臺灣博碩士論文加值系統

本研究分為兩個主要的部份，第一部份是有關於脊髓缺血再灌流傷害後傷害之嚴重程度與細胞死亡機制之間的關係以及神經保護之探討。胸腰椎脊髓之血液供應主要是來自於胸腹主動脈。因脊髓缺血而導致下肢癱瘓是胸腹主動脈手術的嚴重併發症。先前的研究指出中樞神經系統之缺血再灌流傷害會引起兩種不同形態之細胞死亡，即細胞壞死和細胞凋亡。也有研究暗示傷害之嚴重程度可能會影響到細胞死亡之機制。在第一部份的研究中，我們將大白鼠之胸主動脈阻塞造成脊髓之缺血再灌流傷害，並且藉由是否同時抽血引發缺血性低血壓，建立了一個可以控制傷害嚴重程度之脊髓缺血再灌流的動物模型。術中頸動脈血壓及脊髓血流量監測顯示，胸主動脈阻塞在正常血壓組與低血壓組之大白鼠都會造成大幅的頸動脈血壓上升及脊髓血流量降低。然而，低血壓組在胸主動脈阻塞期間之脊髓血流量降得更低，再灌流後脊髓血流量回升之速度較緩慢，而且後肢之運動功能受損程度也較為嚴重。腰椎段脊髓表現出嚴重之梗塞、明顯之細胞壞死、及缺乏細胞凋亡之現象。相反地，正常血壓組在受到相同時間之脊髓缺血再灌流傷害後，脊髓組織傷害及後肢之運動功能受損程度都較為輕微，但是細胞凋亡之現象及caspase-3之活性卻較為旺盛及持續。而脊髓前角中之運動神經細胞較少發生細胞凋亡之現象可能是正常血壓組神經功能受損較輕微的主要原因。我們的研究發現缺血再灌流傷害之嚴重程度對受傷脊髓之病理變化及細胞死亡之機制有相當程度之影響。我們的研究結果也暗示，傷害的嚴重程度及傷害後之時間點是在從事治療時必須要考慮之重要因素。
由於細胞壞死及細胞凋亡是脊髓缺血再灌流傷害後會引發細胞死亡之兩種主要機制，我們因而假設將NMDA接受器抑制劑MK-801及蛋白質合成抑制劑cycloheximide併用可能在脊髓缺血再灌流傷害之治療上有加成之效果。在第二部份的研究中，我們仍然將大白鼠之胸主動脈阻塞並同時減少血液容積量以造成脊髓之缺血，將抽出之血液注回以引起再灌流傷害。然後我們將大白鼠分為四個實驗組，分別接受載體、MK-801、cycloheximide、或MK-801與cycloheximide合併之治療。研究結果顯示，MK-801組及合併治療組後肢運動功能之恢復優於控制組及cycloheximide組。三個治療組在第七天之神經細胞存活率顯著優於控制組。與控制組相比，cycloheximide組與合併治療組之脊髓切面上之凋亡細胞總數有顯著之減少。而MK-801組則維持不變。這些結果顯示同時將與NMDA接受器有關之細胞毒性及與caspase 有關之細胞凋亡抑制可能在脊髓缺血再灌流傷害之治療上有相當之潛力。
Mitogen-activated protein kinases (MAPK) 包括了c-Jun N-terminal kinases (JNK)、 p38及extracellular signal-regulated kinases (ERK)，在細胞面臨壓力時訊息的傳遞和細胞反應的整合中扮演了重要的角色。雖然一般的看法認為JNK和 p38與細胞的死亡及退化有關，而ERK則是與細胞的分裂及存活有關，爭論卻依然存在。尤其是關於ERK訊息傳遞路徑在中樞神經系統之缺血再灌流傷害中所扮演之角色，文獻上有完全相反的報告，因此極待釐清。基於這樣的爭議，在第三部份的實驗中，我們檢測脊髓缺血再灌流傷害後ERK1/2之變化，以及抑制使ERK1/2磷酸化之分子MEK之效果。實驗結果顯示，缺血再灌流傷害在脊髓內引發立即性的ERK1/2磷酸化，而此磷酸化可被MEK之抑制劑U0126所抑制。
控制組的神經缺損恢復較差、脊髓組織破壞較嚴重、細胞凋亡之現象較明顯、神經細胞存活率也較低。相反的，U0126治療組後肢運動功能之進步較明顯、脊髓組織破壞較輕微、細胞凋亡之現象較少、神經細胞存活率也較高。此外，U0126的給予也顯著提高了nuclear factor-κB (NF-κB)之活化與cellular inhibitor of apoptosis protein 2 (c-IAP2)之表現。這些發現暗示著抑制ERK1/2所造成的神經保護效果可能是經由NF-κB-c-IAP2這條路徑所致。MEK-ERK訊息傳遞路徑過度活化在我們的實驗模型中所扮演之角色似乎是弊多於利。能夠將此一路徑阻斷之策略或許在脊髓缺血再灌流傷害的治療上具有相當之潛力。
本研究之第二部份是有關於背側脊椎手術與脊柱側肌肉傷害之關係，與避免此類傷害方法之探討。在執行背側脊椎手術時經常須要將脊柱側肌肉剝離並用力撐開，此舉可能會對此肌肉造成結構及功能上之傷害。術後脊柱側肌肉中立即發生之病理變化不僅會造成嚴重的疼痛，也會延遲病患下床活動的時間。長期的不良結果還包括了慢性背痛及背部肌肉無力。諷刺的是，雖然脊柱側肌肉的傷害是背側脊椎手術常見的併發症，它卻是如此地被忽略。文獻中有限的報告指出外科手術對脊柱側肌肉之傷害包括了物理性與缺血性之傷害。我們因而假設手術中剝離與撐開的動作會對脊柱側肌肉造成氧化壓力。同時，我們也假設此氧化壓力會在受創肌肉中引發某種自我保護之機制。此研究之第一部份涉及一人體試驗，目的在於評估手術中撐開下人體脊柱側肌肉內氧化壓力所扮演之角色與其和由heat shock protein (HSP70)主導的壓力反應機制之間的關係。
試驗對象是一群因患有腰椎滑脫必須接受背側腰椎融合、固定及減壓手術之病患。手術中在脊柱側肌肉撐開前、撐開中及撐開後固定時間點作多裂肌之切片。我們分別檢測肌肉檢體中之HSP70和malondialdehyde (MDA)的量。結果顯示手術中的肌肉撐開會使多裂肌細胞中之HSP70和malondialdehyde (MDA)的量顯著上升。肌肉中HSP70的表現在撐開後約1.5小時後開始下降，而MDA的量卻一直到肌肉撐開器放鬆後都還維持上升之狀態。病理組織學及免疫組織染色之證據顯示撐開晚期HSP70合成之減少是肌肉嚴重受損之結果。
這些實驗結果在細胞及分子層面指出了手術中將脊柱側肌肉撐開對該肌肉之害處，以及氧化壓力之重要性。這些結果也暗示能夠降低脊柱側肌肉中氧化壓力之措施或許可以減少手術對脊柱側肌肉之傷害。
基於上述之發現，也由於文獻中指出發炎反應是發生於受到手術傷害之脊柱側肌肉中主要的病理變化，我們於是進一步檢測兩個與發炎反應有關之重要介質，即cyclooxygenase (COX)-2 和nuclear factor (NF)-κB，在手術所引起之脊柱側肌肉傷害中所扮演之角色。
首先我們建立了一個摹擬人體背側脊椎手術之大白鼠模型。控制組大白鼠先接受背側脊柱側肌肉之剝離及撐開。脊柱側肌肉撐開前、撐開中及撐開後固定時間點作肌肉之切片。經由對這些肌肉檢體之分析，我們分別檢測NF-κB之活化和COX-2之表現的時間順序。發炎反應之嚴重程度則由組織中病理變化及myeloperoxidase (MPO)的量來評估。另一組大白鼠接受同樣之手術步驟，但給予pyrrolidine dithiolcarbamate (PDTC)以抑制NF-κB之活化。實驗結果顯示在控制組中，肌肉撐開會使脊柱側肌肉細胞中之NF-κB/DNA之結合能力在撐開早期就上升，並在整個撐開過程中持續。而COX-2之表現要到術後一天時才能檢測得到，並且在第三天時達到高峰。COX-2表現之時間與病理切片及MPO量所透露出的發炎嚴重度相當一致。術後七天時肌肉切片顯示廣泛的肌肉細胞喪失及纖維組織增生的現象。而術前給予PDTC有效地抑制NF-κB之活化，並大幅降低了COX-2的表現和肌肉中的發炎。肌肉組織纖維化的情形也顯著地減少。
這些實驗結果顯示由NF-κB調控之COX-2表現及發炎反應在手術所引起之脊柱側肌肉之傷害機制中扮演了重要之角色。能夠抑制NF-κB活化之治療策略或許可應用於保護脊柱側肌肉免於此類傷害。

Abstract
The first part of this research was focused on the relationship between injury severity and cell death mechanisms after spinal cord ischemia-reperfusion injury. The major blood supply to the thoracolumbar spinal cord comes from the segmental arteries originating from the thoracoabdominal aorta. Paraplegia cause by spinal cord ischemia is a devastating complication of thoracoabdominal aortic surgery. Previous studies indicated that ischemia-reperfusion injury of the central nervous system causes two distinct types of cell death, necrosis and apoptosis. It was also implicated that the intensity of injury can somehow affect the cell death mechanisms. In the first series of our experiments, by occluding the descending thoracic aorta with or without simultaneously inducing hypovolemic hypotension in rats, we established a model of experimental spinal cord ischemia-reperfusion (SCIR) in which the injury severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups. However, the HT group demonstrated significantly lower SCBF during aortic occlusion, and much slower elevation of SCBF after reperfusion, and extremely poor neurological performance. Spinal