The Role of the Perirhinal Cortex for Secondary Generalization in Kainic Acid–Induced Seizures
Authors: Fukumoto Shin‐ichirou , Tanaka Shigeya , Akaike Kouichi , Toujou Hideshi , Imamura Shinichi , Uetsuhara Kouichi , Takigawa Morikuni 
Published: August 2009

Purpose: We previously reported that a lesion in the perirhinal cortex (PRC) made by the microinjection of ibotenic acid resulted in the suppression of secondary generalization in kainic acid (KA‐induced limbic status epilepticus (LSE) in rats (Epilepsia 1996;37:95–6). We again studied the effects of PRC lesions made by electrocoagulation on KA‐induced LSE and also examined the differences in glucose metabolism between the PRC‐lesioned and the control rats by using the [14C]2‐deoxyglucose method. Methods: Fourteen male Wistar rats, weighing 250–300 g, were used for this study: eight for the behavioral and electroencephalographic (EEG) study, and six for the metabolic study. Under pentobarbital (PTB) anesthesia, the electrocoagulation probe was stereotaxically inserted into the PRC and the lesion (80°C, 1 m 30 s) was made. For EEG recordings, bipolar twisted electrodes were placed into the left sensorimotor cortex (LCx), the left hasolateral nucleus of the amygdala (LA), and the left dorsal hippocampus (LH). A cannula was implanted obliquely into the LA for KA injection. In the control group, an electrocoagulation probe was inserted into the PRC, but the lesion was not made. After a 7‐day recovery period, 1 μg of KA (0.5 μ1) was injected into the LA. All rats were observed for clinical and EEG changes for 6 h and were perfused under deep PTB anesthesia for the histopathologic examination (n = 8). We also studied the glucose metabolism in rats with a PRC lesion and the controls (n = 6). The rats were anesthetized with 1.5% halothane, and the femoral vein was cannulated. After recovery from the anesthesia, KA was injected into the LA. One and half hours after the KA injection, when all rats were exhibiting LSE, a bolus of [14C]2‐deoxyglucose (100 μCi/kg) was injected intravenously. Thirty minutes later, the rats were decapitated, the brains carefully removed and frozen in liquid freon‐12 (‐40°C). Consecutive coronal sections 20 pm thick were prepared in a cryostat, mounted on glass coverslips and dried at 60°C. Autoradiograms were made by exposing a Kodak SB5 film to the dried sections in a roentogenogram cassette for 7 days. The pattern of the local cerebral glucose utilization (LCGU) was compared between the rats with a PRC lesion and the controls. Results: In rats with a PRC lesion, the seizures were less frequent and severe compared with the controls. Interestingly, electrographic propagation of the epileptic discharges to the LCx was suppressed during the observation period. Clinically, motor manifestations were less frequently observed. In the histopathologic examination, hippocampal neuronal damage, especially in the CA3 and CA4 fields, was present in the control rats: however, only slight neuronal damage was seen in the hippocampus in the PRC‐lesioned rats. In the glucose metabolic study, a decrease in LCGU was confined to the LCx compared with the controls. Conclusions: In the PRC kindling model, McIntyre et al. demonstrated that the PRC has strong excitability, and the latency to onset of convulsive seizures is very short. Furthermore, Holmes et al. reported that the NMDA receptors located in the PRC play a major role in the modulation of after discharge activity elicited from the endopiriform nucleus or prepiriform cortex. Our study also suggests that the PRC is one of the important pathways for the secondary generalization of the seizure discharges from the limbic system to the sensorimotor cortex.