Platelets promote epileptic seizures by modulating brain serotonin level, enhancing neuronal electric activity, and contributing to neuroinflammation and oxidative stress
| Autor: | Amanda W. Y. Yung, Tatyana Veremeyko, Kseniia Levchuk, Thomas Y.B. Lau, Ekaterina Kopeikina, Inna S. Kuznetsova, Marina Dukhinova, Eugene D. Ponomarev |
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| Rok vydání: | 2020 |
| Předmět: |
Blood Platelets
0301 basic medicine Serotonin Traumatic brain injury Central nervous system Mice Transgenic Oxidative phosphorylation medicine.disease_cause Mice 03 medical and health sciences Epilepsy 0302 clinical medicine Seizures Gangliosides medicine Animals Platelet Neuroinflammation Inflammation business.industry General Neuroscience Brain medicine.disease Mice Inbred C57BL Disease Models Animal Oxidative Stress 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier business Neuroscience 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Progress in Neurobiology. 188:101783 |
| ISSN: | 0301-0082 |
| DOI: | 10.1016/j.pneurobio.2020.101783 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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