cord lesions were characterized by infarction associated with extensive necrotic cell death, but little apoptosis and caspase-3 activity. In contrast, in the NT group, SCIR resulted in minor tissue destruction associated with persistently abundant apoptosis, augmented caspase-3 activity, and favorable functional outcome. The relative sparing of motoneurons in the ventral horns from apoptosis might have accounted for the minor functional impairment in the NT group. The severity of ischemia-reperfusion (I/R) injury was found to have substantial impact on the histopathological changes and cell death mechanisms, which correlated with neurological performance. These findings implicate that injury severity and duration after injury are two critical factors to be considered in therapeutic intervention.
Based on the knowledge that bPrevious studies have implicated both excitotoxicity and apoptosis are involved in the pathogenesis of SCIR injury, we proposedtested the possibility that the N-methyl-D-aspartate (NMDA) receptor antagonist (dizocilpine maleate: (MK801) and the protein synthesis inhibitor (cycloheximide) would produce a synergic effect in the treatment of SCIR injury. In the second series of experiments, I/R iSpinal cord ischemia-reperfusion injury was induced by a thoracic aortic occlusion and blood volume reduction, followed by reperfusion and volume restoration. ischemia-reperfusion Rats were treated with vehicle, MK801, cycloheximide, or combination of MK801 and cycloheximide in combination. The MK801 and combined therapy group got a better recovery of hHind limb motor function recovery was better in the MK801 and combined-therapy groups than in the control and cycloheximide groups. On the 7th day after ischemia-reperfusion injury, all three treated groups showed significantly higher neuronal survival rates (NSR) than that of the control group. Among the three treated groups, the combined-treatment group showed the highest NSR. In addition, the Ttherapeutic effect of the combined-treatment group (27.4% increase of NSR) iwas better than the anticipated by the addition of MK801 and cycloheximide based on NSR data group. The number of apoptotic cells of was significantly reduced in the cycloheximide group and the combined-treatment group, as compared to that of the control group. It was unchanged in the MK-801 group. These results suggest that combined treatments directed at blocking both NMDA receptor-mediated excitotoxic necrosis and caspase-mediated apoptosis might have synergic therapeutic potential in reducing SCIR injury.
Mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinases (JNK), p38, and extracellular signal-regulated kinases (ERK), play important roles in the transduction of stressful signals and the integration of cellular responses. Although it has been generally held that the JNK and p38 pathways are related to cell death and degeneration, while the ERK pathway, cell proliferation and survival, controversy still exists. The roles of the ERK pathway in I/R injury of the CNS, in particular, remain to be clarified, because contradictory data have been reported by different investigators. Given this controversy, in the third series of experiments, we examined in injured spinal cords the temporal and spatial profiles of ERK1/2 activation following SCIR, and the effects of inhibiting the kinase that phosphorylates ERK1/2, MEK. The results showed that I/R injury induced an immediate phosphorylation of ERK1/2 in the spinal cord, which was alleviated by a MEK inhibitor, U0126. The control group was characterized by poorer neurological outcome, more severe tissue destruction, pronounced apoptosis, and lower neuronal survival. In contrast, the U0126-treated group demonstrated more apparent improvement of hind limb motor function, less tissue destruction, lack of apoptosis, and higher neuronal survival. In addition, administration of U0126 also significantly increased the activation of nuclear factor-κB (NF-κB) and the expression of cellular inhibitor of apoptosis protein 2 (c-IAP2). These findings implicate that the mechanisms underlying the neuroprotection afforded by ERK1/2 inhibition may be through the NF-κB-c-IAP2 axis. The activation of the MEK-ERK signaling pathway appeared to be harmful in SCIR injury. Strategies aimed at blocking this pathway may bear potential therapeutic benefits in the treatment of SCIR injury.
