Nasal Administration of Amniotic Mesenchymal Stem Cell-Derived Exosomes Alleviates Neurological Impairment in a Subarachnoid Hemorrhage Animal Model

Introduction: Subarachnoid hemorrhage (SAH) is a type of stroke caused by the rupture of an intracranial aneurysm. However, there is currently no established treatment for directly ameliorating the inflammation and apoptosis occurring in the damaged brain. Mesenchymal stem cell (MSC)-derived exosomes, containing miRNAs and believed to have anti-apoptotic and anti-neuroinflammatory effects post-brain injury, face limitations in their ability to reach the brain due to their distribution and the blood-brain barrier when conventionally administered via intravenous routes. In this study, we aimed to investigate whether intranasal administration of MSC-derived exosomes could lead to functional improvement in an SAH model animal.

Methods: Exosomes were obtained from the culture supernatant of amniotic membrane-derived MSCs provided by Kaneka Corporation through ultra-centrifugation. Their characteristics, including surface antigens, size distribution, and electron microscopy, were confirmed. For the SAH model, adult male Sprague-Dawley rats received autologous blood injections into the prechiasmatic cistern. Immediately after hemorrhage induction and the following day, rats were intranasally administered either 1.2x10e10 exosomes diluted in 200uL of phosphate-buffered saline (PBS) or 200uL of PBS alone. Motor function was assessed using the Open Field Test (OFT) up to seven days post-SAH. On the 7th day, animals were sacrificed, and apoptosis was assessed using Apoptag®, neuronal loss with NeuN staining, and neuroinflammation with Iba1 staining.

Results: Compared to the PBS group, the exosome intranasal administration group exhibited a significant reduction in abnormal exploratory behavior in the OFT. Apoptosis in the hippocampal CA1 region was notably suppressed in the exosome group. Additionally, exosome intranasal administration significantly inhibited neuronal loss and neuroinflammation in the same region.

Conclusion : Intranasal administration of MSC-derived exosomes demonstrated a convenient and effective neuroprotective effect, suggesting its potential as a novel treatment for SAH.