Intranasal Stem Cell Treatment as a Novel Therapy for Subarachnoid Hemorrhage

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 postinsult using a rat endovascular puncture model for SAH. Six days after induction of SAH, rats were treated with MSCs or vehicle through nasal administration. Intranasal MSC treatment significantly improved sensorimotor and mechanosensory 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 comorbid depression-like behavior.

Cisplatin treatment induces attention deficits and impairs synaptic integrity in the prefrontal cortex in mice

“…Thirty minutes later mice received MSCs applied as 2 doses of 3 µL to each nostril (total volume of 12 µL with 10 6 cells per mouse per day 29 , 30 ) or PBS. We selected this schedule on the basis of our previous work in models of ischemic brain damage 30 – 33 . Three days before returning to the 5CSRTT training, mice were put back on the food-restriction schedule.…”

Application of olfactory ensheathing cells in clinical treatment of spinal cord injury: meta-analysis and prospect

“…In order to reduce the adverse reactions, future clinical research should carefully grasp the preoperative indications and try to explore a minimally invasive and effective transplantation method. A large number of animal studies have shown that intranasal delivery is a safe, minimally invasive and effective method for cell transplantation [42][43][44][45]. However, it has not been reported in clinical practices.…”

Recent Advances in Stem Cell Research in Subarachnoid Hemorrhage

“…Nasal administration is less invasive than the intracerebral route for the delivery of MSCs to the brain. MSCs migrated from the cribriform plate in the direction of the ipsilateral cerebral lesion site in 2-24 h. Nijboer CH and his teammates showed that intranasal administration of MSCs 6 days after severe SAH enhanced sensorimotor function and decreased the size of the lesion in rats [56]. Furthermore, there was a reduction in neuroinflammation as indicated by astrocyte and microglia/ macrophage activation.…”