Stem cell biology in traumatic brain injury: effects of injury and strategies for repair

A review

Restricted access

Approximately 350,000 individuals in the US are affected annually by severe and moderate traumatic brain injuries (TBI) that may result in long-term disability. This rate of injury has produced ~ 3.3 million disabled survivors in the US alone. There is currently no specific treatment available for TBI other than supportive care, but aggressive prehospital resuscitation, rapid triage, and intensive care have reduced mortality rates. With the recent demonstration that neurogenesis occurs in all mammals (including man) throughout adult life, albeit at a low rate, the concept of replacing neurons lost after TBI is now becoming a reality. Experimental rodent models have shown that neurogenesis is accelerated after TBI, especially in juveniles. Two approaches have been followed in these rodent models to test possible therapeutic approaches that could enhance neuronal replacement in humans after TBI. The first has been to define and quantify the phenomenon of de novo hippocampal and cortical neurogenesis after TBI and find ways to enhance this (for example by exogenous trophic factor administration). A second approach has been the transplantation of different types of neural progenitor cells after TBI. In this review the authors discuss some of the processes that follow after acute TBI including the changes in the brain microenvironment and the role of trophic factor dynamics with regard to the effects on endogenous neurogenesis and gliagenesis. The authors also discuss strategies to clinically harness the factors influencing these processes and repair strategies using exogenous neural progenitor cell transplantation. Each strategy is discussed with an emphasis on highlighting the progress and limiting factors relevant to the development of clinical trials of cellular replacement therapy for severe TBI in humans.

Abbreviations used in this paper: BrdU = bromodeoxyuridine; CCI = controlled cortical impact; DAI = diffuse axonal injury; DG = dentate gyrus; FPI = fluid percussion injury; GABA = γ-Aminobutyric acid; hNT = human teratocarcinoma cell line; ICP = intracranial pressure; LFP = lateral fluid percussion; NGF = nerve growth factor; NPC = neural progenitor cell; NSC = neural stem cell; SCI = spinal cord injury; SVZ = subventricular zone; TBI = traumatic brain injury.
Article Information

Contributor Notes

Address correspondence to: M. Ross Bullock, M.D., Ph.D., Department of Neurosurgery, University of Miami, Miller School of Medicine, Lois Pope LIFE Center, Room 3-20, 1095 Northwest 14th Terrace, Miami, Florida 33136. email: rbullock@med.miami.edu.Please include this information when citing this paper: published online June 5, 2009; DOI: 10.3171/2009.4.JNS081087.

© Copyright 1944-2019 American Association of Neurological Surgeons

Headings
References
  • 1

    Adams JHDoyle DFord IGennarelli TAGraham DIMcLellan DR: Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15:49591989

    • Search Google Scholar
    • Export Citation
  • 2

    Alvarez-Buylla A: Neurogenesis and plasticity in the CNS of adult birds. Exp Neurol 115:1101141992

  • 3

    Alvarez-Buylla AGarcia-Verdugo JM: Neurogenesis in adult subventricular zone. J Neurosci 22:6296342002

  • 4

    Alvarez-Buylla ALim DA: For the long run: maintaining germinal niches in the adult brain. Neuron 41:6836862004

  • 5

    Ao QWang AJChen GQWang SJZuo HCZhang XF: Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries. Med Hypotheses 69:123412372007

    • Search Google Scholar
    • Export Citation
  • 6

    Arsenijevic YVillemure JGBrunet JFBloch JJDeglon NKostic C: Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Exp Neurol 170:48622001

    • Search Google Scholar
    • Export Citation
  • 7

    Bachoud-Levi ACGaura VBrugieres PLefaucheur JPBoisse MFMaison P: Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study. Lancet Neurol 5:3033092006

    • Search Google Scholar
    • Export Citation
  • 8

    Bakshi AShimizu SKeck CACho SLeBold DGMorales D: Neural progenitor cells engineered to secrete GDNF show enhanced survival, neuronal differentiation and improve cognitive function following traumatic brain injury. Eur J Neurosci 23:211921342006

    • Search Google Scholar
    • Export Citation
  • 9

    Becerra GDTatko LMPak ESMurashov AKHoane MR: Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain. Behav Brain Res 179:1181252007

    • Search Google Scholar
    • Export Citation
  • 10

    Bjorklund ADunnett SBBrundin PStoessl AJFreed CRBreeze RE: Neural transplantation for the treatment of Parkinson's disease. Lancet Neurol 2:4374452003

