Barker-Haliski Melissa L, Löscher Wolfgang, White H Steve, Galanopoulou Aristea S
Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, Washington, U.S.A.
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
Epilepsia. 2017 Jul;58 Suppl 3(Suppl 3):39-47. doi: 10.1111/epi.13785.
Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis-induced epilepsy. Rat models of infantile spasms were generated in rat pups after right intracerebral injections of proinflammatory compounds (lipopolysaccharides with or without doxorubicin, or cytokines) and were longitudinally monitored for epileptic spasms and neurodevelopmental and cognitive deficits. Anti-inflammatory treatments were tested after the onset of spasms. The TMEV mouse model was induced with intracerebral administration of TMEV and prospective monitoring for handling-induced seizures or seizure susceptibility, as well as long-term evaluations of behavioral comorbidities of epilepsy. Inflammatory processes are evident in both models and are implicated in the pathogenesis of the observed seizures and comorbidities. A common feature of these models, based on the data so far available, is their pharmacoresistant profile. The presented data support the role of inflammatory pathways in epileptogenesis and comorbidities in two distinct epilepsy models. Pharmacoresistance is a common feature of both inflammation-based models. Utilization of these models may facilitate the identification of age-specific, syndrome- or etiology-specific therapies for the epilepsies and attendant comorbidities, including the drug-resistant forms.
动物模型为癫痫发生机制和共病发生机制提供了丰富的信息，并显著提升了我们研究新疗法潜力的能力。在癫痫研究中，越来越多地观察到涉及脑炎症的过程。在此，我们讨论癫痫和共病动物模型的进展，这些模型让我们了解炎症在韦斯特综合征啮齿动物模型以及病毒性脑炎诱导癫痫的泰勒氏鼠脑脊髓炎病毒（TMEV）小鼠模型的癫痫发生和共病发病机制中的潜在作用。在幼鼠右侧脑内注射促炎化合物（脂多糖加或不加阿霉素，或细胞因子）后建立婴儿痉挛大鼠模型，并对癫痫痉挛、神经发育和认知缺陷进行纵向监测。在痉挛发作后测试抗炎治疗。通过脑内注射TMEV诱导TMEV小鼠模型，并对处理诱导的癫痫发作或癫痫易感性进行前瞻性监测，以及对癫痫的行为共病进行长期评估。在这两种模型中炎症过程都很明显，并且与观察到的癫痫发作和共病的发病机制有关。根据目前可得的数据，这些模型的一个共同特征是它们的药物抵抗特征。所呈现的数据支持炎症途径在两种不同癫痫模型的癫痫发生和共病中的作用。药物抵抗是这两种基于炎症的模型的共同特征。利用这些模型可能有助于确定针对癫痫及其伴随共病（包括耐药形式）的年龄特异性、综合征或病因特异性疗法。
