Impaired functional recovery of endothelial colony-forming cells from moyamoya disease in a chronic cerebral hypoperfusion rat model

Seung Ah Choi, Sangjoon Chong, Pil Ae Kwak, Youn Joo Moon, Anshika Jangra, Ji Hoon Phi, Ji Yeoun Lee, Sung Hye Park, Seung Ki Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

OBJECTIVE Endothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model. METHODS A CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies. RESULTS The normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups. CONCLUSIONS These results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.

Original languageEnglish
Pages (from-to)204-213
Number of pages10
JournalJournal of Neurosurgery: Pediatrics
Volume23
Issue number2
DOIs
StatePublished - Feb 2019

Fingerprint

Moyamoya Disease
Cerebrovascular Circulation
Cisterna Magna
Flowmeters
Myelin Basic Protein
Common Carotid Artery
Glial Fibrillary Acidic Protein
Neurogenesis
von Willebrand Factor
Hematoxylin
Eosine Yellowish-(YS)
Caspase 3
Cognition
Fluorescent Antibody Technique
Ligation
Hippocampus

Keywords

  • Chronic cerebral hypoperfusion
  • Endothelial colony-forming cells
  • Moyamoya disease
  • Rat model
  • Vascular disorders

Cite this

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title = "Impaired functional recovery of endothelial colony-forming cells from moyamoya disease in a chronic cerebral hypoperfusion rat model",
abstract = "OBJECTIVE Endothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model. METHODS A CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies. RESULTS The normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups. CONCLUSIONS These results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.",
keywords = "Chronic cerebral hypoperfusion, Endothelial colony-forming cells, Moyamoya disease, Rat model, Vascular disorders",
author = "Choi, {Seung Ah} and Sangjoon Chong and Kwak, {Pil Ae} and Moon, {Youn Joo} and Anshika Jangra and Phi, {Ji Hoon} and Lee, {Ji Yeoun} and Park, {Sung Hye} and Kim, {Seung Ki}",
year = "2019",
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language = "English",
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pages = "204--213",
journal = "Journal of Neurosurgery: Pediatrics",
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Impaired functional recovery of endothelial colony-forming cells from moyamoya disease in a chronic cerebral hypoperfusion rat model. / Choi, Seung Ah; Chong, Sangjoon; Kwak, Pil Ae; Moon, Youn Joo; Jangra, Anshika; Phi, Ji Hoon; Lee, Ji Yeoun; Park, Sung Hye; Kim, Seung Ki.

In: Journal of Neurosurgery: Pediatrics, Vol. 23, No. 2, 02.2019, p. 204-213.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impaired functional recovery of endothelial colony-forming cells from moyamoya disease in a chronic cerebral hypoperfusion rat model

AU - Choi, Seung Ah

AU - Chong, Sangjoon

AU - Kwak, Pil Ae

AU - Moon, Youn Joo

AU - Jangra, Anshika

AU - Phi, Ji Hoon

AU - Lee, Ji Yeoun

AU - Park, Sung Hye

AU - Kim, Seung Ki

PY - 2019/2

Y1 - 2019/2

N2 - OBJECTIVE Endothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model. METHODS A CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies. RESULTS The normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups. CONCLUSIONS These results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.

AB - OBJECTIVE Endothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model. METHODS A CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies. RESULTS The normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups. CONCLUSIONS These results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.

KW - Chronic cerebral hypoperfusion

KW - Endothelial colony-forming cells

KW - Moyamoya disease

KW - Rat model

KW - Vascular disorders

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DO - 10.3171/2018.8.PEDS1883

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