Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain
Abstract
Cranial irradiation used during the clinical management of brain cancer is associated with severe cognitive decline and represents a particular concern for pediatric cancer survivors. Irradiation triggers neuroinflammation and compromises the structure of neurons, factors that are contributory if not causal to radiation-induced cognitive dysfunction. Our previous data have shown that intrahippocampal transplantation of human neural stem cells (hNSCs) could ameliorate radiation-induced behavioral deficits and improve neuronal plasticity. These beneficial neurocognitive effects were hypothesized to act through a trophic support mechanism involving the secretion of microvesicles acting on host neuronal circuitry. Here we show that cranial grafting of hNSC-derived microvesicles reverses or prevents radiation-induced cognitive dysfunction through mechanisms involving the suppression of inflammation and the preservation of host neuronal architecture.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 04, 2016
- Source ID
- 10.1073/pnas.1521668113
Entities
People
- Amber Syage
- Audrey L. Park
- Barrett D. Allen
- Charles L. Limoli
- Erich Giedzinski
- Janet E. Baulch
- Munjal M. Acharya
- Nicole N. Chmielewski
- Ning Ru
- Sarah N. Benke
- Vahan Martirosian
- Vipan K. Parihar
Organizations
- Defense Threat Reduction Agency
- National Institute of Neurological Disorders and Stroke
- University of California