

“…These data may indicate that functional down-regulation of CaMKII could result in the occurrence of epilepsy. However, increased CaMKII in postsynaptic neurons was reported in KA-induced epileptic adult rat brain, [ 135 ]. In the hippocampus of patients with TLE, CaMKII labeling was significantly increased in the granule cell somata and their proximal dendrites [ 136 ].…”