Models of CNS injury in the nonhuman primate: A new era for treatment strategies

Walter de Gruyter GmbH - Tập 3 - Trang 181-195 - 2012
Leon Teo1, Jeffrey V. Rosenfeld2,3, James A. Bourne
1Australian Regenerative Medicine Institute, Monash University, Clayton, Australia
2Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia
3Department of Neurosurgery, The Alfred Hospital, Melbourne, Australia

Tóm tắt

Central nervous system (CNS) injuries affect all levels of society indiscriminately, resulting in functional and behavioral deficits with devastating impacts on life expectancies, physical and emotional wellbeing. Considerable literature exists describing the pathophysiology of CNS injuries as well as the cellular and molecular factors that inhibit regrowth and regeneration of damaged connections. Based on these data, numerous therapeutic strategies targeting the various factors of repair inhibition have been proposed and on-going assessment has demonstrated some promising results in the laboratory environ. However, several of these treatment strategies have subsequently been taken into clinical trials but demonstrated little to no improvement in patient outcomes. As a result, options for clinical interventions following CNS injuries remain limited and effective restorative treatment strategies do not as yet exist. This review discusses some of the current animal models, with focus on nonhuman primates, which are currently being modeled in the laboratory for the study of CNS injuries. Last, we review the current understanding of the mechanisms underlying repair/regrowth inhibition and the current trends in experimental treatment strategies that are being assessed for potential translation to clinical applications.

Tài liệu tham khảo

Morganti-Kossmann M. C., Yan E., Bye N., Animal models of traumatic brain injury: is there an optimal model to reproduce human brain injury in the laboratory? Injury, 2010, 41,Suppl. 1, S10–S13 Eltzschig H. K., Eckle T., Ischemia and reperfusion — from mechanism to translation, Nat. Med., 2011, 17, 1391–1401 Onifer S. M., Smith G. M., Fouad K., Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it, Neurotherapeutics, 2011, 8, 283–293 Lai M. C., Yang S. N., Perinatal hypoxic-ischemic encephalopathy, J. Biomed. Biotechnol., 2011, 609813 Coronado V. G., Xu L., Basavaraju S. V., McGuire L. C., Wald M. M., Faul M. D., Guzman B. R., et al., Surveillance for traumatic brain injuryrelated deaths - United States, 1997–2007, MMWR Surveill. Summ., 2011, 60, 1–32 Foundation for spinal cord injury prevention, C. A. C., Spinal cord injury facts [online]. Available: http://www.fscip.org/facts.htm [accessed 2 March 2012] Smith J., Wells L., Dodd K., The continuing fall in incidence of hypoxicischemic encephalopathy in term infants, BJOG, 2000, 107, 461–466 Williams G. R., Jiang J. G., Matchar D. B., Samsa G. P., Incidence and occurrence of total (first-ever and recurrent) stroke, Stroke, 1999, 30, 2523–2528 Narayan R. K., Michel M. E., Ansell B., Baethmann A., Biegon A., Bracken M. B., et al., Clinical trials in head injury, J. Neurotrauma, 2002, 19, 503–557 Millen J. E., Glauser F. L., Fairman R. P., A comparison of physiological responses to percussive brain trauma in dogs and sheep, J. Neurosurg., 1985, 62, 587–591 Pfenninger E. G., Reith A., Breitig D., Grunert A., Ahnefeld F. W., Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: An experimental study of the underlying pathophysiology, J. Neurosurg., 1989, 70, 774–779 Vink R., Bahtia K. D., Reilly P. L., The relationship between intracranial pressure and brain oxygenation following brain injury in sheep, Acta Neurochir. Suppl., 102, 189–192 Boyce V. S., Tumulo M., Fischer I., Murray M, Lemay M. A., Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats, J. Neurophysiol., 2007, 98, 1988–1996 Jefferson S. C., Tester N. J., Howland D. R., Chondroitinase ABC promotes recovery of adaptive limb movements and enhances axonal growth caudal to a spinal hemisection, J. Neurosci., 2011, 5710–5720 Kishimoto N., Shimizu K., Sawamoto K., Neuronal regeneration in a zebrafish model of adult brain injury, Dis. Model. Mech., 2012, 5, 200–209 Inder T., Neil J., Yoder B., Rees S., Non-human primate models of neonatal brain injury, Semin. Perinatol., 2004, 28, 396–404 De Crespigny A., J., D’Arceuil H. E., Maynard K. I., He J., McAuliffe D., Norbach A., Sehgal P. K., et al., Acute studies of a new primate model of reversible middle cerebral artery occlusion, J. Stroke Cerebrovasc. Dis., 2005, 14, 80–87 Fukuda S, Del Zoppo G., Models of focal cerebral ischemia in the nonhuman primate, ILAR J., 2003, 44, 96–104 Felleman