title: A rat model of chronic subdural hematoma: Insight into mechanisms of revascularization and inflammation.
abstract: Chronic subdural hematoma (CSDH) is a common neurological occurrence in the elderly population with significant impact on the quality of life and work. Studies have attempted to determine the risk factors and pathophysiological mechanisms of CSDH using models in numerous mammalian species. To date, these animal models have only been able to reproduce limited durations of hematoma which does not accurately reflect the chronic state of CSDH. To address some of these challenges we modified a rat model of CSDH using two consecutive injections of autologous blood resulting in a hematoma of more than three weeks. We observed inflammatory and angiogenic changes related to the development and recovery of CSDH. In this study the technique for producing a CSDH in a small animal model had a success rate of 78.13%. The hematoma was sustainable up to 24 days. Hematoma resolution was associated with a gradual decrease in local pro-inflammatory factors and gradual increase in anti-inflammatory factors as well as proliferation and subsequent maturation of newly formed vessels. These events were also associated with improved behavioral outcome. Expression of anti-inflammatory cytokines also paralleled reabsorption of the hematoma. Reduction in hematoma size was also associated with neurological recovery. These data suggest that vessel maturation and anti-inflammatory pathways may contribute to the resolution of CSDH and neurological recovery. The regulation of the two mechanisms is a potential target for the treatment of CSDH. The modified model of rat CSDH demonstrated a high level of reproducibility in our hands and may be useful in future CSDH studies.
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China.
authors: Wei
authors: W
authors: Quan
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China.
authors: Zhifei
authors: Z
authors: Zhang
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China.
authors: Qilong
authors: Q
authors: Tian
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China.
authors: Xiaolong
authors: X
authors: Wen
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China.
authors: Peng
authors: P
authors: Yu
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China.
authors: Dong
authors: D
authors: Wang
authors: Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China.
authors: Weiyun
authors: W
authors: Cui
authors: Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China.
authors: Lei
authors: L
authors: Zhou
authors: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael׳s Hospital, Canada.
authors: Eugene
authors: E
authors: Park
authors: The Institute of Medical Science, Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada; The Institute of Medical Science, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors: Andrew J
authors: AJ
authors: Baker
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China. Electronic address: jianningzhangtj@gmail.com.
authors: Jianning
authors: J
authors: Zhang
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, 154 Anshan Road, Tianjin 300052, China; Tianjin Neurological Institute, 154 Anshan Road, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, 154 Anshan Road, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Tianjin 300052, China. Electronic address: rongcaijiang@gmail.com.
authors: Rongcai
authors: R
authors: Jiang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020200:Hematoma, Subdural, Chronic / Q000150:complications* / Q000473:pathology*; D007249:Inflammation / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D009460:Neurologic Examination; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; C029417:Von Willebrand antigen; D014841:von Willebrand Factor
keywords: Angiogenesis; Behavior; Chronic subdural hematoma; Histology; Inflammation; Pathology; Rat model