The drugs currently available for treating epilepsy are only partially effective in managing this condition. Therefore, it is crucial to investigate new pathways that induce and promote epilepsy development. Previously, we found that platelets interact with neuronal glycolipids and actively secrete pro-inflammatory mediators during central nervous system (CNS) pathological conditions such as neuroinflammation and traumatic brain injury (TBI). These factors increase the permeability of the blood-brain barrier (BBB), which may create a predisposition to epileptic seizures. In this study, we demonstrated that platelets substantially enhanced epileptic seizures in a mouse model of pentylenetetrazole (PTZ) -induced seizures. We found that platelets actively secreted serotonin, contributed to increased BBB permeability, and were present in the CNS parenchyma during epileptic seizures. Furthermore, platelets directly stimulated neuronal electric activity and induced the expression of specific genes related to early neuronal response, neuroinflammation, and oxidative phosphorylation, leading to oxidative stress in neurons. The intracranial injection of physiological numbers of platelets that mimicked TBI-associated bleeding was sufficient to induce severe seizures, which resembled conventional PTZ-induced epileptic activity. These findings highlight a conceptually new role of platelets in the development of epileptic seizures and indicate a potential new therapeutic approach, targeting platelets to prevent and treat epilepsy.

当前可用于治疗癫痫的药物仅能部分有效地治疗这种情况。因此，研究诱导和促进癫痫发展的新途径至关重要。以前，我们发现血小板与神经元糖脂相互作用，并在中枢神经系统（CNS）病理状况（例如神经发炎和颅脑外伤（TBI））期间主动分泌促炎性介质。这些因素会增加血脑屏障（BBB）的通透性，这可能会导致癫痫发作。在这项研究中，我们证明了血小板在戊四氮（PTZ）诱发的癫痫发作小鼠模型中显着增强了癫痫发作。我们发现血小板主动分泌5-羟色胺，导致血脑屏障通透性增加，并且在癫痫发作期间存在于CNS实质中。此外，血小板直接刺激神经元的电活动并诱导与早期神经元反应，神经炎症和氧化磷酸化有关的特定基因的表达，从而导致神经元的氧化应激。颅内注射模仿TBI相关性出血的生理数量的血小板足以诱发严重的癫痫发作，类似于常规的PTZ诱发的癫痫活动。这些发现突出了血小板在癫痫发作发展中的概念上新的作用，并表明了潜在的新治疗方法，将血小板靶向于预防和治疗癫痫。血小板直接刺激神经元电活动并诱导与早期神经元反应，神经炎症和氧化磷酸化有关的特定基因的表达，从而导致神经元的氧化应激。颅内注射模仿TBI相关性出血的生理数量的血小板足以诱发严重的癫痫发作，类似于常规的PTZ诱发的癫痫活动。这些发现突出了血小板在癫痫发作发展中的概念上新的作用，并表明了潜在的新治疗方法，将血小板靶向于预防和治疗癫痫。血小板直接刺激神经元电活动并诱导与早期神经元反应，神经炎症和氧化磷酸化有关的特定基因的表达，从而导致神经元的氧化应激。颅内注射模仿TBI相关性出血的生理数量的血小板足以诱发严重的癫痫发作，类似于常规的PTZ诱发的癫痫活动。这些发现突出了血小板在癫痫发作发展中的概念上新的作用，并表明了潜在的新治疗方法，将血小板靶向于预防和治疗癫痫。颅内注射模仿TBI相关性出血的生理数量的血小板足以诱发严重的癫痫发作，类似于常规的PTZ诱发的癫痫活动。这些发现突出了血小板在癫痫发作发展中的概念上新的作用，并表明了潜在的新治疗方法，将血小板靶向于预防和治疗癫痫。颅内注射模仿TBI相关性出血的生理数量的血小板足以诱发严重的癫痫发作，类似于常规的PTZ诱发的癫痫活动。这些发现突显了血小板在癫痫性发作发展中的概念上新的作用，并表明了潜在的新治疗方法，将血小板靶向于预防和治疗癫痫。