The second part of the research was focused on the pathophysiology of surgery-associated paraspinal muscle injury and measures to protect surgically violated paraspinal muscles. The wide dissection and forceful retraction of paraspinal muscles which are often required for posterior spinal sugery may severely jeopardize the muscles structurally and functionally. Immediate posteoperative pathological changes in the surgically violated paraspinal muscles may cause severe pain and a delay of patient ambulation. Long-term sequelae of surgical injury of paraspinal muscles include chronic back pain and impaired back muscle strength. Ironically, being a common complication of posterior spinal surgery, paraspinal muscle injury is so often neglected. Limited previous data indicate that the underlying pathophysiology of muscle damage involve both mechanical and ischemic mechanisms. We hypothesized that surgical dissection and retraction may produce oxidative stress within the paraspinal muscles. Meanwhile, we also proposed that the oxidative stress may trigger certain protective mechanisms within the insulted muscles. The first part of our study was a human study conducted to assess the significance of oxidative stress, and the relationship between it and the stress response mediated by heat shock protein 70 (HSP70) induction within paraspinal muscles under intraoperative retraction.
A group of patients with lumbar spondylolisthesis treated with posterolateral lumbar spinal fusion, pedicle fixation and laminectomy were enrolled. Multifidus muscle specimens were harvested intraoperatively before, at designated time points during, and after surgical retraction. Muscle samples were analyzed for HSP70 and malondialdehyde (MDA) levels. Both HSP70 expression and MDA production within multifidus muscle cells were increased significantly by retraction. HSP70 expression then dropped after a peak at 1.5 hr of retraction, whereas MDA levels remained elevated even after release of retractors for reperfusion of the muscles. Histopathological and immunohistochemical evidence indicated that the decline of HSP70 synthesis within muscle cells after prolonged retraction was the result of severe muscle damage.
These results highlighted the noxious impact of intraoperative retraction on human paraspinal muscles, and the significance of oxidative stress at the cellular and molecular levels. It is also implicated that intraoperative maneuvers aimed at reducing the oxidative stress within the paraspinal muscles may help attenuating surgery-associated paraspinal muscle damage.
Given the findings of the first part of our study, and the knowledge that inflammation is a major postoperative pathological finding in surgically injured paraspinal muscles, we proceeded to examine the roles of two important inflammatory mediators, cyclooxygenase (COX)-2 and nuclear factor (NF)-κB, in the pathogenesis of retraction-associated paraspinal muscle injury.
A rat model of paraspinal muscle dissection and retraction that mimicks the conditions in human posterior spinal surgery was established. In the control group, paraspinal muscles were dissected from the spine through a dorsal incision, and then laterally retracted. Paraspinal muscle specimens were harvested before, and at designated time points during and after persistent retraction. The time course of NF-κB activation as well as the expression of COX-2 were examined. Severity of inflammation was evaluated based on histopathology and myeloperoxidase (MPO) activity. NF-κB activation was inhibited by the administration of pyrrolidine dithiolcarbamate (PDTC) in the PDTC-treated group. In the control group, retraction induced an early increase of NF-κB/DNA binding activity in paraspinal muscle cells, which persited throughout the whole course of retraction. COX-2 expression was not detectable until 1 day after surgery, and reached a peak at 3 days. The time course of COX-2 expression correlated with that of inflammatory pathology and MPO activity. Extensive muscle fiber loss and collagen fiber replacement were observed at 7 days after surgery. Pretreatment with PDTC inhibited intraoperative NF-κB activation and greatly downregulated postoperative COX-2 expression and inflammation in the muscles. Fibrosis following inflammation was also significantly abolished by PDTC administration.
These findings indicate that NF-κB-regulated COX-2 expression and inflammation play an important role in the pathogenesis of surgery-associated paraspinal muscle injury. Therapeutic strategies involving NF-κB inhibition may be applicable to the prevention of such injury.

中文摘要 ……………………………………………………………………………..1
Abstract ……………………………………………………………………………….5

Chapter 1 Injury Severity and Cell Death Mechanisms: Effects of Concomitant Hypovolemic Hypotension on Spinal Cord Ischemia-Reperfusion in Rats
1.1 Introduction ……………………………………………………………………..11
1.2 Hypotheses and Research Objectives ……………………………………………15
1.3 Materials and Methods …………………………………………………………..16
1.4 Results …………………………………………………………………………...22
Table 1.1 ……………………………………………………………………………..26
1.5 Discussion ……………………………………………………………………….37
1.6 Conclusion ………………………………………………………………………42

Chapter 2 Inhibition of Phosphorylation of Extracellular Signal-Regulated Kinases (ERK1/ERK2) Provides Neuroprotection after Spinal Cord
2.1 Introduction ………………………………………………………...……………43
2.2 Materials and Methods ………………………………………………...………...47
2.3 Results ……………………………………………………...……………………51
2.4 Discussion …………………………………………...…………………………..64
2.5 Conclusions …………………………………..……………………….…………66

Chapter 3 Oxidative Stress and Heat Shock Protein Response within Human Paraspinal Muscles during Retraction
3.1 Introduction ……………………………………………..……………………… 67
3.2 Materials and Methods ………………………………..…………………………70
3.3 Results ………………………………………………..………………………… 75
Table 3.1 ……………………………………………………………………………..77
3.4 Discussion …………………………………………….…………………………82
3.5 Conclusions ……………………………………..……………………………….84

References …………………………………………………..……………………….87

Chapter 4 Nuclear Factor-κB-Regulated Cyclooxygenase-2 Expression in Surgery-Associated Paraspinal Muscle Injury in Rats
4.1 Introduction ……………………………………………………………………..88
4.2 Materials and Methods ………………………………………………………….91
4.3 Results …………………………………………………………………………...97
4.4 Discussion ……………………………………………………………………...106
4.5 Conclusion ……………………………………………………………………..110

Chapter 5 Directions of Future Research
5.1 On the Autoregulation of Spinal Cord Blood Flow ……………………………111
5.2 On Signal Transduction Pathways …..…………………………………………113
5.3 On Surgery-Associated Paraspinal Muscle Injury ………….………………….114

References ………………………………………………………………………….116

Acknowledgment …………………………………………………………………..135

Publications Related to this Thesis ………………………………………………....136

References
1.Aiwaka R, Komuro I, Yamazaki T, Zou Y, Kudoh S, Takaka M, Shiojima I, Hiroi Y, Yazaki Y. 1997. Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J Clin Invest 100: 1813-1821.
