Stem Cells Dev. 2018 Jan 8. doi: 10.1089/scd.2017.0148. [Epub ahead of print]

Intranasal stem cell treatment as a novel therapy for subarachnoid hemorrhage.

Nijboer CH¹, Kooijman E², van Velthoven CT³, Van Tilborg E⁴, Tiebosch IA⁵, Eijkelkamp N⁶, Dijkhuizen RM⁷, Kesecioglu J⁸, Heijnen C⁹.

Abstract

Subarachnoid hemorrhage (SAH) represents a major health problem in Western society due to high mortality and morbidity, and the relative young age of patients. Currently, efficacious therapeutic options are very limited. Mesenchymal stem cell (MSC) administration has been shown to improve functional outcome and lesion size in experimental models of stroke and neonatal hypoxic-ischemic brain injury. Here we studied the therapeutic potential of intranasally administered bone marrow-derived MSCs relatively late post-insult using a rat endovascular puncture model for SAH. Six days after induction of SAH, rats were treated with MSCs or vehicle via nasal administration. Intranasal MSC treatment significantly improved sensorimotor and mechano-sensory function at 21 days after SAH. Gray and white matter loss was significantly reduced by MSC treatment and the number of NeuN+ neurons around the lesion increased due to MSC treatment. Moreover, intranasal MSC administration led to a sharp decrease in SAH-induced activation of astrocytes and microglia/macrophages in the lesioned hemisphere especially of M2-like (CD206+) microglia/macrophages. Interestingly, MSC administration also decreased SAH-induced depression-like behavior in association with a restoration of tyrosine-hydroxylase expression in the substantia nigra and striatum. We show here for the first time that intranasal MSC administration reverses the devastating consequences of SAH including regeneration of the cerebral lesion, functional recovery and treatment of co-morbid depression-like behavior.