title: Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral haemorrhage in mice.
abstract: We investigated the role of matrix metalloproteinases (MMPs) in a mouse model of intracerebral haemorrhage (ICH). Transcripts encoding nine of the 23 known mammalian MMPs were measured. MMP-12 levels were the most elevated. To evaluate the role of MMP-12 in ICH, haemorrhages were induced in wild-type (WT) and MMP-12 null mice. The results show that MMP-12 null mice exhibited significant functional recovery of forelimb reaching and reduced dependence on the ipsilateral forelimb compared to WT mice. There was also a trend for improved sensory function in the tape removal test. With respect to single pellet skilled reaching, MMP-12 null mice recovered to a level that was not significantly different from sham at 14 and 28 days post-ICH. In contrast, WT animals demonstrated a persistent impairment relative to sham controls throughout the survival period (P < 0.05). The cylinder task revealed a lesion-induced reliance on the ipsilateral forelimb that was apparent at day 7 in both MMP-12 null and WT mice (P < 0.05), but only persisted in WT mice at 14 days post-ICH (P < 0.05). Differences in functional outcome could not be explained by tissue sparing. However, Iba1 immunostaining indicated that more cells bearing macrophage morphology were recruited to the lesion area in WT mice. This is the first study to profile the expression patterns of a number of the known MMPs following ICH in mice. The data indicate that MMP-12 expression following haemorrhagic stroke is deleterious and contributes to the development of secondary injury in this disease.
authors.affiliation: Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Jennifer E A
authors.initials: JE
authors.lastname: Wells
authors.forename: Jeff
authors.initials: J
authors.lastname: Biernaskie
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szymanska
authors.forename: Peter H
authors.initials: PH
authors.lastname: Larsen
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.forename: Dale
authors.initials: D
authors.lastname: Corbett
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015152:Blotting, Northern / Q000379:methods; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000503:physiopathology*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D008264:Macrophages / Q000473:pathology; D008297:Male; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D017628:Microglia / Q000473:pathology; D011597:Psychomotor Performance / Q000502:physiology*; D012313:RNA / Q000032:analysis; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors
chemical_list: D012313:RNA; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12