Neuroprotective effects of HSP70 overexpression after cerebral ischaemia - An MRI study

被引:66
作者
van der Weerd, L
Lythgoe, MF
Badin, RA
Valentim, LM
Akbar, MT
de Belleroche, JS
Latchman, DS
Gadian, DG
机构
[1] UCL, RCS Unit Biophys, Inst Child Hlth, London WC1N 1EH, England
[2] UCL, Med Mol Biol Unit, Inst Child Hlth, London WC1N 1EH, England
[3] Charing Cross Hosp, Imperial Coll, Fac Med, Div Neurosci & Mental Hlth,Dept Cellular & Mol Ne, London, England
基金
英国惠康基金;
关键词
focal ischaemia; heat shock protein; MRI; apparent diffusion coefficient;
D O I
10.1016/j.expneurol.2005.05.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Heat shock proteins (HSPs) have been reported to increase cell survival in response to a wide range of cellular challenges. However, the role of HSP70 overexpression is still a matter of debate, with some reports showing protection and others not. In order to resolve these discrepancies and further investigate the action of these proteins in vivo, transgenic mice overexpressing HSP70 have been compared to wildtype mice in a middle cerebral artery occlusion model of permanent cerebral ischaemia. Previously, the effect of HSP70 was assessed histologically postmortem. In this report, magnetic resonance imaging (MRI) was used to assess the mice in vivo after the onset of stroke. The lesion volume, as measured at 24 h using T(2)-Weighted MRI, was significantly smaller in HSP70 transgenic mice compared with wildtype mice. The smaller lesion size in HSP70 transgenic mice could not be attributed to differences in vascular anatomy or in cerebral blood flow during occlusion. Additionally, the apparent diffusion coefficient showed different spatial and temporal patterns between the groups, suggesting that the damage within the lesion may be less severe for HSP70 transgenic mice. Thus, we conclude that overexpression of HSP70 reduces the overall lesion size and may also limit the tissue damage within the lesion. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:257 / 266
页数:10
相关论文
共 42 条
[1]   The neuroprotective effects of heat shock protein 27 overexpression in transgenic animals against kainate-induced seizures and hippocampal cell death [J].
Akbar, MT ;
Lundberg, AMC ;
Liu, K ;
Vidyadaran, S ;
Wells, KE ;
Dolatshad, H ;
Wynn, S ;
Wells, DJ ;
Latchman, DS ;
de Belleroche, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (22) :19956-19965
[2]   Heat shock protein 27 shows a distinctive widespread spatial and temporal pattern of induction in CNS glial and neuronal cells compared to heat shock protein 70 and caspase 3 following kainate administration [J].
Akbar, MT ;
Wells, DJ ;
Latchman, DS ;
de Belleroche, J .
MOLECULAR BRAIN RESEARCH, 2001, 93 (02) :148-163
[3]   Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow [J].
Alsop, DC ;
Detre, JA .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1996, 16 (06) :1236-1249
[4]   CONSTITUTIVE EXPRESSION OF HEAT-SHOCK PROTEIN-70 IN MAMMALIAN-CELLS CONFERS THERMORESISTANCE [J].
ANGELIDIS, CE ;
LAZARIDIS, I ;
PAGOULATOS, GN .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1991, 199 (01) :35-39
[5]   Overexpression of hsp70i facilitates reactivation of intracellular proteins in neurones and protects them from denaturing stress [J].
Beaucamp, N ;
Harding, TC ;
Geddes, BJ ;
Williams, J ;
Uney, JB .
FEBS LETTERS, 1998, 441 (02) :215-219
[6]   Stress management - heat shock protein-70 and the regulation of apoptosis [J].
Beere, HM ;
Green, DR .
TRENDS IN CELL BIOLOGY, 2001, 11 (01) :6-10
[7]   DIFFUSION-WEIGHTED IMAGING STUDIES OF CEREBRAL-ISCHEMIA IN GERBILS - POTENTIAL RELEVANCE TO ENERGY FAILURE [J].
BUSZA, AL ;
ALLEN, KL ;
KING, MD ;
VANBRUGGEN, N ;
WILLIAMS, SR ;
GADIAN, DG .
STROKE, 1992, 23 (11) :1602-1612
[8]   Measuring cerebral blood flow using magnetic resonance imaging techniques [J].
Calamante, F ;
Thomas, DL ;
Pell, GS ;
Wiersma, J ;
Turner, R .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1999, 19 (07) :701-735
[9]   Severe ADC decreases do not predict irreversible tissue damage in humans [J].
Fiehler, J ;
Foth, M ;
Kucinski, T ;
Knab, R ;
von Bezold, M ;
Weiller, C ;
Zeumer, H ;
Röther, J .
STROKE, 2002, 33 (01) :79-86
[10]   Role of Hsp70 in regulation of stress-kinase JNK: implications in apoptosis and aging [J].
Gabai, VL ;
Meriin, AB ;
Yaglom, JA ;
Volloch, VZ ;
Sherman, MY .
FEBS LETTERS, 1998, 438 (1-2) :1-4