2.Alessandrini A, Namura S, Moskowitz MA, Bonventre JV. 1999. MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proc Natl Acad Sci USA 96: 12866-12869.
3.Backstrom T, Saether OD, Norgren L, Aadahl P, Myhre HO, Understedt U. 2001. Spinal cord metabolism during thoracic aortic cross-clamping in pigs with special reference to the effect of allopurinol. Eur J Vasc Endovasc Surg 22: 410-417.
4.Baeuerle PA, Henkel T. 1994. Function and activation of NF-κB in the immune system. Annu Rev Immunol 12: 141-179.
5.Baldwin AS, Jr. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu Rev Immunol 14: 649-683.
6.Barone FC, Feuerstein GZ. 1999. Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19: 819-834.
7.Barr RK, Bogoyevitch MA. The c-Jun N-terminal protein family of mitogen-activated protein kinases (JNK MAPKs). 2001. Int J Biochem Cell Biol 33: 1047-1063.
8.Becker KJ. 1998. Inflammation and acute stroke. Curr Opin Neurol 11: 45-49.
9.Beckmann RP, Mizzen LA, Welch WJ. 1990. Interaction of HSP 70 with newly synthesized proteins: implications for protein folding and assembly. Science 248: 850-854.
10.Beg AA, Baltimore D. 1996. An essential role for NF-κB in preventing TNF-alpha-induced cell death. Science 274: 782-784.
11.Benavente OR, Barnett HJM. 1995. Spinal cord infarction, in Cater, L. P., Spetzler, R. F. (Eds), Neurovascular Surgery. McGraw-Hill Inc., New York, pp, 1229-1240.
12.Biglioli P, Spirito R, Roberto M, Grillo F, Cannata A, Parolari A, Maggioni M, Coggi G. 2000. The anterior spinal artery: the main arterial supply of the human spinal cord － a preliminary anatomi study. J Thorac Cardiovasc Surg 119: 376-379.
13.Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH. 1996. Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart: P38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res 79: 162-173.
14.Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewka E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD. 1991. ERKs: a family of protein-serine/threonine kinase that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 65: 663-675.
15.Callejas NA, Casado M, Bosca L, Martin-Sanz P. 1999. Requirement of nuclear factor κB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts. J Cell Sci 112: 3147-3155.
16.Carter AB, Hunninghake GW. 2000. A constitutive active MEK → ERK pathway negatively regulates NF-κB-dependent gene expression by modulating TATA-binding protein phosphorylation. J Biol Chem 275: 27858-27864.
17.Chang L, Karin M. 2001. Mammalian MAP kinase signalling cascades. Nature 410: 37-40.
18.Choi DW. 1988. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci 10: 465-469.
19.Chu ZL, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW. 1997. Suppression of tumor necrosis factor-induced cell death by inhibition of apoptosis c-IAP2 is under NF-kappa B control. Proc Natl Acad Sci USA 94: 10057-10062.
20.Crawford ES, Crawford JL, Safi HJ, Coselli JS, Hess KR, Brooks B. 1986. Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patiens. J Vasc Surg 3: 389-404.
21.Creedon DJ, Johnson EM, Lawrence JC. 1996. Mitogen-activated protein kinase-independent pathways mediate the effect of nerve growth factor and cAMP on neuronal survival. J Biol Chem 271: 20713-20718.
22.Crofford LJ. 1997. COX-1 and COX-2 tissue expression: implications and predictions. J Rheumatol 24 (Suppl 49): 15-19.
23.Cryns V, Yuan J. 1998. Proteases to die for. Genes Develop 12: 1551-1570.
24.Currie RW, White FP. 1981. Trauma-induced protein in rat tissue: a physiological role for a “heat shock” protein? Science 214: 72-73.
25.D’Aquisto F, Ialenti A, Di Vaio R, Carnuccio R. 2000. Local administration of transcription factor decoy oligonucleotides to nuclear factor-κB prevents carrageenin-induced inflammation in rat hind paw. Gene Ther 7: 1731-1737.
26.Davis RJ. 1993. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268: 14553-14556.
27.Davis RJ. 2000. Signal transduction by the JNK group of MAP kinases. Cell 103: 239-252.
28.De Haan P, Kalkman CJ, Jacobs MJHM. 2001. Pharmacologic neuroprotection in experimental spinal cord ischemia. J Neurosurg Anesthesiol 13: 3-12.
29.DeMeester SL, Buchman TG, Cobb JP. 2001. The heat shock paradox: does NF-κB determine cell fate? FASEB J 15: 270-274.
30.Deveraux QL, Roy N, Stennicke HR, Arsdale TV, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC. 1997. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388: 300-304.
31.DeWitt DL. 1991. Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochim Biophys Acta 1083: 121-134.
32.Di Chiro G, Fried LC. 1971. Blood flow currents in spinal cord arteries. Neurology 21: 1088-1096.
33.Dickman CA, Fessler RG, MacMillan M, Haid RW. 1992. Transpedicular screw-rod fixation of the lumbar spine: operative technique and outcome in 104 cases. J Neurosurg 77: 860-870.
34.Dirnagl U, Iadecola C, Moskowitz MA. 1999. Patholbiology of ischemic stroke: an integrated view. Trends Neurosci 22: 391-397.
35.Donnahoo KK, Meng X, Ayala A, Cain MP, Harken AH, Meldrum DR. 1999. Early kidney TNF-α expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Am J Physiol 277: R922-929.
36.Eldadah BA, Faden AI. 2000. Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma 17: 811-829.
37.Elder CL, Dahners LE, Weinhold PS. 2001. A cyclooxygenase-2 inhibitor impairs ligament healing in the rat. Am J Sports Med 29: 801-805.
38.Endres M, Namura S, Shimizu-Sasamata M, Waeber C, Zhang L, Gomez-Isla T, Hyman BT, Moskowitz MA. 1998. Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J Cereb Blood Flow Metab 18: 238-247.
