Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado.
Department of Neurosurgery, University at Buffalo Jacob's School of Medicine and Biomedical Sciences, Buffalo, New York.
J Neurophysiol. 2021 Jun 1;125(6):2166-2177. doi: 10.1152/jn.00098.2021. Epub 2021 May 5.
Unilateral-onset spike-wave discharges (SWDs) following fluid percussion injury (FPI) in rats have been used for nearly two decades as a model for complex partial seizures in human posttraumatic epilepsy (PTE). This study determined if SWDs with a unilateral versus bilateral cortical onset differed. In this experiment, 2-mo-old rats received severe FPI (3 atm) or sham surgery and were instrumented for chronic video-electrocorticography (ECoG) recording (up to 9 mo). The antiseizure drug, carbamazepine (CBZ), and the antiabsence drug, ethosuximide (ETX), were administered separately to determine if they selectively suppressed unilateral- versus bilateral-onset SWDs, respectively. SWDs did not significantly differ between FPI and sham rats on any measured parameter (wave-shape, frequency spectrum, duration, or age-related progression), including unilateral (∼17%) versus bilateral (∼83%) onsets. SWDs with a unilateral onset preferentially originated ipsilateral to the craniotomy in both FPI and sham rats, suggesting that the unilateral-onset SWDs were related to surgical injury and not specifically to FPI. ETX profoundly suppressed SWDs with either unilateral or bilateral onsets, and CBZ had no effect on either type of SWD. These results suggest that SWDs with either a unilateral or bilateral onset have a pharmacosensitivity similar to absence seizures and are very different from the complex partial seizures of PTE. Therefore, SWDs with a unilateral onset after FPI are not a model of the complex partial seizures that occur in PTE, and their use for finding new treatments for PTE could be counterproductive, particularly if their close similarity to normal brain oscillations is not acknowledged. Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial seizures in human posttraumatic epilepsy (PTE), compared to bilateral-onset SWDs thought to reflect human absence seizures. Here, we show that both unilateral- and bilateral-onset SWDs following traumatic brain injury are suppressed by the antiabsence drug ethosuximide and are unaffected by the antiseizure drug carbamazepine. We propose that unilateral-onset SWDs are not useful for studying mechanisms of, or treatments for, PTE.
单侧起始的尖波放电（SWD）在大鼠颅脑损伤后（FPI）已被用于研究人类创伤后癫痫（PTE）中的复杂部分性发作近二十年。本研究旨在确定皮质单侧起始与双侧起始的 SWD 是否存在差异。在本实验中，2 月龄大鼠接受严重的 FPI（3 atm）或假手术，并进行慢性视频脑电图（ECoG）记录（最长 9 个月）。给予抗癫痫药物卡马西平（CBZ）和抗失神药物乙琥胺（ETX），以确定它们是否分别选择性地抑制单侧起始与双侧起始的 SWD。FPI 和假手术大鼠的 SWD 在任何测量参数（波形、频谱、持续时间或年龄相关进展）上均无显著差异，包括单侧（约 17%）与双侧（约 83%）起始。FPI 和假手术大鼠中，皮质单侧起始的 SWD 优先起源于开颅术同侧，提示单侧起始的 SWD 与手术损伤有关，而不是与 FPI 特异性相关。ETX 显著抑制单侧或双侧起始的 SWD，而 CBZ 对两种类型的 SWD 均无影响。这些结果表明，无论是单侧起始还是双侧起始的 SWD 均具有与失神发作相似的药物敏感性，与 PTE 的复杂部分性发作有很大不同。因此，FPI 后单侧起始的 SWD 不是 PTE 中复杂部分性发作的模型，使用其寻找新的 PTE 治疗方法可能适得其反，特别是如果不承认其与正常脑电波的密切相似性。与被认为反映人类失神发作的双侧起始 SWD 相比，大鼠单侧起始的 SWD 已被用于模拟人类创伤后癫痫（PTE）中的复杂部分性发作。在这里，我们发现创伤性脑损伤后无论是单侧起始还是双侧起始的 SWD 均被抗失神药物乙琥胺抑制，而不受抗癫痫药物卡马西平的影响。我们提出，单侧起始的 SWD 对于研究 PTE 的机制或治疗方法没有用处。
