title: Therapeutic Benefits of Mesenchymal Stromal Cells in a Rat Model of Hemoglobin-Induced Hypertensive Intracerebral Hemorrhage.
abstract: Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-1β and TNF-α). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.
authors.affiliation: Department of Neurosurgery, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Maoming People's Hospital, Maoming 525000, Guangdong, China.
authors.forename: Chunnan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Hematology, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: ShanShan
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Maoming People's Hospital, Maoming 525000, Guangdong, China.
authors.forename: Naichong
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Maoming People's Hospital, Maoming 525000, Guangdong, China.
authors.forename: Liangang
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Maoming People's Hospital, Maoming 525000, Guangdong, China.
authors.forename: Yumao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: XiaoWei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Jingmen No. 1 People's Hospital, Jingmen 448000, Hubei, China.
authors.forename: LiHua
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000378:metabolism; D020299:Intracranial Hemorrhage, Hypertensive / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011897:Random Allocation; D051381:Rats
chemical_list: D006454:Hemoglobins
keywords: ONOO−; hypertensive intracerebral hemorrhage; iNOS; mesenchymal stromal cells