D. J., Van Essen D. C., Distributed hierarchical processing in the primate cerebral cortex, Cereb. Cortex, 1991, 1, 1–47 Rosa M. G., Visual maps in the adult primate cerebral cortex: some implications for brain development and evolution, Braz. J. Med. Biol. Res., 2002, 35, 1485–1498 Schmid M. C., Mrowka S. W., Turchi J., Saunders R. C., Wilke M., Peters A. J., et al., Blindsight depends on the lateral geniculate nucleus, Nature, 2010, 466, 373–377 Fonta C., Imbert M., Vascularization in the primate visual cortex during development, Cereb. Cortex, 2002, 12, 199–211 Virley D., Hadingham S. J., Roberts J. C., Farnfield B., Elliott H., Whelan G., et al., A new primate model of focal stroke: endothelin-1-induced middle cerebral artery occlusion and reperfusion in the common marmoset, J. Cereb. Blood Flow Metab., 2004, 24, 24–41 Schwartz A. E., Pile-Spellman J., New model of reperfused stroke by occlusion of the anterior cerebral artery in baboons, Acta Neurochir. (Wien), 2011, 153, 327–331 Garcia J. H., Kamijyo Y., Cerebral infarction. Evolution of histopathological changes after occlusion of a middle cerebral artery in primates, J. Neuropathol. Exp. Neurol., 1974, 33, 408–421 Crowell R. M., Marcoux F. W., DeGirolami U., Variability and reversibility of focal cerebral ischemia in unanesthetized monkeys, Neurology, 1981, 31, 1295–1302 Spetzler R. F., Selman W. R., Weinstein P., Townsend J., Mehdorn M., Telles D., et al., Chronic reversible cerebral ischemia: evaluation of a new baboon model, Neurosurgery, 1980, 7, 257–261 Kito G., Nishimura A., Susumu T., Nagata R., Kuge Y., Yokota C., et al., Experimental thromboembolic stroke in cynomolgus monkey, J. Neurosci. Methods, 2001, 105, 45–53 Dunn I. F., Kim A. H., Gormley W. B., Brain trauma, In: Encyclopedia of neuroscience (ed. Larry R. S.), Oxford: Academic Press, 2009 Meythaler J. M., Peduzzi J. D., Eleftheriou E., Novack T. A., Current concepts: Diffuse axonal injury associated traumatic brain injury, Arch. Phys. Med. Rehab., 2001, 82, 1461–1471 Cernak I., Animal models of head trauma, NeuroRx, 2005, 2, 410–422 Weber J. T., Experimental models of repetitive brain injuries, Prog. Brain Res., 2007, 161, 253–261 Goldshmit Y., Bourne J., Upregulation of EphA4 on astrocytes potentially mediates astrocytic gliosis after cortical lesion in the marmoset monkey, J. Neurotrauma, 2010, 27, 1321–1332 Rosenfeld J. V., A neurosurgeon in Iraq: a personal perspective, J. Clin. Neurosci., 2006, 13, 986–990 Foroughi M., Kemeny A. A., Lehecka M., Wons J., Kajdi L., Hatfield R., et al., Operative intervention for delayed symptomatic radionecrotic masses developing following stereotactic radiosurgery for cerebral arteriovenous malformations — case analysis and literature review, Acta Neurochir. (Wien), 2010, 152, 803–815 Moseley B. D., Nickels K., Wirrell E. C., Surgical outcomes for intractable epilepsy in children with epileptic spasms, J. Child Neurol., 2011, [Epub ahead of print] Kazama A., Bechevalier J., Selective aspiration or neurotoxic lesions of orbital frontal areas 11 and 13 spared monkeys’ performance on the object discrimination reversal task, J. Neurosci., 2009, 29, 2794–2804 Rudebeck P. H., Murray E. A., Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning, J. Neurosci., 2008, 28, 8338–8343 Rudebeck P. H., Murray E. A., Dissociable effects of subtotal lesions within the macaque orbital prefrontal cortex on reward-guided behavior, J. Neurosci., 2011, 31, 10569–10578 Gennarelli T. A., Thibault L. E., Adams J. H., Graham D. I., Thompson C. J., Marcincin R. P., Diffuse axonal injury and traumatic coma in the primate, Ann. Neurol., 1982, 12, 564–574 Hofman M. A., Size and shape of the cerebral cortex in mammals. I. The cortical surface, Brain Behav. Evol., 1985, 27, 28–40 Hofman M. A., Size and shape of the cerebral cortex in mammals. II. The cortical volume, Brain Behav. Evol., 1988, 32, 17–26 Zhang K., Sejnowski T. J., A universal scaling law between gray matter and white matter of cerebral cortex, Proc. Natl. Acad. Sci. USA, 2000, 97, 5621–5626 Herculano-Houzel S., Mota B., Wong P., Kaas J. H., Connectivity-driven white matter scaling and folding in primate cerebral cortex, Proc. Natl. Acad. Sci. USA, 2010, 107, 19008–19013 Kadhim H., Sebire G., Kahn A., Evrad P., Dan B., Causal mechanisms underlying periventricular leukomalacia and cerebral palsy, Curr. Ped. Rev., 2005, 1, 1–6 Bergman I, Bauer R. E., Barmada M. A., Latchaw R. E., Taylor H. G., David R., et al., Intracerebral hemorrhage in the full-term neonatal infant, Pediatrics, 1985, 75, 488–496 Zhang Y. W., Chen Y. H., [Effects of hypoxia-ischemia on differential neural cells in