39.Esterbauer H, Schaur RJ, Zollner H. 1991. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11: 81-128.
40.Fabbraio MA, Koukoulas I. 2000. HSP72 gene expression progressively increases in human skeletal muscle during prolonged, exhaustive exercise. J Appl Physiol 89: 1055-1060.
41.Feng L, Sun W, Xia Y, Tang WW, Chanmugam P, Soyoola E, Wilson CB, Hwang D. 1993. Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression. Arch Biochem Biophys 307: 361-368.
42.Fiore RS, Bayer VE, Pelech SL, Posada J, Cooper JA, Baraban JM. 1993. p42 mitogen-activated protein kinase in brain: prominent localization in neuronal cell bodies and dendrites. Neuroscience 55: 463-472.
43.Frerichs KU, Feuerstein GZ. 1990. Laser-Doppler flowmetry: a review of its application for measuring cerebral and spinal cord blood flow. Mol Chem Neuropathol 12: 55-70.
44.Friedlander RM, Yuan J. 1998. ICE, neuronal apoptosis and neurodegeneration. Cell Death Diff 5: 823-831.
45.Funakoshi M, Tago K, Sonoda Y, Tominaga S, Kasahara T. 2001. A MEK inhibitor, PD98059 enhances IL-1-induced NF-κB activation by the enhanced and sustained degradation of IκBα. Biochem Biophys Res Commun 283: 248-254.
46.Funk CD. 2001. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294: 1871-1875.
47.Gejo R, Kawaguchi Y, Kondoh T, Tabuchi E, Matsui H, Torii K, Ono T, Kimura T. 2000. Magnetic resonance imaging and histologic evidence of postoperative back muscle injury in rats. Spine 25: 941-946.
48.Gething MJ, Sambrook J. 1992. Protein folding in the cell. Nature 355: 33-45.
49.Ghosh S, May MJ, Kopp EB. 1998. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16: 225-260.
50.Gillardon F, Kiprianova I, Sandkuhler J, Hossmann KA, Spranger M. 1999. Inhibition of caspases prevents cell death of hippocampal CA1 neurons, but not impairment of hippocampal long-term potentiation following global ischemia. Neuroscience 93: 1219-1222.
51.Girotti AW. 1985. Mechnism of lipid peroxidation. Free Radic Biol Med 1: 87-95.
52.Griffiths IR. 1973. Spinal cord blood flow in dogs: the effect of blood pressure. J Neurol Neurosurg Psychiat 36: 914-920.
53.Gute DC, Ishida T, Yarimizu K, Korthuis RJ. 1998. Inflammatory responses to ischemia and reperfusion in skeletal muslce. Mol Cell Biochem 179: 169-187.
54.Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ. 1996. Activation of mitogen-activated protein kinase by H2O2: role in cell survival following oxidant injury. J Biol Chem 271: 4138-4142.
55.Hara H, Friedlander RM, Gagliardini V, Ayata C, Fink K, Huang Z, Shimizu-Sasamata M, Yuan J, Moskowitz MA. 1997. Inhibition of interleukin 1β convertin enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci USA 94: 2007-2012.
56.Hayashi T, Sakurai M, Abe K, Sadahiro M, Tabayashi K, Itoyama Y. 1998. Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia. Stroke 29: 1007-1013.
57.Hayashi T, Sakai K, Sasaki C, Zhang WR, Warita H, Abe K. 2000. c-Jun N-terminal kinase (JNK) and JNK interacting protein response in rat brain after transient middle cerebral artery occlusion. Neurosci Lett 284: 195-199.
58.Henkart PA. 1996. ICE family proteases: mediators of all apoptotic cell death? Immunity 4: 195-201.
59.Hightower LE. 1991. Heat shock, stress proteins, chaperones, and proteotoxicity. Cell 66: 191-197.
60.Himi T, Ishizaki Y, Murota SI. 1998. A caspase inhibitor blocks ischemia-induced delayed neuronal death in gerbil. Eur J Neurosci 10: 777-781.
61.Hisahara S, Shoji S, Okano H, Miura M. 1997. ICE/CED-3 family executes oligodendrocyte apoptosis by tumor necrosis factor. J Neurochem 69: 10-20.
62.Hollier LH, Symmonds JB, Pairolero PC, Cherry KJ, Hallet JW, Gloviczki P. 1988. Thoracoabdominal aortic aneurysm repair. Analysis of postoperative morbidity. Arch Surg 123: 871-875.
63.Hong SY, Yoon WH, Park JH, Kang SG, Ahn JH, Lee TH. 2000. Involvement of two NF-kappa B binding elements in tumor necrosis factor alpha-, CD40-, and epstein-barr virus latent membrane protein 1-mediated induction of the cellular inhibitor of apoptosis protein 2 gene. J Biol Chem 275: 18022-18028.
64.Hreniuk D, Garay M, Gaarde W, Monia BP, McKay RA, Cioffi CL. 2001. Inhibition of c-Jun N-terminal kinase 1, but not c-Jun N-terminal kinase 2, suppresses apoptosis induced by ischemia/reoxygenation in rat cardiac myocytes. Mol Pharmacol 59: 867-874.
65.Jackson RK. 1971. The long-term effects of wide laminectomy for lumbar disc excision. J Bone Joint Surg [Br] 53: 609-616.
66.Jackson MJ. 1999. Symposium on ‘metabolic aspects of human nutrition at rest and during physical stress: recent methodological and technical developments’. Session 7: methods to assess free radical and antioxidant activity in man. Proceedings of the Nutrition Society 58: 1001-1006.
67.Janero DR. 1990. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9: 515-540.
68.Johnson EW, Burkhart JA, Earl WC. 1972. Electromyography in postlaminectomy patients. Arch Phys Med Rehabil 53: 407-409.
69.Kanellopoulos GK, Kato H, Wu Y, Dougenis D, Mackey M, Hsu CY, Kouchoukos NT. 1997. Neuronal cell death in the ischemic spinal cord: the effect of methylprednisolone. Ann Thorac Surg 64: 1279-1286.
70.Kato H, Kanellopoulos GK, Matsuo S, Wu Y, Jacquin MF, Hsu CY, Kouchoukos NT, Choi DW. 1997a. Neuronal apoptosis and necrosis following spinal cord ischemia in the rat. Exp Neurol 148: 464-474.
71.Katz NM, Blackstone EH, Kirklin JW, Karp RB. 1981. Incremental risk factors for spinal cord injury following operation for acute traumatic aortic transection. J Thorac Cardiovasc Surg 81: 669-674.
