Baker Tamara L, Wright David K, Thergarajan Peravina, Uboldi Alessandro D, Vo Anh, Wilson Trevor, Tonkin Christopher J, O'Brien Terence J, Antonic-Baker Ana, Asmussen Michael J, McDonald Stuart J, Casillas-Espinosa Pablo M, Jones Nigel C, Ali Idrish, Sun Mujun, Shultz Sandy R
Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC 3004, Australia.
Division of Infection and Global Health, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, VIC 3010, Australia.
Brain Behav Immun. 2025 Aug;128:440-455. doi: 10.1016/j.bbi.2025.04.026. Epub 2025 Apr 21.
There is initial evidence that the common neurotropic parasite Toxoplasma gondii is a risk factor for the development of epilepsy; however, whether it influences epileptogenesis is unknown. This study investigated whether a pre-existing chronic T. gondii infection alters epileptogenesis and neuropathology in a mouse model of mesial temporal lobe epilepsy.
Male and female C57BL/6Jax mice were intraperitoneally administered T. gondii tachyzoites or vehicle control. After 6 weeks, mice underwent self-sustained electrical status epilepticus (SSSE) through an implanted bipolar electrode, or a sham procedure. Continuous video-EEG recordings were taken 0-4- and 12-16-weeks post-SSSE to detect spontaneous seizures. Neuroinflammatory markers were assessed within 1-week post-SSSE, behavior testing was done at 8-12 weeks post-SSSE, and ex vivo MRI was conducted at 16 weeks post-SSSE.
Male T. gondii + SSSE mice had an increased incidence of epilepsy compared to Vehicle + SSSE, while female T. gondii + SSSE mice had worse seizure severity compared to non-infected SSSE mice. There was amplified neuroinflammation in both male and female T. gondii + SSSE mice compared to Vehicle + SSSE mice. T. gondii infection in the absence of SSSE also resulted in epilepsy and neuroinflammation. MRI revealed abnormalities in brain morphology in T. gondii + SSSE male and female mice and changes in white matter integrity in male T. gondii + SSSE mice, compared to both non-infected SSSE and T. gondii control mice. SSSE and T. gondii infection impacted anxiety and spatial memory in males, and anxiety and social behavior in females.
These findings demonstrate that a chronic T. gondii infection can result in epilepsy, and that a pre-existing T. gondii infection exacerbates epileptogenesis following a brain insult, in mice.
有初步证据表明，常见的嗜神经性寄生虫刚地弓形虫是癫痫发病的一个危险因素；然而，它是否影响癫痫发生尚不清楚。本研究调查了预先存在的慢性刚地弓形虫感染是否会改变内侧颞叶癫痫小鼠模型中的癫痫发生和神经病理学。
对雄性和雌性C57BL/6Jax小鼠腹腔注射刚地弓形虫速殖子或赋形剂对照。6周后，通过植入的双极电极对小鼠进行自持续癫痫持续状态（SSSE）诱导，或进行假手术。在SSSE后0 - 4周和12 - 16周进行连续视频脑电图记录以检测自发性癫痫发作。在SSSE后1周内评估神经炎症标志物，在SSSE后8 - 12周进行行为测试，并在SSSE后16周进行离体MRI检查。
与赋形剂 + SSSE组相比，雄性刚地弓形虫 + SSSE小鼠癫痫发病率增加，而雌性刚地弓形虫 + SSSE小鼠癫痫发作严重程度比未感染的SSSE小鼠更严重。与赋形剂 + SSSE小鼠相比，雄性和雌性刚地弓形虫 + SSSE小鼠的神经炎症均有所加剧。在没有SSSE的情况下，刚地弓形虫感染也会导致癫痫和神经炎症。MRI显示，与未感染的SSSE小鼠和刚地弓形虫对照小鼠相比，雄性和雌性刚地弓形虫 + SSSE小鼠的脑形态存在异常，雄性刚地弓形虫 + SSSE小鼠的白质完整性发生改变。SSSE和刚地弓形虫感染影响雄性的焦虑和空间记忆，以及雌性的焦虑和社交行为。
这些发现表明，慢性刚地弓形虫感染可导致癫痫，并且预先存在的刚地弓形虫感染会加剧小鼠脑损伤后的癫痫发生。