subventricular zone of human fetus], Zhonghua Er. Ke. Za. Zhi., 2008, 46, 644–647 Morales P., Fiedler J. L., Andres S., Berrios C., Huaiquin P., Bustamante D., et al., Plasticity of hippocampus following perinatal asphyxia: effects on postnatal apoptosis and neurogenesis, J. Neurosci. Res., 2008, 86, 2650–2662 Perlman J. M., Summary proceedings from the neurology group on hypoxic-ischemic encephalopathy, Pediatrics, 2006, 117, S28–S33 Sloper J. J., Johnson P., Powell T. P. S., Selective degeneration of interneurons in the motor cortex of infant monkeys following controlled hypoxia: a possible cause of epilepsy, Brain Res., 1980, 198, 204–209 Myers R. E., Atrophic cortical sclerosis associated with status marmoratus in a perinatally damaged monkey, Neurology, 1969, 19, 1177–1188 Myers R. E., Two patterns of perinatal brain damage and their conditions of occurrence, Am. J. Obstet. Gynecol., 1972, 112, 246–276 Myers R. E., A unitary theory of causation of anoxic and hypoxic brain pathology, Adv. Neurol., 1979, 26, 195–213 Adamsons K., Mueller-Heubach E., Myers R.E., Production of fetal asphyxia in the rhesus monkey by administration of catecholamines to the mother, Am. J. Obstet. Gynecol., 1971, 109, 248–262 Brann A. W. Jr., Myers R. E., Cental nervous system findings in the newborn monkey following severe in utero partial asphyxia, Neurology, 1975, 25, 327–338 Inder T., Neil J., Yoder B., Rees S., Non-human primate models of neonatal brain injury. Semin. Perinatol., 2004, 28, 396–404 Hagberg H., Ichord R., Palmer C., Yager J. Y., Vannucci S. J., Animal models of developmental brain injury: relevance to human disease. A summary of the panel discussion from the Third Hershey Conference on developmental cerebral blood flow and metabolism, Dev. Neurosci., 2002, 24, 364–366 Yager J. Y., Ashwal S., Animal models of perinatal hypoxic-ischemic brain damage, Pediatr. Neurol., 2009, 40, 156–167 Lemons M. L., Howland D. R., Anderson D. K., Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation, Exp. Neurol., 1999, 160, 51–65 Merkler D., Metz G. A., Raineteau O., Dietz V., Schwab M. E., Fouad K., Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-A., J. Neurosci., 2001, 21, 3665–3673 Raineteau O., Fouad K., Bareyre F. M., Schwab M. E., Reorganization of descending motor tracts in the rat spinal cord, Eur. J. Neurosci., 2002, 16, 1761–1771 Gonzenbach R. R., Gasser P., Zorner B., Hochreutener R., Dietz V., Schwab M. E., Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats, Ann. Neurol., 2010, 68, 48–57 Darian-Smith C., Brown S., Functional changes at periphery and cortex following dorsal root lesions in adult monkeys, Nat. Neurosci., 2000, 3, 476–481 Babu R. S., Muthusamy R., Namasivayam A., Behavioural assessment of functional recovery after spinal cord hemisection in the bonnet monkey (Macaca radiate), J. Neurol. Sci., 2000, 178, 136–152 Babu R. S., Namasivayam A, Sridevi D., Periasamy P., Sunandhini R. L., Locomotor behavior of bonnet monkeys after spinal contusion injury: footprint study, Synapse, 2012, 66, 509–521 Babu R. S., Anand P., Jeraud M., Periasamy P., Namasivayam A., Bipedal locomotion of bonnet macaques after spinal cord injury, Motor Control, 2007, 11, 322–347 Babu R. S., Periasamy P., Varadamurthy S., Sethuraman O. S., Namasivayam A, Locomotor behavior of bonnet macaques after spinal cord injury, Motor Control, 2007, 11, 71–85 Babu R. S., Namasivayam A., Recovery of bipedal locomotion in bonnet macaques after spinal cord injury: footprint analysis, Synapse, 2008, 62, 432–447 Nout Y. S., Ferguson A. R., Strand S. C., Moseanko R., Hawbecker S., Zdunowski S., et al., Methods for functional assessment after C7 spinal cord hemisection in the rhesus monkey, Neurorehabil. Neural Repair, 2012, [Epub ahead of print] Valent L., Dallmeijer A., Houdijk H., Talsma E., Van der Woude L., The effects of upper body exercise on the physical capacity of people with a spinal cord injury: a systematic review, Clin. Rehabil., 2007, 21, 315–330 Valent L. J., Dallmeijer A. J., Houdijk H., Slootman H. J., Janssen T. W., Post M. W., et al., Effects of hand cycle training on physical capacity in individuals with tetraplegia: a clinical trial, Phys. Ther., 2009, 89, 1051–1060 Spooren A. I., Janssen-Potten Y. J., Kerckhofs E., Seelen H. A., Outcome of motor training programmes on arm and hand functioning in patients with cervical spinal cord injury according to different levels of the ICF: a systematic review, J. Rehabil. Med., 2009, 41, 497–505 Harvey L. A., Dunlop S. A., Churilov L., Hsueh Y. S., Galea M. P., Early intensive hand rehabilitation after spinal cord injury (“Hands on”): a protocol