72.Kawaguchi Y, Matsui H, Tsuji H. 1994a. Back muscle injury after posterior lumbar spine surgery. Part 1: histologic and histochemical analyses in rats. Spine 19: 2590-2597.
73.Kawaguchi Y, Matsui H, Tsuji H. 1994b. Back muscle injury after posterior lumbar spine surgery, Part 2: Histological and histochemical analysis in humans. Spine 19: 2598-2602.
74.Kawaguchi Y, Matsui H, Tsuji H. 1996a. Back muscle injury after posterior lumbar spine surgery. A histologic and enzymatic analysis. Spine 21: 941-944.
75.Kawaguchi Y, Yabuki S, Styf J, Olmarker K, Rydevik B, Matsui H, Tsuji H. 1996b. Back muscle injury after posterior lumbar spine surgery. Topographic evaluation of intramuscular pressure and blood flow in the porcine back muscle during surgery. Spine 21: 2683-2688.
76.Kawaguchi Y, Matsui H, Tsuji H. 1997. Changes in serum creatine phosphokinase MM isoenzyme after lumbar spine surgery. Spine 22: 1018-1023.
77.Keane RW, Srinivasan A, Foster LM, Testa MP, Ord T, Nonner D, Wang HG, Reed JC, Bredesen DE, Kayalar C. 1997. Activation of CPP32 during apoptosis of neurons and astrocytes. J Neurosci Res 48: 168-180.
78.Kerr JFR, Wyllie AH, Currie AR. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 25: 239-245.
79.Kim GM, Xu J, Song SK, Yan P, Ku G, Xu XM, Hsu CY. 2001. Tumor necrosis factor recptor deletion reduces nuclear factor-κB activation, cellular inhibitor of apoptosis protein 2 expression, and functional recovery after traumatic spinal cord injury. J Neurosci 21: 6617-6625.
80.Kramer M, Katzmaier P, Eisele R, Ebert V, Kinzl L, Hartwig E. 2001. Surface electromyography-verified muscular damage associated with the open dorsal approach of the lumbar spine. Eur Spine J 10: 414-420.
81.Kumar S, Lavin MF. 1996. The ICE family of cysteine proteases as effectors of cell death. Cell Death Diff 3: 255-267.
82.Kurino M, Fukunaga K, Ushio Y, Miyamoto E. 1995. Activation of mitogen-activated protein kinase in cultured rat hippocampal neurons by stimulation of glutamate receptors. J Neurochem 65: 1282-1289.
83.Kyriakis JM, Avruch J. 1996. Protein kinase cascades activated by stress and inflammatory cytokines. Bioassays 18: 567-577.
84.Lassonen EM. 1984. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely rediating lumbar back pain. Neuroradiology 26: 9-13.
85.Lawrence T, Gilroy DW, Colville-Nash PR, Willoughby DA. 2001. Possible new role for NF-κB in the resolution of inflammation. Nat Med 7: 1291-1297.
86.Lee JM, Zipfel GJ, Choi DW. 1999. The changing landscape of ischemic brain injury mechanisms. Nature 399: A7-A14.
87.Levinson W, Oppermann H, Jackson J. 1980. Transition series metals and sulfhydryl reagents induce the synthesis of four proteins in eukaryotic cells. Biochem Biophys Acta 606: 170-180.
88.Lewen A, Matz P, Chan PH. 2000. Free radical pathway in CNS injury. J Neurotrauma 17: 871-890.
89.Lewis WH, eds. 2000. Gray’s Anatomy of the Human Body. Philadelphia: Lea and Febiger, 1918; Bartleby.com.
90.Li GC. 1983. Induction of thermotolerance and enhanced heat shock protein synthesis in Chinese hamster fibroblasts by sodium arsenite and by ethanol. J Cell Physiol 115: 116-122.
91.Li M, Ona VO, Chen M, Kaul M, Tenneti L, Zhang X, Stieg PE, Lipton SA, Friedlander RM. 2000. Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience 99: 333-342.
92.Lille ST, Lefler SR, Mowlavi A, Suchy H, Boyle EM, Farr AL, Su CY, Frank N, Mulligan DC. 2001. Inhibition of the initial wave of NF-κB activity in rat muscle reduces ischemia/reperfusion injury. Muscle Nerve 24: 534-541.
93.Lindquist S, Craig EA. 1988. The heat shock proteins. Annu Rev Genet 22: 631-677.
94.Linnik M, Zorrist RH, Hatfield MD. 1993. Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 24: 2002-2009.
95.Lintott P, Hafez HM, Stansby G. 1998. Spinal cord complications of thoracoabdominal aneurysm surgery. Br J Surg 85: 5-15.
96.Lips J, de Haan P, Bouma GJ, Jacobs MJ, Kalkman CJ. 2002. Delayed detection of motor pathway dysfunction after selective reduction of thoracic spinal cord blood flow in pigs. J Thorac Cardiovasc Surg 123: 531-538.
97.Liu SF, Ye X, Malik AB. 1999. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes. Circulation 100: 1330-1337.
98.Liu Y, Lormes W, Baur C, Opitz-Gress A, Altenburg D, Lehmann M, Steinacker JM. 2000. Human skeletal muscle HSP70 response to physical training depends on exercise intensity. Int J Sports Med 21: 351-355.
99.Livesay JJ, Cooley DA, Ventemiglia RA, Montero CG, Warrian RK, Brown DM, Duncan JM. 1985. Surgical experience in descending thoracic aneurysmectomy with and without adjuncts to avoid ischemia. Ann Thorac Surg 39: 37-46.
100.Locke M, Noble EG, Atkinson BG. 1991. Inducible isoform of HSP70 is constitutively expressed in a muscle fiber type specific pattern. Am J Physiol 261: C774-779.
101.Mackey ME, Wu Y, Hu R, DeMaro JA, Jacquin MF, Kanellopoulos GK, Hsu CY, Kouchoukos NT. 1997. Cell death suggestive of apoptosis after spinal cord ischemia in rabbits. Stroke 28: 2012-2017.
102.MacManus JP, Linnik MD. 1997. Gene expression induced by cerebral ischemia: an apoptotic perspective. J Cereb Blood Flow Metab 17: 815-832.
103.Macnab I, Cuthbert H, Godfrey CM. 1977. The incidence of denervation of the sacrospinales muscles following spinal surgery. Spine 2: 294-298.
