Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse

被引:109
作者
Sheng, HX
Laskowitz, DT
Mackensen, GB
Kudo, M
Pearlstein, RD
Warner, DS
机构
[1] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Med Neurol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[4] Tech Univ Munich, Klinikum Rechts Isar, Dept Anesthesiol, D-8000 Munich, Germany
[5] Yamagata Univ, Dept Anesthesiol & Resuscitat, Yamagata, Japan
关键词
apolipoproteins; cerebral blood flow; ischemia; histology; mice;
D O I
10.1161/01.STR.30.5.1118
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult. Methods-ApoE deficient (n = 16) and wild type (n = 17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by C-14-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia. Results-The percentage of dead hippocampal CA1 neurons (mean+/-SD) was greater in the apoE-deficient group (apoE deficient = 67+/-30%; wild type = 37+/-33%; P=0.011). A similar pattern was observed in the caudoputamen (P = 0.002) and neocortex (P = 0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. Conclusions-ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia.
引用
收藏
页码:1118 / 1123
页数:6
相关论文
共 46 条
[1]   APOE GENOTYPE AND SURVIVAL FROM INTRACEREBRAL HEMORRHAGE [J].
ALBERTS, MJ ;
GRAFFAGNINO, C ;
MCCLENNY, C ;
DELONG, D ;
STRITTMATTER, W ;
SAUNDERS, AM ;
ROSES, AD .
LANCET, 1995, 346 (8974) :575-575
[2]   Regional CBF in apolipoprotein E-deficient and wild type mice during focal cerebral ischemia [J].
Bart, RD ;
Sheng, HX ;
Laskowitz, DT ;
Pearlstein, RD ;
Warner, DS .
NEUROREPORT, 1998, 9 (11) :2615-2620
[3]   The rat extracellular superoxide dismutase dimer is converted to a tetramer by the exchange of a single amino acid [J].
Carlsson, LM ;
Marklund, SL ;
Edlund, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (11) :5219-5222
[4]   Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion [J].
Chan, PH ;
Kawase, M ;
Murakami, K ;
Chen, SF ;
Li, YB ;
Calagui, B ;
Reola, L ;
Carlson, E ;
Epstein, CJ .
JOURNAL OF NEUROSCIENCE, 1998, 18 (20) :8292-8299
[5]   Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug - Evidence for chronic encephalopathic processes following ischemia [J].
Coimbra, C ;
Drake, M ;
BorisMoller, F ;
Wieloch, T .
STROKE, 1996, 27 (09) :1578-1585
[6]   MOTOR-PERFORMANCE IN RATS EXPOSED TO SEVERE FOREBRAIN ISCHEMIA - EFFECT OF FASTING AND 1,3-BUTANEDIOL [J].
COMBS, DJ ;
DALECY, LG .
STROKE, 1987, 18 (02) :503-511
[7]   Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57Black/6 mice [J].
Fujii, M ;
Hara, H ;
Meng, W ;
Vonsattel, JP ;
Huang, ZH ;
Moskowitz, MA .
STROKE, 1997, 28 (09) :1805-1810
[8]   TYPE-III HYPERLIPOPROTEINEMIA ASSOCIATED WITH APOLIPOPROTEIN-E DEFICIENCY [J].
GHISELLI, G ;
SCHAEFER, EJ ;
GASCON, P ;
BREWER, HB .
SCIENCE, 1981, 214 (4526) :1239-1241
[9]   MEMORY DEFICITS AND CHOLINERGIC IMPAIRMENTS IN APOLIPOPROTEIN E-DEFICIENT MICE [J].
GORDON, I ;
GRAUER, E ;
GENIS, I ;
SEHAYEK, E ;
MICHAELSON, DM .
NEUROSCIENCE LETTERS, 1995, 199 (01) :1-4
[10]   INCREASED AMYLOID PROTEIN-PRECURSOR AND APOLIPOPROTEIN-E IMMUNOREACTIVITY IN THE SELECTIVELY VULNERABLE HIPPOCAMPUS FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN GERBILS [J].
HALL, ED ;
OOSTVEEN, JA ;
DUNN, E ;
CARTER, DB .
EXPERIMENTAL NEUROLOGY, 1995, 135 (01) :17-27