Intranasal Administration of MSC‐Derived Exosomes Modulate Status Epilepticus Induced Abnormal Plasticity of Newly Born Neurons and Microglial Activation in the Hippocampus
Abstract
Status epilepticus (SE) is a self‐sustaining seizure episode that causes adverse alterations in the hippocampus, which lead to a state of chronic epilepsy. We investigated the effects of mesenchymal stem cell (MSC)‐derived exosomes (small extracellular vesicles, EVs) to ameliorate the most prominent early changes induced by SE such as the abnormal plasticity of newly born neurons and activation of microglia. F344 rats were subjected to Kainic‐acid‐induced SE for 2 hours and then intranasally treated with a dose of exosomes (100 billion) or vehicle (VEH). In animals receiving VEH after SE (n=5), 20% of double cortin (DCX)‐positive newly born neurons displayed basal dendrites at 7 days post‐SE. Furthermore, the percentage of microglia with ramified morphology (resting microglia) was severely depleted in the CA1 subfield (6%) of these animals because of their activation. In contrast, in animals receiving EVs after SE (n=8), only 5% of DCX+ newly born neurons exhibited basal dendrites (p<0.0001). Also, these animals displayed a higher percentage (20%) of ramified microglia than animals receiving VEH, implying a reduced level of activation (p< 0.05). Thus, intranasal administration of MSC‐derived exosomes after SE is efficient for dampening the abnormal plasticity of newly born neurons and modulating microglial activation in the hippocampus. Basal dendrites promote abnormal connectivity between dentate granule cells and hilar/CA3 pyramidal neurons, as well as enhance granule cell to granule cell connectivity. Since both abnormal plasticity and neuroinflammation contribute to the occurrence of spontaneous seizures in the chronic phase, the results have significance.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.557.4
Entities
People
- Ashok K. Shetty
- Daniel Gitai
- Darwin J. Prockop
- Dong Ki Kim
- Maheedhar Kodali
- Mariam Adebola Atobiloye
- Sahithi Attaluri
Organizations
- United States Department of Defense