104.Maroney AC, Glicksman MA, Basma AN, Walton KM, Knight Jr E, Murphy CA, Bartlett BA, Finn JP, Angeles T, Matsuda Y, Neff NT, Dionne CA. 1998. Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signalling pathway. J Neurosci 18: 104-111.
105.Marsala M, Yaksh TL. 1994. Transient spinal ischemia in the rat: characterization of behavioral and histopathological consequences as a function of the duration of aortic occlusion. J Cereb Blood Flow Metab 14: 526-535.
106.Marsala M, Sorkin LS, Yaksh TL. 1994. Transient spinal ischemia in rat: characterization of spinal cord blood flow, extracellular amino acid release, and concurrent histopathological damage. J Cereb Blood Flow Metab 14: 604-614.
107.Martin SJ, Green DR. 1995. Protease activation during apoptosis: death by a thousand cuts. Cell 82: 1-4.
108.Matsushita K, Wu Y, Qiu J, Lang-Lazdunski L, Hirt L, Waeber C, Hyman BT, Yuan J, Moskowitz MA. 2000. Fas receptor and neuronal cell death after spinal cord ischemia. J Neurosci 20: 6879-6887.
109.Mayer TG, Vanharanta H, Gatchel RJ, Moony V, Barnes D, Judge L, Smith S, Terry A. 1989. Comparison of CT scan muscle measurements and isokinetic trunk strength in postoperative patients. Spine 14: 33-36.
110.Mielke K, Herdegen T. 2000. JNK and p38 stress kinase: degenerative effectors of signal transduction cascades in the nervous system. Prog Neurobiol 61: 45-60.
111.Mori T, Wang X, Jung JC, Sumii T, Singhal AB, Fini ME, Dixon CE, Alessandrini A, Lo EH. 2002. Mitogen-activated protein kinase inhibition in traumatic brain injury: in vitro and in vivo effects. J Cereb Blood Flow Metab 22: 444-452.
112.Morishima Y, Gotoh Y, Zieg J, Barrett T, Takano H, Flavell R, Davis RJ, Shirasaki Y, Greenberg ME. 2001. Β-amyloid induces neuronal apoptosis via a machanism that involve the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci 21: 7551-7560.
113.Murray B, Alessandrini A, Cole AJ, Yee AG, Furshpan EJ. 1998. Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity. Proc Natl Acad Sci USA 95: 11975-11980.
114.Nakahara S, Yone K, Sakou T, Wada S, Nagamine T, Niiyama T, Ichijo H. 1999. Induction of apoptosis signal regulating kinase 1 (ASK 1) after spinal cord injury in rats: possible involvement of ASK 1-JNK and –p38 pathways in neuronal apoptosis. J Neuropathol Exp Neurol 58: 442-450.
115.Nakajima W, Ishida A, Lange MS, Gabrielson KL, Wilson MA, Martin LJ, Blue ME, Johnston MV. 2000. Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat. J Neurosci 20: 7994-8004.
116.Namgung U, Xia Z. 2000. Arsenite-induced apoptosis in cortical neurons is mediated by c-Jun N-terminal protein kinase 3 and p38 mitogen-activated protein kinase. J Neurosci 20: 6442-6451.
117.Namura S, Zhu J, Fink K, Endres M, Srinvasan S, Tomaselli KJ, Yuan J, Moskowitz MA. 1998. Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci 18: 3659-3668.
118.Namura S, Iihara K, Takami S, Nagata I, Kikuchi H, Matsushita K, Moskowitz MA, Bonventre JV, Alessandrini A. 2001. Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc Natl Acad Sci USA 98: 11569-11574.
119.Naylor A. 1974. The late results of laminectomy for lumbar disc prolapse: a review after ten to twenty-five years. J Bone Joint Surg 56B: 17-29.
120.Nie Z, Mei Y, Ford M, Rybak L, Marcuzzi A, Ren H, Stiles GL, Ramkumar V. 1998. Oxidative stress increases A1 adenosine receptor expression by activating nuclear factor κB. Mol Pharmacol 53: 663-669.
121.Nishida E, Gotoh Y. 1993. The MAP kinase cascade is essential for diverse signal transduction pathways. Trends Biochem Sci 18: 128-131.
122.Northington FJ, Ferriero DM, Flock D, Martin LJ. 2001. Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis. J Neurosci 21: 1931-1938.
123.Nozaki K, Nishimura M, Hashimoto N. 2001. Mitogen-activated kinases and cerebral ischemia. Mol Neurobiol 23: 1-19.
124.Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358.
125.O’Neill GP, Ford-Hutchinson AW. 1993. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 330: 156-160.
126.Pahl HL. 1999. Activatiors and target genes of Rel/ NF-κB transcription factors. Oncogene 18: 6853-6866.
127.Prem JT, Eppinger M, Lemmon G, Miller S, Nolan D, Peoples J. 1999. The role of glutamine in skeletal muscle ischemia/reperfusion injury in the rat hind limb model. Am J Surg 178: 147-150.
128.Pulera MR, Adams LM, Liu H, Santos DG, Nishimura RN, Yang F, Cole GM, Wasterlain CG. 1998. Apoptosis in a neonatal rat model of cerebral hypoxia-ischemia. Stroke 29: 2622-2630.
129.Rantanen J, Hurme M, Falck B, Alaranta H, Nykvist F, Lehto M, Einola S, Kalimo H. 1993. The lumbar multifidus muscle five years after surgery for a lumbar intervertebral disc herniation. Spine 18: 568-574.
130.Rathore N, Kale JM, Bhatnagar D. 1998. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 38: 297-303.
131.Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV. 1995. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 83: 1243-1252.
132.Roy M, Deveraux QL, Takahashi R, Salvesen GS, Reed JC. 1997. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J 16: 6914-6925.
133.Rubin BB, Romaschin A, Walker PM, Gute DC, Korthuis RJ. 1996. Mechanisms of postischemic injury in skeletal muscle: intervention strategies. J Appl Physiol 80: 369-387.
134.Runden E, Seglen PO, Haug FM, Otterson OP, Wieloch T, Shamloo M, Laake JH. 1998. Regional selective neuronal degeneration after protein phosphotase inhibition in hippocampal slice cultures: evidence for a MAP kinase-dependent mechanism. J Neurosci 18: 7296-7305.
135.Rupec RA, Baeuerle PA. 1995. The genomic response of tumor cells to hypoxia and reoxygenation. Differential activation of transcription factors AP-1 and NF-kappa B. Eur J Biochem 234: 632-640.
136.Sakamoto A, Ohnishi T, Ohnishi T, Ogawa R. 1991. Relationship between free radical production and lipid peroxidation during ischemia-reperfusion injury in the rat brain. Brain Res 554: 186-192.
