Targeting Microvasculature for Neuroprotection after SCI

被引:66
作者
Fassbender, Janelle M. [1 ,2 ,4 ]
Whittemore, Scott R. [1 ,3 ,4 ]
Hagg, Theo [1 ,3 ,5 ]
机构
[1] Univ Louisville, Kentucky Spinal Cord Injury Res Ctr, Sch Med, Louisville, KY 40292 USA
[2] Univ Louisville, MD Ph D Program, Sch Med, Louisville, KY 40292 USA
[3] Univ Louisville, Dept Neurol Surg, Sch Med, Louisville, KY 40292 USA
[4] Univ Louisville, Dept Anat Sci & Neurobiol, Sch Med, Louisville, KY 40292 USA
[5] Univ Louisville, Dept Pharmacol & Toxicol, Sch Med, Louisville, KY 40292 USA
基金
美国国家卫生研究院;
关键词
Spinal cord injury; therapeutics; neuroprotection; vasculature; inflammation; SPINAL-CORD-INJURY; ENDOTHELIAL GROWTH-FACTOR; BLOOD-BRAIN-BARRIER; FOCAL CEREBRAL-ISCHEMIA; NERVOUS-SYSTEM TRAUMA; FUNCTIONAL RECOVERY; CONTUSION INJURY; REACTIVE ASTROCYTES; HEME OXYGENASE-1; IMPACT INJURY;
D O I
10.1007/s13311-011-0029-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Spinal cord injury (SCI) is characterized by secondary degeneration, which leads to tissue loss at the epicenter and subsequent functional deficits. This review provides insight into the pathophysiology of microvascular dysfunction and endothelial cell loss, which are among the earliest responses during the first postinjury day. The enigmatic role of the angiogenic response in the penumbra around the lost tissue, which occurs during the first 2 weeks, is also discussed. The importance of stabilizing and rescuing the injured vasculature is now well-recognized, and several pharmacological and genetic treatments have emerged in the past few years. We conclude with suggestions for future experimental research, including development of vascular-selective treatments and exploitation of genetic models. In summary, vascular dysfunction following SCI is an important contributor to neurological deficits, as proposed long ago. However, there now appears to be new and potentially powerful opportunities for treating acute SCI by targeting the vascular responses.
引用
收藏
页码:240 / 251
页数:12
相关论文
共 165 条
[1]   Structure and function of the blood-brain barrier [J].
Abbott, N. Joan ;
Patabendige, Adjanie A. K. ;
Dolman, Diana E. M. ;
Yusof, Siti R. ;
Begley, David J. .
NEUROBIOLOGY OF DISEASE, 2010, 37 (01) :13-25
[2]   Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration [J].
Alexander, Jessica K. ;
Popovich, Phillip G. .
NEUROTHERAPY: PROGRESS IN RESTORATIVE NEUROSCIENCE AND NEUROLOGY, 2009, 175 :125-137
[3]  
Allen A., 1911, J AM MED ASS, V57, P878, DOI [10.1001/jama.1911.04260090100008, DOI 10.1001/JAMA.1911.04260090100008]
[4]   Remarks on the histopathological changes in the spinal cord due to impact - An experimental study [J].
Allen, AR .
JOURNAL OF NERVOUS AND MENTAL DISEASE, 1914, 41 :141-147
[5]   VE-cadherin-Cre-recombinase transgenic mouse: A tool for lineage analysis and gene deletion in endothelial cells [J].
Alva, JA ;
Zovein, AC ;
Monvoisin, A ;
Murphy, T ;
Salazar, A ;
Harvey, NL ;
Carmeliet, P ;
Iruela-Arispe, ML .
DEVELOPMENTAL DYNAMICS, 2006, 235 (03) :759-767
[6]   CADASIL Pathogenesis, clinical and radiological findings and treatment [J].
Andre, Charles .
ARQUIVOS DE NEURO-PSIQUIATRIA, 2010, 68 (02) :287-299
[7]   Ultrastructural evidence for arteriolar vasospasm after spinal cord trauma [J].
Piepmeier, JM .
NEUROSURGERY, 1996, 39 (04) :814-814
[8]   Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche [J].
Arai, F ;
Hirao, A ;
Ohmura, M ;
Sato, H ;
Matsuoka, S ;
Takubo, K ;
Ito, K ;
Koh, GY ;
Suda, T .
CELL, 2004, 118 (02) :149-161
[9]   Pericytes regulate the blood-brain barrier [J].
Armulik, Annika ;
Genove, Guillem ;
Mae, Maarja ;
Nisancioglu, Maya H. ;
Wallgard, Elisabet ;
Niaudet, Colin ;
He, Liqun ;
Norlin, Jenny ;
Lindblom, Per ;
Strittmatter, Karin ;
Johansson, Bengt R. ;
Betsholtz, Christer .
NATURE, 2010, 468 (7323) :557-U231
[10]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967