TY - JOUR
T1 - Cranial Bone Transport Promotes Angiogenesis, Neurogenesis, and Modulates Meningeal Lymphatic Function in Middle Cerebral Artery Occlusion Rats
AU - Bai, Shanshan
AU - Lu, Xuan
AU - Pan, Qi
AU - Wang, Bin
AU - Pong U, Kin
AU - Yang, Yongkang
AU - Wang, Haixing
AU - Lin, Sien
AU - Feng, Lu
AU - Wang, Yan
AU - Li, Yucong
AU - Lin, Weiping
AU - Wang, Yujia
AU - Zhang, Xiaoting
AU - Li, Yuan
AU - Li, Linlong
AU - Yang, Zhengmeng
AU - Wang, Ming
AU - Lee, Wayne Yuk Wai
AU - Jiang, Xiaohua
AU - Li, Gang
N1 - Funding Information:
This work was partially supported by grants from the Hong Kong Government Research Grant Council, General Research Fund (14120118, 14108720, T13-402/17-N‚ AoE/M-402/20); Hong Kong Medical Research Funds (16170951 and 17180831). This study also received support from the SMART (Sport Medicine and Regenerative Therapy) program, Lui Che Woo Institute of Innovative Medicine, and the Chinese University of Hong Kong.
Publisher Copyright:
© 2022 American Heart Association, Inc.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Background: Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using tissue-type plasminogen activator treatment is rather limited, resulting in many patients experiencing long-term functional impairments if not death. This study aims to determine the roles of cranial bone transport (CBT), a novel, effective, and simple surgical technique, in the recovery of ischemic stroke using middle cerebral artery occlusion (MCAO) rat model. Methods: CBT was performed by slowly sliding a bone segment in skull with a special frame and a speed of 0.25 mm/12 hours for 10 days following MCAO. Morris water maze, rotarod test, and catwalk gait analysis were used to study the neurological behaviors, and infarct area and cerebral flow were evaluated during CBT process. Immunofluorescence staining of CD31 and Nestin/Sox2 (sex determining region Y box 2) was performed to study the angiogenesis and neurogenesis. OVA-A647 (ovalbumin-Alexa Fluor 647) was intracisterna magna injected to evaluate the meningeal lymphatic drainage function. Results: CBT treatment has significantly reduced the ischemic lesions areas and improved the neurological deficits in MCAO rats compared with the rats in the control groups. CBT treatment significantly promoted angiogenesis and neurogenesis in the brain of MCAO rats. The drainage function of meningeal lymphatic vessels in MCAO rats was significantly impaired compared with normal rats. Ablation of meningeal lymphatic drainage led to increased neuroinflammation and aggravated neurological deficits and ischemic injury in MCAO rats. CBT treatment significantly improved the meningeal lymphatic drainage function and alleviated T-cell infiltration in MCAO rats. Conclusions: This study provided evidence for the possible mechanisms on how CBT attenuates ischemic stroke injury and facilitates rapid neuronal function recovery, suggesting that CBT may be an alternative treatment strategy for managing ischemic stroke.
AB - Background: Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using tissue-type plasminogen activator treatment is rather limited, resulting in many patients experiencing long-term functional impairments if not death. This study aims to determine the roles of cranial bone transport (CBT), a novel, effective, and simple surgical technique, in the recovery of ischemic stroke using middle cerebral artery occlusion (MCAO) rat model. Methods: CBT was performed by slowly sliding a bone segment in skull with a special frame and a speed of 0.25 mm/12 hours for 10 days following MCAO. Morris water maze, rotarod test, and catwalk gait analysis were used to study the neurological behaviors, and infarct area and cerebral flow were evaluated during CBT process. Immunofluorescence staining of CD31 and Nestin/Sox2 (sex determining region Y box 2) was performed to study the angiogenesis and neurogenesis. OVA-A647 (ovalbumin-Alexa Fluor 647) was intracisterna magna injected to evaluate the meningeal lymphatic drainage function. Results: CBT treatment has significantly reduced the ischemic lesions areas and improved the neurological deficits in MCAO rats compared with the rats in the control groups. CBT treatment significantly promoted angiogenesis and neurogenesis in the brain of MCAO rats. The drainage function of meningeal lymphatic vessels in MCAO rats was significantly impaired compared with normal rats. Ablation of meningeal lymphatic drainage led to increased neuroinflammation and aggravated neurological deficits and ischemic injury in MCAO rats. CBT treatment significantly improved the meningeal lymphatic drainage function and alleviated T-cell infiltration in MCAO rats. Conclusions: This study provided evidence for the possible mechanisms on how CBT attenuates ischemic stroke injury and facilitates rapid neuronal function recovery, suggesting that CBT may be an alternative treatment strategy for managing ischemic stroke.
KW - central nervous system
KW - inflammation
KW - ischemic stroke
KW - neurogenesis
UR - http://www.scopus.com/inward/record.url?scp=85127932731&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.121.037912
DO - 10.1161/STROKEAHA.121.037912
M3 - Article
C2 - 35135326
AN - SCOPUS:85127932731
SN - 0039-2499
VL - 53
SP - 1373
EP - 1385
JO - Stroke
JF - Stroke
IS - 4
ER -