TY - JOUR
T1 - Intranasal Stem Cell Treatment as a Novel Therapy for Subarachnoid Hemorrhage
AU - Nijboer, Cora H.
AU - Kooijman, Elke
AU - Van Velthoven, Cindy T.
AU - Van Tilborg, Erik
AU - Tiebosch, Ivo A.
AU - Eijkelkamp, Niels
AU - Dijkhuizen, Rick M.
AU - Kesecioglu, Jozef
AU - Heijnen, Cobi J.
N1 - Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
KW - depression-like behavior
KW - intranasal treatment
KW - mesenchymal stem cells
KW - neuroinflammation
KW - neuroregeneration
KW - subarachnoid hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=85042882497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042882497&partnerID=8YFLogxK
U2 - 10.1089/scd.2017.0148
DO - 10.1089/scd.2017.0148
M3 - Article
C2 - 29310519
AN - SCOPUS:85042882497
SN - 1547-3287
VL - 27
SP - 313
EP - 325
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 5
ER -