for a randomized controlled trial, Trials, 2011, 12, 14 Magnuson D. S., Smith R. R., Brown E. H., Enzmann G., Angeli C., Quesada P. M., et al., Swimming as a model of task-specific locomotor retraining after spinal cord injury in the rat, Neurorehabil. Neural Repair, 2009, 23, 535–545 Smith R. R., Brown E. H., Shum-Siu A., Whelan A., Burke D. A., Benton R. L., et al., Swim training initiated acutely after spinal cord injury is ineffective and induces extravasation in and around the epicenter, J. Neurotrauma, 2009, 26, 1017–1027 Onifer S. M., Zhang O., Whitnel-Smith L. K., Raza K., O’Dell C. R., Lyttle T., et al., Horizontal ladder task-specific re-training in adult rats with contusive thoracic spinal cord injury, Restor. Neurol. Neurosci., 2011, 29, 275–286 Nout Y. S., Rosenzweig E. S., Brock J. H., Strand S. C., Moseanko R., Hawbecker S., et al., Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury, Neurotherapeutics, 2012, 9, 380–392 Courtine G., Bunge M. B., Fawcett J. W., Grossman R. G., Kaas J. H., Lemon R., et al., Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?, Nat. Med., 2007, 13, 561–566 Lemon R. N., Griffiths J., Comparing the function of the corticospinal system in different species: organizational differences for motor specialization? Muscle Nerve, 2005, 32, 261–279 Del Zoppo G. J., Sharp F. R., Heiss W. D., Albers G. W., Heterogeneity in the penumbra, J. Cerebr. Blood Flow Metab., 2011, 31, 1836–1851 Broughton B. R., Reutens D. C., Sobey C. G., Apoptotic mechanisms after cerebral ischemia, Stroke, 2009, 40, e331–339 Kerr J. F., Wyllie A. H., Currie A. R., Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Br. J. Cancer, 1972, 26, 239–257 Yang Y., Rosenberg G. A., Blood-brain barrier breakdown in acute and chronic cerebrovascular disease, Stroke, 2011, 42, 3323–3328 Eugenin E. A., Berman J. W., Chemokine-dependent mechanism of leukocyte trafficking across a model of the blood-brain barrier, Methods, 2003, 29, 351–361 Aronowski J., Strong R., Grotta J. C., Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats, J. Cereb. Blood Flow Metab., 1997, 17, 1048–1056 O’Connell K. M., The role of free radicals in traumatic brain injury, Biol. Res. Nurs., 2012, [Epub ahead of print] Wang J. T., Medress Z. A., Barres B. A., Axon degeneration: molecular mechanisms of a self-destruction pathway, J. Cell Biol., 2012, 196, 7–18 Sun F., Lin C. L., McTigue D., Shan X., Tovar C. A., Bresnahan J. C., et al., Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis, Glia, 2010, 58, 1304–1319 Almad A., Sahinkaya F. R., McTigue D. M., Oligodendrocyte fate after spinal cord injury, Neurotherapeutics, 2011, 8, 262–273 Silver J., Miller J. H., Regeneration beyond the glial scar, Nat. Rev. Neurosci., 2004, 5, 146–156 Ramón y Cajal, S., Degeneration and regeneration of the nervous system, London: Oxford University Press, 1928 Waller A., Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres, Phil. Trans. R. Soc. Lond., 1850, 140, 423–429 Vargas M. E., Barres B. A., Why is Wallerian degeneration in the CNS so slow? Annu. Rev. Neurosci., 2007, 30, 153–179 Tom V., Steinmetz M. P., Miller J. H., Doller C. M., Silver J., Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury, J. Neurosci., 2004, 24, 6531–6539 David S., Aguayo A., Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats, Science, 1981, 214, 931–933 Blizzard C. A., Haas M. A., Vickers J. C., Dickson T. C., Cellular dynamics underlying regeneration of damaged axons differs from initial axon development, Eur. J. Neurosci., 2007, 26, 1100–1108 Blizzard C. A., King A. E., Haas M. A., O’Toole D. A., Vickers J. C., Dickson T. C., Axonal shearing in mature cortical neurons induces attempted regeneration and the reestablishment of neurite polarity, Brain Res., 2009, 1300, 24–36 Fawcett J. W., Overcoming inhibition in the damaged spinal cord, J. Neurotrauma, 2006, 23, 371–383 Galtrey C. M., Asher R. A., Nothias F., Fawcett J. W., Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair, Brain, 2007, 130, 926–939 Araque A., Carmignoto G., Haydon P. G., Dynamic signaling between astrocytes and neurons, Annu. Rev. Physiol., 2001, 63, 795–813 Fellin T., Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity, J. Neurochem., 2009, 108, 533–544 Goldshmit Y., Galea M. P., Wise G., Bartlett P. F., Turnley A. M., Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice, J. Neurosci., 2004, 24, 10064–10073 Dickson B. J., Rho GTPases in growth cone guidance, Curr. Opin. Neurobiol., 2001, 11, 103–110 Carbonell W. S., Mandell J. W., Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice, J. Neurotrauma, 2003, 20, 327–336 Fawcett J. W., Asher