Introduction: Trans-arterial administration of mesenchymal stem cells (MSCs) has been demonstrated to reduce infarct size and improve functional recovery following stroke. We tested the hypothesis that reversible opening of the blood-brain barrier (BBB) by sphenopalatine ganglion (SPG) stimulation enhances graft survival and recovery.
Methods: Sprague-Dawley rats (n=30) underwent induced ischemia by middle cerebral artery occlusion (MCAO). The negative control group (n=6) underwent MCAO alone. Twenty-four hours following MCAO, remaining animals were injected with 1x106 male rat MSCs into the ipsilateral internal carotid artery. Cells were cultured from bone marrow of transgenic S-D rats with germline expression of green fluorescent protein (GFP+). Positive controls (n=12) underwent MSC infusion alone. Immediately prior to MSC infusion, the experimental group (n=12) underwent bipolar stimulation of postganglionic parasympathetic fibers of the SPG within the orbit to selectively open the ipsilateral BBB.
Results: : Rats underwent functional testing until post-stroke day 14 and were subsequently sacrificed. Direct fluorescence of GFP+ cells and enhanced immunofluorescence with anti-GFP was used to track infused cells. Functional testing (including modified neurologic severity score), infarct volume, and histologic differentiation of MSCs into glial, neuronal and microglial phenotypes co-localizing with GFP positivity between each of three groups will be presented.
Conclusions: Early results suggest SPG stimulation-mediated BBB modulation may enhance the graft yield of trans-arterial cellular therapy. The future implications of SPG stimulation for blood-brain barrier modulation in the setting of cellular therapy will also be discussed.
Patient Care: This model for BBB modulation offers substantial potential for drug and cellular therapy in combination with the selectivity of endovascular delivery.
Learning Objectives: Discuss BBB modulation as a potential modality for enhanced trans-arterial delivery by sphenopalatine ganglion stimulation.
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