title: Effects of Aerobic Capacity on Thrombin-Induced Hydrocephalus and White Matter Injury.
abstract: We have previously shown that intracerebral hemorrhage-induced brain injury is less in rats bred for high aerobic capacity (high capacity runners; HCR) compared with those bred for low aerobic capacity (low capacity runners; LCRs). Thrombin, an essential component in the coagulation cascade, is produced after cerebral hemorrhage. Intraventricular injection of thrombin causes significant hydrocephalus and white matter damage. In the present study, we examined the effect of exercise capacity on thrombin-induced hydrocephalus and white matter damage. Mid-aged (13-month-old) female LCRs (n = 13) and HCRs (n = 12) rats were used in this study. Rats received an intraventricular injection of thrombin (3 U, 50 μl). All rats underwent magnetic resonance imaging (MRI) at 24 h and were then euthanized for brain histology and Western blot. The mortalities were 20 % in LCRs and 33 % in HCRs after thrombin injection (p > 0.05). No rats died after saline injection. Intraventricular thrombin injection resulted in hydrocephalus and periventricular white matter damage as determined on MRI. In LCR rats, thrombin induced significant ventricle enlargement (23.0 ± 2.3 vs12.8 ± 1.9 mm(3) in LCR saline group; p < 0.01) and white matter lesion (9.3 ± 7.6 vs 0.6 ± 0.5 mm(3) in LCR saline group, p < 0.05). In comparison, in HCR rats thrombin induced less ventricular enlargement (17.3 ± 3.9 vs 23.0 ± 2.3 mm(3) in LCRs, p < 0.01) and smaller white matter lesions (2.6 ± 1.2 mm(3) vs 9.3 ± 7.6 mm(3) in LCRs, p < 0.05). In LCR rats, there was also upregulation of heat shock protein-32, a stress marker, and microglial activation in the periventricular white matter. These changes were significantly reduced in HCR rats. Intraventricular injection of thrombin caused more white matter damage and hydrocephalus in rats with low aerobic capacity. A differential effect of thrombin may contribute to differences in the effects of cerebral hemorrhage with aerobic capacity.
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.|Department of Neurology, the 2nd Affiliate Hospital, Zhejiang University, Zhejiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA. yahua@umich.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging*; D017079:Exercise Tolerance; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism; D006490:Hemostatics / Q000633:toxicity; D006849:Hydrocephalus / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D010805:Physical Conditioning, Animal; D051381:Rats; D013917:Thrombin / Q000633:toxicity; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D006490:Hemostatics; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D013917:Thrombin
keywords: Heat shock protein-32; Hydrocephalus; Microglia; Thrombin; White matter damage