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(Abst. 1.177), 2018

Detailed Spectral Profile Analysis of Penicillin G-Induced Epileptiform Discharges During Freezing in Anesthetized Rats
Authors: Tatsuji Tokiwa, Hiroshima City University; Lev Zimin, Waseda University; Takao Inoue, Yamaguchi University Graduate School of Medicine; Sadahiro Nomura, Yamaguchi University Graduate School of Medicine; Michiyasu Suzuki, Yamaguchi University Graduate School of Medicine; and Takeshi Yamakawa, Fuzzy Logic Systems Institute
Content: Rationale: Cryosurgery is an alternative technique for minimally invasive treatment of lesions. We have recently proposed the palm-sized cryoprobe system and examined cryosurgery for epilepsy in a Wistar rat brain model. And it was confirmed that penicillin G (PG)-induced epileptiform discharges (EDs) mostly vanished after freezing. However, EDs have provoked again after insufficient freezing. Inadequate freezing is not visually detectable during and just after freezing and is not predictable beforehand. To manage this problem, we examined whether intraoperative monitoring of electrocorticograms (ECoGs) can predict recurrence of EDs after cryosurgery. Methods: The palm-sized cryoprobe system was applied to focal seizures in a Wistar rat model in which EDs were induced in advance by intracerebral injection of PG (n = 12; weight, 377 ± 56 g). During stable induction of EDs, the cryoprobe tip which is 0.7 mm in diameter was carefully inserted into the epileptic region and this region was immediately frozen for approximately 20 min. R-410a was used as a refrigerant (boiling points of –51.4 °C at atmospheric pressure). After the series of pre-freezing, freezing, and post-freezing, rats in which PG-induced EDs relapsed within 3?h were defined as the ED-relapsed (EDR) group (n = 5), and other rats were defined as the ED-vanished (EDV) group (n = 7). Time-frequency analysis was conducted on the ECoGs in each group through each freezing series. For comparison between individuals, differences between the two groups with recorded ECoGs in the freezing period and between the three distinct periods in each group were analyzed by Mann-Whitney U test and a paired t-test with Bonferroni correction, respectively. Results: In the EDV group, the frequency power was significantly decreased in all bands in the freezing and post-freezing periods, compared to the pre-freezing period, and especially for the delta band (P < 0.01). Relapse of PG-induced EDs on ECoG after the freezing series was associated with the remaining power of the delta band (P < 0.05) in the freezing period more strongly in the EDR group than in the EDV group. Conclusions: Success or failure of the freezing procedure can be predicted by the specificity of the delta band of the ECoG obtained intraoperatively. We believe that these experimental results will contribute to an establishment of reliable cryotherapy as an alternative and novel surgical treatment for intractable epilepsy. Funding: This work was supported by a Grant-in-Aid for Specially Promoted Research (Project No. 20001008) and a Grant-in-Aid for Young Scientists (B) (Project Number 17K13019) from MEXT of Japan, and Hiroshima City University Grant for Special Academic Research (General Study)