R. A., The glial scar and central nervous system repair, Brain Res. Bull., 1999, 49, 377–391 Smith-Thomas L. C., Fok-Seang J., Stevens J., Du J. S., Muir E., Faissner A., et al., An inhibitor of neurite outgrowth produced by astrocytes, J. Cell Sci., 1994, 107, 1687–1695 Fawcett J., Molecular control of brain plasticity and repair, Prog. Brain Res., 2009, 175, 501–509 Fryer H. J., Kelly G. M., Molinaro L., Hockfield S., The high molecular weight Cat-301 chondroitin sulfate proteoglycan from brain is related to the large aggregating proteoglycan from cartilage, aggrecan, J. Biol. Chem., 1992, 267, 9874–9883 Yiu G., He Z, Glial inhibition of CNS axon regeneration, Nat. Rev. Neurosci., 2006, 7, 617–627 Koppe G., Bruckner G., Brauer K., Hartig W., Bigl V., Developmental patterns of proteoglycan-containing extracellular matrix in perineuronal nets and neuropil of the postnatal rat brain, Cell Tissue Res., 1997, 288, 33–41 Matthews R. T., Kelly G. M., Zerillo C. A., Gray G., Tiemeyer M., Hockfield S., Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal nets, J. Neurosci., 2002, 22, 7536–7547 Giamanco K. A., Morawski M., Matthews R. T., Perineuronal net formation and structure in aggrecan knockout mice, Neuroscience, 2010, 170, 1314–1327 Murakami T., Ohtsuka A., Perisynaptic barrier of proteoglycans in the mature brain and spinal cord, Arch. Histol. Cytol., 2003, 66, 195–207 Bruckner G., Szeoke S., Pavlica S., Grosche J, Kacza J., Axon initial segment ensheated by extracellular matrix in perineuronal nets, Neuroscience, 2006, 138, 365–375 Bruckner G., Grosche J., Schmidt S., Hartig W., Margolis R. U., Delpech B., et al., Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R, J. Comp. Neurol., 2000, 428, 616–629 Bradbury E. J., Carter L. M., Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury, Brain Res. Bull., 2010, 84, 306–316 Bruckner G., Seeger G., Brauer K., Hartig W, Kacza J., Bigl V., Cortical areas are revealed by distribution patterns of proteoglycan components and parvalbumin in the Mongolian gerbil and rat, Brain Res., 1994, 658, 67–86 Deyoe E. A., Hockfield S., Garren H., Van Essen D. C., Antibody labeling of functional subdivisions in visual cortex: Cat-301 immunoreactivity in striate and extrastriate cortex of the macaque monkey, Vis. Neurosci., 1990, 5, 67–81 Homman-Ludiye J., Manger P. R., Bourne J. A., Immunohistochemical parcellation of the ferret (Mustela putorius) visual cortex reveals substantial homology with the cat (Felis catus), J. Comp. Neurol., 2010, 518, 4439–4462 Carull D., Laabs T., Geller H. M., Fawcett J. W., Chondroitin sulfate proteoglycans in neural development and regeneration, Curr. Opin. Neurobiol., 2005, 15, 116–120 Monnier P. P., Sierra A., Schwab J. M., Henke-Fahle S., Mueller B. K., The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar, Mol. Cell. Neurosci., 2003, 22, 319–330 Dickendesher T. L., Baldwin K. T., Mironova Y. A., Koriyama Y., Raiker S. J., Askew K. L., et al., NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans, Nat. Neurosci., 2012, 15, 703–712 Huber A. B., Weinmann O., Brosamle C., Oertle T., Schwab M. E., Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions, J. Neurosci., 2002, 22, 3553–3567 Mekhail M., Almazan G., Tabrizian M., Oligodendrocyte-protection and remyelination post-spinal injuries: A review, Prog. Neurobiol., 2012, 96, 322–339 Mukhopadhyay G., Doherty P., Walsh F. S., Crocker P. R., Filbin M. T., A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration, Neuron, 1994, 13, 757–767 McKerracher L., David S., Jackson D. L., Kottis V., Dunn R. J., Braun P. E., Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth, Neuron, 1994, 13, 805–811 Prinjha R., Moore S. E., Vinson M., Blake S., Morrow R., Christie G., et al., Inhibitor of neurite outgrowth in humans, Nature, 2000, 403, 383–384 Moreau-Fauvarque C., Kumanogoh A., Camand E., Jaillard C., Barbin G., Boquet I., et al., The transmembrane semaphoring Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion, J. Neurosci., 2003, 23, 9229–9239 Benson M. D., Romero M. I., Lush M.E., Lu Q. R., Henkemeyer M., Parada L. F., Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth, Proc. Natl. Acad. Sci. USA, 2005, 102, 10694–10699 Fournier A. E., Grandpre T., Strittmatter S. M., Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration, Nature, 2001, 409, 341–346 Atwal J. K., Pinkston-Gosse J., Syken J., Stawicki S, Wu Y., Shatz C., et al., PirB is a functional receptor for myelin inhibitors of axonal regeneration, Science, 2008, 322, 967–970 Fujita Y., Endo S., Takai T., Yamashita T., Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity, EMBO J., 