Glucocorticoids Aggravate Retrograde Memory Deficiency Associated with Traumatic Brain Injury in Rats

被引:43
作者
Chen, Xin [1 ]
Zhang, Ke-Li [3 ]
Yang, Shu-Yuan [1 ]
Dong, Jing-Fei [2 ]
Zhang, Jian-Ning [1 ]
机构
[1] Tianjin Med Univ, Gen Hosp, Tianjin Neurol Inst, Dept Neurosurg, Tianjin 300052, Peoples R China
[2] Baylor Coll Med, Dept Med, Thrombosis Res Sect, Houston, TX 77030 USA
[3] Tianjin Baodi Hosp, Dept Neurosurg, Tianjin, Peoples R China
关键词
apoptosis; glucocorticoid; retrograde memory deficiency; traumatic brain injury; APOPTOTIC CELL-DEATH; HEAD-INJURY; BASOLATERAL AMYGDALA; DNA FRAGMENTATION; SPATIAL MEMORY; WATER-MAZE; RETRIEVAL; HIPPOCAMPUS; ISCHEMIA; IMPAIRMENT;
D O I
10.1089/neu.2007.0504
中图分类号
R4 [临床医学];
学科分类号
100218 [急诊医学];
摘要
Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48 h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI.
引用
收藏
页码:253 / 260
页数:8
相关论文
共 31 条
[1]
Allen T. C., 1992, ARMED FORCES I PATHO, P53
[2]
Brain Trauma Foundation, 2007, J Neurotrauma, V24 Suppl 1, pS91
[3]
Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].
Crowe, MJ ;
Bresnahan, JC ;
Shuman, SL ;
Masters, JN ;
Beattie, MS .
NATURE MEDICINE, 1997, 3 (01) :73-76
[4]
Stress and glucocorticoids impair retrieval of long-term spatial memory [J].
de Quervain, DJF ;
Roozendaal, B ;
McGaugh, JL .
NATURE, 1998, 394 (6695) :787-790
[5]
EFFECT OF HIGH-DOSE DEXAMETHASONE ON OUTCOME FROM SEVERE HEAD-INJURY [J].
DEARDEN, NM ;
GIBSON, JS ;
MCDOWALL, DG ;
GIBSON, RM ;
CAMERON, MM .
JOURNAL OF NEUROSURGERY, 1986, 64 (01) :81-88
[6]
EARLY MICROVASCULAR AND NEURONAL CONSEQUENCES OF TRAUMATIC BRAIN INJURY - A LIGHT AND ELECTRON-MICROSCOPIC STUDY IN RATS [J].
DIETRICH, WD ;
ALONSO, O ;
HALLEY, M .
JOURNAL OF NEUROTRAUMA, 1994, 11 (03) :289-301
[7]
Very delayed infarction after mild focal cerebral ischemia: A role for apoptosis? [J].
Du, C ;
Hu, R ;
Csernansky, CA ;
Hsu, CY ;
Choi, DW .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1996, 16 (02) :195-201
[8]
IDENTIFICATION OF PROGRAMMED CELL-DEATH INSITU VIA SPECIFIC LABELING OF NUCLEAR-DNA FRAGMENTATION [J].
GAVRIELI, Y ;
SHERMAN, Y ;
BENSASSON, SA .
JOURNAL OF CELL BIOLOGY, 1992, 119 (03) :493-501
[9]
Laurer H.L., 2002, ENCY HUMAN BRAIN, P93
[10]
The acute effects of corticosteroids on cognition: Integration of animal and human model studies [J].
Lupien, SJ ;
McEwen, BS .
BRAIN RESEARCH REVIEWS, 1997, 24 (01) :1-27