137.Sakurai M, Hayashi T, Abe K, Sadahiro M, Tabayashi K. 1998. Delayed and selective motor neuron death after transient spinal cord ischemia: a role of apoptosis? J Thorac Cardiovasc Surg 115: 1310-1315.
138.Salva U, Appel HJ, Sporn PHS, Waters CM. 2001. Prostaglandin E2 regulates wound closure in airway epithelium. Am J Physiol Lung Cell Mol Physiol 280: L421-L431.
139.Santoro MG. 2000. Heat shock factors and the control of the stress response. Biochem Pharmacol 59: 55-63.
140.Satoh T, Nakatsuka D, Watanabe Y, Nagata I, Kikuchi H, Namura S. 2000. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neurosci Lett 288: 163-166.
141.Schauwecker PE. 2000. Seizure-induced neuronal death is associated with induction of c-Jun N-terminal kinase and is dependent on genetic background. Brain Res 884: 116-128.
142.Schreck R, Albermann K, Baeuerle PA. 1992. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells. Free Radic Res Commun 17: 221-237.
143.Segal RA, Greenberg ME. 1996. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 19: 463-489.
144.Sgambato V, Pages C, Rogard M, Besson MJ, Caboche J. 1998. Extracellular signal-regulated kinase (ERK) controls immediate early gene induction on corticostriatal stimulation. J Neurosci 18: 8814-8825.
145.Shackelford DA, Yeh RY. 2001. Differential effects of ischemia and reperfusion on c-Jun N-terminal kinase isoform protein and activity. Mol Brain Res 94: 178-192.
146.Sihvonen T, Herno A, Paljarvi L, Airaksinen O, Partanen J, Tapaninaho A. 1993. Local denervation atrophy of paraspinal muscles in postoperative failed back syndrome. Spine 18: 575-581.
147.Singh U, Silver JR, Welpy NC. 1994. Hypotensive infarction of the spinal cord. Paraplegia 32: 314-322.
148.Sinnhuber RO, Yu TC. 1957. 2-Thiobarbituric acid method for the measurement of rancidity in fishery products: II. The quantitative determination of malonaldehyde. Food Tech 12: 9-12.
149.Stanciu M, Wang Y, Kentor R, Burke N, Watkins S, Kress G, Reynolds I, Klann E, Angiolieri MR, Johnson JW, DeFranco DB. 2000. Persitent activation of ERK contributes to glutamate induced oxidative toxicity in a neuronal cell line and primary neuron cultures. J Biol Chem 275: 12200-12206.
150.Sugino T, Nozaki K, Takagi Y, Hattori I, Hashimoto N, Moriguchi T, Nishida E. 2000. Activation of mitogen-activated protein kinases after transient forebrain ischemia in gerbil hippocampus. J Neurosci 20: 4506-4514.
151.Suwa H, Hanakita J, Ohshita N, Gotoh K, Matsuoka N, Morizane A. 2000. Postoperative changes in paraspinal muscle thickness after various lumbar back surgery procedures. Neurol Med Chir (Tokyo) 40: 151-155.
152.Svensson LG., Rickards E, Coull A, Rogers G, Fimmel CJ, Hinder RA. 1986. Relationship of spinal cord blood flow to vascular anatomy during thoracic cross-clamping and shunting. J Thorac Cardiovasc Surg 91: 71-78.
153.Svensson LG., Crawford ES, Patel V, Jones JW, DeBakey ME. 1992. Spinal cord oxygenation, intraoperative blood supply localization, cooling and function with aortic clamping. Ann Thorac Surg 54: 74-79.
154.Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi H. 1993. Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg 17: 357-370.
155.Tewari M, Quan LT, O’Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvensen GS, Dixit VM. 1995. Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 81: 801-809.
156.Thompson BG., Oldfield EH. 1995. Spinal vascular malformations, in Cater, L. P., Spetzler, R. F. (Eds), Neurovascular Surgery. McGraw-Hill Inc., New York, pp, 1167-1195.
157.Turner NA, Xia F, Azhar G, Zhang X, Liu L, Wei JY. 1998. Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J Mol Cell Cardiol 30: 1789-1810.
158.Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL. 1996. Cloning and expression of apoptosis inhibitory ptorein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA 93: 4974-4978.
159.Velier JJ, Ellison JA, Kikly KK, Spera PA, Barone FC, Feuerstein GZ. 1999. Caspase-8 and caspase-3 are expressed by different populations of cortical neurons undergoing delayed cell death after focal stroke in the rat. J Neurosci 19: 5932-5941.
160.Wada T, Yao H, Miyamoto T, Mukai S, Yamamura M. 2001. Prevention and dectection of spinal cord injury during thoracic and thoracoabdominal aortic repairs. Ann Thorac Surg 72: 80-85.
161.Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS, Jr. 1998. NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680-1683.
162.Weber BR, Grob D, Dvorak J, Muntener M. 1997. Posterior surgical approach to the lumbar spine and its effect on the multifidus muscle. Spine 22: 1765-1772.
163.Weinstein JN, Rydevik BL, Rauschning W. 1992. Anatomic and technical considerations of pedicle screw fixation. Clin Orthop 284: 34-46.
164.Westergren H, Farooque M, Olsson Y, Holtz A. 2001. Spinal cord blood flow changes following systemic hypothermia and spinal cord compression injury: an experimental study in the rat using Laser-Doppler flowmetry. Spinal Cord 39: 74-84.
165.Xia Z, Dickens M, Rainegaud J, Davis RJ, Greeberg ME. 1995. Opposing effects of ERK and JUNK/p38 MAP kinase on apoptosis. Science 270:1326-1331.
166.Xue D, Horvitz HR. 1995. Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein. Nature 377: 248-251.
167.Yakovlev AG, Knoblach SM, Fan L, Fox GB, Goodnight R, Faden AI. 1997. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J Neurosci 17: 7415-7424.
168.Yeh PY, Chuang SE, Yeh KH, Song YC, Ea CK, Cheng AL. 2002. Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NF-κB activation. Biochem Pharmacol 63: 1423-1430.
169.Zeiss CJ, Shomer NH, Homberger FR. 2001. Hypotensive infarction of the spinal cord in a rhesus macaque (Macaca mulatta). Vet Pathol 38:105-108.
170.Zipfel GJ, Babcock DJ, Lee JM, Choi DW. 2000. Neuronal apoptosis after CNS injury: the roles of glutamate and calcium. J Neurotrauma 17: 857-869.