2011, 1389–1401 Fujita Y., Takashima R., Endo S., Takai T., Yamashita T., The p75 receptor mediates axon growth inhibition through an association with PIR-B, Cell Death Dis., 2011, 2, e198 Nakamura Y., Fujita Y., Ueno M., Takai T., Yamashita T., Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury, J. Biol. Chem., 2011, 286, 1876–1883 Hunt D, Coffin R. S., Anderson P. N., The Nogo receptor, its ligands and axonal regeneration in the spinal cord: a review, J. Neurocytol., 2002, 31, 93–120 Domeniconi M., Cao Z., Spencer T., Sivasankaran R., Wang K., Nikulina E., et al., Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth, Neuron, 2002, 35, 283–290 Liu B. P., Fournier A., Grandpre T., Strittmatter S. M., Myelinassociated glycoprotein as a functional ligand for the Nogo-66 receptor, Science, 2002, 297, 1190–1193 Wang K., Koprivica V., Kim J. A., Sivasankaran R., Guo Y., Neve R. L., et al., Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth, Nature, 2002, 417, 941–944 Wang K. C., Kim J. A., Sivasankaran R., Segal R., He Z., P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and Omgp, Nature, 2002, 420, 74–78 Park J. B., Yiu G., Kaneko S., Wang J., Chang J., He X., et al., A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors, Neuron, 2005, 45, 345–351 Shao Z., Browning J. L., Lee X., Scott M. L., Shulga-Morskaya S., Allaire N., et al., TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration, Neuron, 2005, 45, 353–359 Mi S., Troy/Taj and its role in CNS axon regeneration, Cytokine Growth Factor Rev., 2008, 19, 245–251 Mi S., Sandrock A., Miller R. H., LINGO-1 and its role in CNS repair, Int. J. Biochem. Cell Biol., 2008, 40, 1971–1978 Zhang Z., Xu X., Zhang Y., Zhou J., Yu Z., He C., LINGO-1 interacts with WNK1 to regulate nogo-induced inhibition of neurite extension, J. Biol. Chem., 2009, 284, 15717–15728 Bourikas D., Mir A., Walmsley A. R., LINGO-1-mediated inhibition of oligodendrocyte differentiation does not require the leucinerich repeats and is reversed by p75(NTR) antagonists, Mol. Cell. Neurosci., 2010, 45, 363–369 Yamagata T., Saito H., Habuchi O., Suzuki S., Purification and properties of bacterial chondroitinases and chondrosulfatases, J. Biol. Chem., 1968, 243, 1523–1535 Suzuki S., Saito H., Yamagata T., Anno K., Seno N., Kawai Y., et al., Formation of three types of disulfated disaccharides from chondroitin sulfates by chondroitinase digestion, J. Biol. Chem., 1968, 243, 1543–1550 Koppe G., Bruckner G., Hartig W., Delpech B., Bigl V., Characterization of proteoglycan-containing perineuronal nets by enzymatic treatments of rat brain sections, Histochem. J., 1997, 29, 11–20 Bruckner G., Bringmann A., Hartig W., Koppe G., Delpech B., Brauer K., Acute and long-lasting changes in extracellular-matrix chondroitinsulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain, Exp. Brain Res., 1998, 121, 300–310 McKeon R. J., Hoke A., Silver J., Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars, Exp. Neurol., 1995, 136, 32–43 Bradbury E. J., Moon L. D. F., Popat R. J., King V. R., Bennett G. S., Patel P.N., et al., Chondroitinase ABC promotes functional recovery after spinal cord injury, Nature, 2002, 416, 636–640 Massey J. M., Hubscher C. H., Wagoner M. R., Decker J. A., Amps J., Silver J., et al., Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury, J. Neurosci., 2006, 26, 4406–4414 Wang D., Ichiyama R. M., Zhao R., Andrews M. R., Fawcett J. W., Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury, J. Neurosci., 2011, 31, 9332–9344 Garcia-Alias G., Barkhuysen S., Buckle M., Fawcett J. W., Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation, Nat. Neurosci., 2009, 12, 1145–1151 Tester N. J., Howland D. R., Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats, Exp. Neurol., 2008, 209, 483–496 Liebscher T., Schnell L., Schnell D., Scholl J., Schneider R., Gullo M., et al., Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats, Ann. Neurol., 2005, 58, 706–719 Fouad K., Klusman I., Schwab M. E., Regenerating corticospinal fibers in the Marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1, Eur. J. Neurosci., 2004, 20, 2479–2482 Freund P., Schmidlin E., Wannier T., Bloch J., Mir A., Schwab M. E., et al., Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates, Nat. Med., 2006, 12, 790–792 Freund P., Wannier T., Schmidlin E., Bloch J., Mir A., Schwab M. E., et al., Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey, J. Comp. Neurol., 2007, 502, 644–659 Grandpre T., Li S., Strittmatter S. M., Nogo-66 receptor antagonist peptide promotes axonal regeneration, Nature, 2002, 417, 547–551 Cao Y., Shumsky J. S., Sabol M. A., Kushner