Abstract

During subarachnoid hemorrhage (SAH) blood flows into the subarachnoid space of the brain as a result of a ruptured blood vessel. The mortality rate of SAH is approximately 40–50% and surviving patients are confronted with a great loss of quality of life. SAH occurs at a relatively young age and has an unpredictable onset. There are only limited therapeutic options and unfortunately these treatments have a short time window. We studied the therapeutic effects of intranasal mesenchymal stem cell transplantation (MSC) in the endovascular puncture model in the rat. SAH induces long-term brain damage through loss of grey and white matter which is located mainly in the cortex. Moreover, SAH is associated with cerebral inflammation as shown by cytokine mRNA expression and microglia/astrocyte activation 3 weeks after SAH. Furthermore, sensory motor function as observed in the adhesive removal test was decreased as well as mechanical sensitivity of the hind paws as shown by von Frey testing. Interestingly, SAH also decreased sucrose preference. Intranasal administration of MSC 6 days after SAH decreased brain lesion volume and downregulated cerebral inflammation. MSC treatment improved sensori-motor behavior and mechanical sensitivity of the paws. Moreover, sucrose preference was restored to the level of sham-operated animals. Conclusion: Intranasal MSC transplantation restores brain damage, and sensori-motor function and reduces longterm cerebral inflammation and depressive-like behavior in animals subjected to SAH.

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