Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Qianfa Longa, Dinesh Upadhya, Bharathi Hattiangady, Dong Ki Kim, Su Yeon An, Bing Shuai, Darwin J. Prockop, Ashok K. Shetty

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrowderived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties. We subjected young mice to pilocarpine-induced SE for 2 h and then administered A1-exosomes or vehicle IN twice over 24 h. The A1-exosomes reached the hippocampus within 6 h of administration, and animals receiving them exhibited diminished loss of glutamatergic and GABAergic neurons and greatly reduced inflammation in the hippocampus. Moreover, the neuroprotective and antiinflammatory effects of A1-exosomes were coupled with long-term preservation of normal hippocampal neurogenesis and cognitive and memory function, in contrast to waned and abnormal neurogenesis, persistent inflammation, and functional deficits in animals receiving vehicle. These results provide evidence that IN administration of A1-exosomes is efficient for minimizing the adverse effects of SE in the hippocampus and preventing SE-induced cognitive and memory impairments.

Original languageEnglish
Pages (from-to)E3536-E3545
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number17
DOIs
Publication statusPublished - 25-04-2017

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Exosomes
Status Epilepticus
Neurogenesis
Mesenchymal Stromal Cells
Inflammation
Hippocampus
Intranasal Administration
Anti-Inflammatory Agents
GABAergic Neurons
Pilocarpine
Memory Disorders
Neuroprotective Agents
Anticonvulsants
Cognition
Emergencies
Bone and Bones

All Science Journal Classification (ASJC) codes

  • General

Cite this

Longa, Qianfa ; Upadhya, Dinesh ; Hattiangady, Bharathi ; Kim, Dong Ki ; An, Su Yeon ; Shuai, Bing ; Prockop, Darwin J. ; Shetty, Ashok K. / Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 17. pp. E3536-E3545.
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Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. / Longa, Qianfa; Upadhya, Dinesh; Hattiangady, Bharathi; Kim, Dong Ki; An, Su Yeon; Shuai, Bing; Prockop, Darwin J.; Shetty, Ashok K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 17, 25.04.2017, p. E3536-E3545.

Research output: Contribution to journalArticle

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AU - Longa, Qianfa

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AU - Kim, Dong Ki

AU - An, Su Yeon

AU - Shuai, Bing

AU - Prockop, Darwin J.

AU - Shetty, Ashok K.

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