R. A., Strittmatter S., Hamers F. P., et al., Nogo-66 receptor antagonist peptide (NEP1–40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat, Neurorehabil. Neural Repair, 2008, 22, 262–278 Li S., Strittmatter S. M., Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury, J. Neurosci., 2003, 23, 4219–4227 Steward O., Sharp K, Yee K. M., Hofstadter M., A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice, Exp. Neurol., 2008, 209, 446–468 Zai L., Ferrari C., Dice C., Subbaiah S., Havton L. A., Coppola G., et al., Inosine augments the effects of a nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke, J. Neurosci., 2011, 31, 5977–5988 Zorner B., Schwab M. E., Anti-Nogo on the go: from animal models to a clinical trial, Ann. NY Acad. Sci., 2010, 1198(Suppl. 1), E22–E34 Yue Y., Su J., Cerretti D. P., Fox G. M., Jing S., Zhou R., Selective inhibition of spinal cord neurite outgrowth and cell survival by the Eph family ligand ephrin-A5, J. Neurosci., 1999, 19, 10026–10035 Wahl S., Barth H., Ciossek T., Aktories K., Mueller B. K., Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase, J. Cell Biol., 2000, 149, 263–270 Goldshmit Y., Spanevello M. D., Tajouri S., Li L., Rogers F., Pearse M., et al., EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice, PLoS One, 2011, 6, e24636 Fabes J., Anderson P., Brennan C., Bolsover S., Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord, Eur. J. Neurosci., 2007, 26, 2496–2505 Permentier-Batteur S., Finger E. N., Krishnan R., Rajapakse H. A., Sanders J. M., Kandpal G., et al., Attenuation of scratch-induced reactive astrogliosis by novel EphA4 kinase inhibitors, J. Neurochem., 2011, 118, 1016–1031 Jin Y., Fischer I., Tessler A., Houle J. D., Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury, Exp. Neurol., 2002, 177, 265–275 Liu Y., Himes B. T., Murray M., Tessler A., Fischer I., Grafts of BDNFproducing fibroblasts rescue axotomized rubrospinal neurons and prevent their atrophy, Exp. Neurol., 2002, 178, 150–164 Tobias C. A., Shumsky J. S., Shibata M., Tuszynski M. H., Fischer I., Tessler A., et al., Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration, Exp. Neurol., 2003, 184, 97–113 Boyce V. S., Park J., Gage F. H., Mendell L. M., Differential effects of brainderived neurotrophic factor and neurotropin-3 on hindlimb function in paraplegic rats, Eur. J. Neurosci., 2012, 35, 221–232 White R. E., Yin F. Q., Jakeman L. B., TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice, Exp. Neurol., 2008, 214, 10–24 White R. E., Rao M., Gensel J. C., McTigue D. M., Kaspar B. K., Jakeman L. B., Transforming growth factor alpha transforms astrocytes to a growth-supportive phenotype after spinal cord injury, J. Neurosci. 2011, 31, 15173–15187 Minnich J. E., Mann S. L., Stock M., Stolzenbach K. A., Mortell B. M., Soderstrom K. E., et al., Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects cortical neurons from dying following a traumatic brain injury, Restor. Neurol. Neurosci., 2010, 28, 293–309 DeGeorge M. L., Marlowe D., Werner E, Soderstrom K. E., Stock M, Mueller A., et al., Combining glial cell line-derived neurotrophic factor gene delivery (AdGNDF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury, Brain Res., 2011, 1403, 45–56 Monfils M. H., Driscoll I., Kamitakahara H., Wilson B., Flynn C, Teskey G. C., et al., FGF-2-induced cell proliferation stimulates anatomical, neurophysiological and functional recovery from neonatal motor cortex injury, Eur. J. Neurosci., 2006, 24, 739–749 Nemati F., Kolb B., FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats, Behav. Brain Res., 2011, 225, 184–191 Russell J. C., Szuflita N., Khatri R., Laterra J., Hossain M. A., Transgenic expression of human FGF-1 protects against hypoxic-ischemic injury in perinatal brain by intervening at caspase-XIAP signaling cascades, Neurobiol. Dis., 2006, 22, 677–690 Ming G. L., Song H., Adult neurogenesis in the mammalian central nervous system, Annu. Rev. Neurosci., 2005, 28, 223–250 Cameron H. A., Dayer A. G., New interneurons in the adult neocortex: small, sparse, but significant?, Biol. Psychiatry, 2008, 63, 650–655 Palmer T. D., Markakis E. A., Willhoite A. R., Safar F., Gage F. H., Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS, J. Neurosci., 1999, 19, 8487–8497 Homman-Ludiye J., Merson T., Bourne J., The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells, PLoS One, 2012, 7, e34383 Arsenijevic Y., Villemure J. G., Brunet J. F., Bloch J. J., Deglon N., Kostic C., et al., Isolation of multipotent neural precursors residing in the cortex of the adult human brain, Exp. Neurol., 2001, 170, 48–62 Arellano J. I., Rakic