title: Zinc Protoporphyrin Attenuates White Matter Injury after Intracerebral Hemorrhage.
abstract: Intracerebral hemorrhage (ICH)-induced white matter injury has not been well studied. The objective of this study was to examine the effect of zinc protoporphyrin (ZnPP) on white matter injury induced by ICH. This study was divided into two parts. In the first part, rats received either a needle insertion (sham) or 100 μl autologous blood into the right basal ganglia. The rats were euthanized at 1, 3, 7, 14, or 28 days later for myelin basic protein (MBP) measurement. In the second part, rats had intracerebral infusion of 100 μl autologous blood, and an intraperitoneal osmotic mini-pump was implanted immediately after ICH to deliver vehicle or ZnPP (1 nmol/h), a heme oxygenase inhibitor, for up to 14 days. Rats were euthanized at day 28 for MBP staining. The number of MBP-labeled fiber bundles and their area were determined. The time-course showed that the white matter was lost in the ipsilateral basal ganglia from day 1 to day 28 after ICH. The number of MBP-labeled bundles and their area were significantly lower 2 weeks after ICH compared with sham-operated rats (p < 0.05). Systemic treatment with ZnPP attenuated the loss of MBP-labeled bundles (p < 0.01) and area (p < 0.01). In conclusion, marked white matter injury occurs after ICH. ZnPP reduces white matter injury, suggesting a role of heme degradation products in ICH-induced white matter damage.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. yahua@umich.edu.|R5005, BSRB, University of Michigan, Ann Arbor, MI, 48109, USA. yahua@umich.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D008297:Male; D004676:Myelin Basic Protein / Q000187:drug effects* / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D066127:White Matter / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D004676:Myelin Basic Protein; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006419:Heme Oxygenase (Decyclizing)
keywords: Heme oxygenase; Intracerebral hemorrhage; White matter injury; Zinc protoporphyrin