The asparaginyl endopeptidase legumain after experimental stroke.
Various proteases in the brain contribute to ischemic brain injury. We investigated the involvement of the asparaginyl endopeptidase legumain after experimental stroke. On the basis of gene array studies and in situ hybridizations, we observed an increase of legumain expression in the peri-infarct area of rats after transient occlusion of the middle cerebral artery (MCAO) for 120 mins with a maximum expression at 24 and 48 h. Immunohistochemical analyses revealed the expression of legumain in Iba1(+) microglial cells and glial fibrillary acidic protein-positive astrocytes of the peri-infarct area in mice after MCAO. Post-stroke recovery was also studied in aged legumain-deficient mice (45 to 58 weeks old). Legumain-deficient mice did not show any differences in physiologic parameters compared with respective littermates before, during MCAO (45 mins), and the subsequent recovery period of 8 days. Moreover, legumain deficiency had no effect on mortality, infarct volume, and the neurologic deficit determined by the rotating pole test, a standardized grip strength test, and the pole test. However, a reduced number of invading CD74(+) cells in the ischemic hemisphere indicates an involvement in post-stroke inflammation. We conclude that legumain is not essential for the functional deficit after MCAO but may be involved in mechanisms of immune cell invasion.
Department of Clinical Sciences, Wallenberg Neuroscience Center, University of Lund, Sweden.
Taku
T
Ishizaki
Agnes
A
Erickson
Enida
E
Kuric
Mehrdad
M
Shamloo
Ikuko
I
Hara-Nishimura
Ana Rita Lourenço
AR
Inácio
Tadeusz
T
Wieloch
Karsten
K
Ruscher
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001253:Astrocytes / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000201:enzymology* / Q000473:pathology; D000099240:Asparaginyl Endopeptidase
D000944:Antigens, Differentiation, B-Lymphocyte; D003546:Cysteine Endopeptidases; D000949:Histocompatibility Antigens Class II; D000099240:Asparaginyl Endopeptidase; C045084:invariant chain