P., Neuroscience: gone with the wean, Nature, 2011, 478, 333–334 Sanai N, Nguyen T., Ihrie R. A., Mirzadeh Z., Tsai H. H., Wong M., et al., Corridors of migrating neurons in the human brain and their decline during infancy, Nature, 2011, 478, 382–386 Sidman R. L., Rakic P., Neuronal migration, with special reference to developing human brain: a review, Brain Res., 1973, 62, 1–35 Magavi S. S., Leavitt B. R., Macklis J. D., Induction of neurogenesis in the neocortex of adult mice, Nature, 2000, 405, 951–955 Buffo A., Rite I., Tripathi P., Lepier A., Colak D, Horn A. P., et al., Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain, Proc. Natl. Acad. Sci. USA, 2008, 105, 3581–3586 Rosenzweig E. S., Courtine G., Jindrich D. L., Brock J. H., Ferguson A. R., Strand S. C., et al., Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury, Nat. Neurosci., 2010, 13, 1505–1510 Vessal M., Aycock A., Garton M. T., Ciferri M., Darian-Smith C., Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transaction, Eur. J. Neurosci., 2007, 26, 2777–2794 Vessal M., Darian-Smith C., Adult neurogenesis occurs in primate sensorimotor cortex following cervical dorsal rhizotomy, J. Neurosci., 2010, 30, 8613–8623 Thuret S., Moon L. D., Gage F. H., Therapeutic interventions after spinal cord injury, Nat. Rev. Neurosci., 2006, 7, 628–643 Iwanami A., Kaneko S., Nakamura M, Kanemura Y., Mori H., Kobayashi S., et al., Transplantation of human neural stem cells for spinal cord injury in primates, J. Neurosci. Res., 2005, 80, 182–190 Daadi M. M., Davis A. S., Arac A., Li Z., Maag A. L., Bhatnagar R., et al., Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury, Stroke, 2010, 41, 516–523 Lee I. S., Jung K., Kim M., Park K. I., Neural stem cells: properties and therapeutic potentials for hypoxic-ischemic brain injury in newborn infants, Pediatr. Int., 2010, 52, 855–865 Siqueira R. C., Stem cell therapy for retinal diseases: update, Stem Cell Res. Ther., 2011, 2, 50 Burns T. C., Verfaillie C. M., Low W. C., Stem cells for ischemic brain injury: a critical review, J. Comp. Neurol., 2009, 515, 125–144 Dong J., Liu B., Song L., Lu L., Xu H., Gu Y., Neural stem cells in the ischemic and injured brain: endogeneous and transplanted, Cell Tissue Bank., 2011, [Epub ahead of print] Jiang J. Bu X., Liu M., Cheng P., Transplantation of autologous bonemarrow- derived mesenchymal stem cells for traumatic brain injury, Neural Regener. Res., 2012, 7, 46–53 Haas S., Weidner N., Winkler J., Adult stem cell therapy in stroke, Curr. Opin. Neurol., 2005, 18, 59–64 Hu S.-L., Luo H.-S., Li J.-T., Xia Y.-Z., Li L., Zhang L.-J., et al., Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells, Crit. Care Med., 2010, 38, 2181–2189 Bretzner F., Gilbert F., Baylis F., Brownstone R. M., Target populations for first-in-human embryonic stem cell research in spinal cord injury, Cell Stem Cell, 2011, 8, 468–475 Wirth E. 3rd, Lebkowski J. S., Lebacqz K, Response to Frederic Bretzner et al. “Target populations for first-in-human embryonic stem cell research in spinal cord injury”, Cell Stem Cell, 2011, 8, 476–478 Brown E., Economics, not science, thwarts embryonic stem cell therapy, LA Times, 21 Nov. 2011 Kondziolka D., Wechsler L., Stroke repair with cell transplantation: neuronal cells, neuroprogenitor cells, and stem cells, Neurosurg. Focus, 2008, 24, e13 Harkema S. J., Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking, Neuroscientist, 2001, 7, 455–468 Nelles G., Esser J., Eckstein A., Tiede A., Gerhard H., Diener H. C., Compensatory visual field training for patients with hemianopia after stroke, Neurosci. Lett., 2001, 306, 189–192 Das A., Huxlin K. R., New approaches to visual rehabilitation for cortical blindness: outcomes and putative mechanisms, Neuroscientist, 2010, 16, 374–387 Trauzettel-Klosinski S., Current methods of visual rehabilitation, Dtsch. Arztebl. Int., 2011, 108, 871–878 Schnell L., Hunanyan A. S., Bowers W. J., Horner P. J., Federoff H. J., Gullo M., et al., Combined delivery of Nogo-A antibody, neurotrophin-3 and the NMDA-NR2d subunit establishes a functional ‘detour’ in the hemisected spinal cord, Eur. J. Neurosci., 2011, 34, 1256–1267 Garcia-Alias G., Petrosyan H. A., Schnell L., Horner P. J., Bowers W. J., Mendell L. M., et al., Chondroitinase ABC combined with neurotrophin NT-3 secretion and NR2D expression promotes axonal plasticity and functional recovery in rats with lateral hemisection of the spinal cord, J. Neurosci., 2011, 31, 17788–17799 Arvanian V. L., Bowers W. J., Anderson A., Horner P. J., Federoff H. J, Mendell L. M., Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat, Exp. Neurol., 2006, 197, 347–352