Memantine and Q-VD-OPh Treatments in Experimental Spinal Cord Injury: Combined Inhibition of Necrosis and Apoptosis

被引:7
作者
Aydoseli, Aydin [1 ]
Can, Halil [2 ]
Aras, Yavuz [1 ]
Sabanci, Pulat Akin [1 ]
Akcakaya, Mehmet Osman [3 ]
Unal, Omer Faruk [1 ]
机构
[1] Istanbul Univ, Istanbul Sch Med, Dept Neurosurg, Istanbul, Turkey
[2] Med Hosp Asia, Dept Neurosurg, Istanbul, Turkey
[3] Taksim Training & Res Hosp, Dept Neurosurg, Istanbul, Turkey
关键词
Spinal cord injury; Q-VD-OPh; Apoptosis; Memantine; Necrosis; Neuroprotection; FOCAL CEREBRAL-ISCHEMIA; MAGNESIUM-SULFATE; RECEPTOR ANTAGONIST; CASPASE INHIBITOR; FUNCTIONAL-ROLE; AMINO-ACIDS; RAT; RECOVERY; DEATH; IMPROVES;
D O I
10.5137/1019-5149.JTN.12999-14.1
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
AIM: To evaluate the effects of NMDA receptor antagonist memantine and pancaspase inhibitor Q-VD-Oph in combination or alone in experimental spinal cord injury. MATERIAL and METHODS: 45 male Sprague-Dawley rats were divided into five groups. Spinal cord injury was created with the clip compression technique. The drugs were administered either alone of in combination to the subjects according to their groups. Motor function was assessed with Tarlov's motor grading scale and the inclined plane technique. The subjects were sacrificed at the fifth postoperative day. Histopathological examination was done with the use of hematoxylin eosin and TUNEL staining. RESULTS: The results for TUNEL staining and apoptotic cell counts revealed statistically significant differences in Q-VD-Oph and combined treatment groups. Tarlov motor grading scale and inclined plane test results were also found significantly better in these two groups. CONCLUSION: Combined use of memantine and Q-VD-OPh provides better histological and clinical results. The combined inhibition of the two major pathways, necrosis and apoptosis, needs to be further assessed with in-vivo or in-vitro studies.
引用
收藏
页码:783 / 789
页数:7
相关论文
共 45 条
[1]
Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties [J].
Caserta, TM ;
Smith, AN ;
Gultice, AD ;
Reedy, MA ;
Brown, TL .
APOPTOSIS, 2003, 8 (04) :345-352
[2]
CHOI DW, 1987, J NEUROSCI, V7, P357
[3]
Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury [J].
Çolak, A ;
Karaoglan, A ;
Barut, S ;
Köktürk, S ;
Akyildiz, AI ;
Tasyürekli, M .
JOURNAL OF NEUROSURGERY-SPINE, 2005, 2 (03) :327-334
[4]
Çolak A, 2009, NEUROCIRUGIA, V20, P533
[5]
Apoptosis [J].
Cummings, MC ;
Winterford, CM ;
Walker, NI .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1997, 21 (01) :88-101
[6]
MAGNESIUM-DEFICIENCY INVITRO ENHANCES FREE RADICAL-INDUCED INTRACELLULAR OXIDATION AND CYTOTOXICITY IN ENDOTHELIAL-CELLS [J].
DICKENS, BF ;
WEGLICKI, WB ;
LI, YS ;
MAK, IT .
FEBS LETTERS, 1992, 311 (03) :187-191
[7]
Acute spinal cord injury, part II: Contemporary pharmacotherapy [J].
Dumont, RJ ;
Verma, S ;
Okonkwo, DO ;
Hurlbert, J ;
Boulos, PT ;
Ellegala, DB ;
Dumont, AS .
CLINICAL NEUROPHARMACOLOGY, 2001, 24 (05) :265-279
[8]
Memantine for prevention of spinal cord injury in a rabbit model [J].
Ehrlich, M ;
Knolle, E ;
Ciovica, R ;
Böck, P ;
Turkof, E ;
Grabenwöger, M ;
Cartes-Zumelzu, F ;
Kocher, A ;
Pockberger, H ;
Fang, WC ;
Wolner, E ;
Havel, M .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 1999, 117 (02) :285-290
[9]
Geranylgeranylacetone limits secondary injury, neuronal death, and progressive necrosis and cavitation after spinal cord injury [J].
Fujiki, M ;
Furukawa, Y ;
Kobayashi, H ;
Abe, T ;
Ishii, K ;
Uchida, S ;
Kamida, T .
BRAIN RESEARCH, 2005, 1053 (1-2) :175-184
[10]
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