    • Search Google Scholar
    • Export Citation
  • 11

    Boockvar JASchouten JRoyo NMillard MSpangler ZCastelbuono D: Experimental traumatic brain injury modulates the survival, migration, and terminal phenotype of transplanted epidermal growth factor receptor-activated neural stem cells. Neurosurgery 56:1631712005

    • Search Google Scholar
    • Export Citation
  • 12

    Chirumamilla SSun DBullock MRColello RJ: Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma 19:6937032002

    • Search Google Scholar
    • Export Citation
  • 13

    Clark RSKochanek PMWatkins SCChen MDixon CESeidberg NA: Caspase-3 mediated neuronal death after traumatic brain injury in rats. J Neurochem 74:7407532000

    • Search Google Scholar
    • Export Citation
  • 14

    Dash PKMach SAMoore AN: Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury. J Neurosci Res 63:3133192001

    • Search Google Scholar
    • Export Citation
  • 15

    Driscoll IHoward SRStone JCMonfils MHTomanek BBrooks WM: The aging hippocampus: a multi-level analysis in the rat. Neuroscience 139:117311852006

    • Search Google Scholar
    • Export Citation
  • 16

    Dunnett SBNathwani FBjorklund A: The integration and function of striatal grafts. Prog Brain Res 127:3453802000

  • 17

    Edwards PArango MBalica LCottingham REl-Sayed HFarrell B: Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 365:195719592005

    • Search Google Scholar
    • Export Citation
  • 18

    Ekdahl CTClaasen JHBonde SKokaia ZLindvall O: Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 100:13632136372003

    • Search Google Scholar
    • Export Citation
  • 19

    Emery DLFulp CTSaatman KESchutz CNeugebauer EMcIntosh TK: Newly born granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury. J Neurotrauma 22:9789882005

    • Search Google Scholar
    • Export Citation
  • 20

    Eriksson PSPerfilieva EBjork-Eriksson TAlborn AMNordborg CPeterson DA: Neurogenesis in the adult human hippocampus. Nat Med 4:131313171998

    • Search Google Scholar
    • Export Citation
  • 21

    Falo MCFillmore HLReeves TMPhillips LL: Matrix metalloproteinase-3 expression profile differentiates adaptive and maladaptive synaptic plasticity induced by traumatic brain injury. J Neurosci Res 84:7687812006

    • Search Google Scholar
    • Export Citation
  • 22

    Feron FPerry CCochrane JLicina PNowitzke AUrquhart S: Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 128:295129602005

    • Search Google Scholar
    • Export Citation
  • 23

    Fitch MTSilver J: CNS injury, glial scars, and inflammation: inhibitory extracellular matrices and regeneration failure. Exp Neurol 2009:2943012008

    • Search Google Scholar
    • Export Citation
  • 24

    Freed CRGreene PEBreeze RETsai WYDuMouchel WKao R: Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 344:7107192001

    • Search Google Scholar
    • Export Citation
  • 25

    Gao JPrough DSMcAdoo DJGrady JJParsley MOMa L: Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury. Exp Neurol 201:2812922006

    • Search Google Scholar
    • Export Citation
  • 26

    Gennarelli TAGraham DI: Neuropathology of the head injuries. Semin Clin Neuropsychiatry 3:1601751998

  • 27

    Hagell PPiccini PBjorklund ABrundin PRehncrona SWidner H: Dyskinesias following neural transplantation in Parkinson's disease. Nat Neurosci 5:6276282002

    • Search Google Scholar
    • Export Citation
  • 28

    Hastings NBGould E: Rapid extension of axons into the CA3 region by adult-generated granule cells. J Comp Neurol 413:1461541999

  • 29

    He ZKoprivica V: The Nogo signaling pathway for regeneration block. Annu Rev Neurosci 27:3413682004

  • 30

    Heine VMMaslam SJoels MLucassen PJ: Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging 25:3613752004

    • Search Google Scholar
    • Export Citation
  • 31

    Hicks RRNuman SDhillon HSPrasad MRSeroogy KB: Alterations in BDNF and NT-3 mRNAs in rat hippocampus after experimental brain trauma. Brain Res Mol Brain Res 48:4014061997

    • Search Google Scholar
    • Export Citation
  • 32

    Hoane MRBecerra GDShank JETatko LPak ESSmith M: Transplantation of neuronal and glial precursors dramatically improves sensorimotor function but not cognitive function in the traumatically injured brain. J Neurotrauma 21:1631742004

    • Search Google Scholar
    • Export Citation
  • 33

    Ibrahim ALi YLi DRaisman GEl Masry WS: Olfactory ensheathing cells: ripples of an incoming tide?. Lancet Neurol 5:4534572006

    • Search Google Scholar
    • Export Citation
  • 34

    Itoh TSatou THashimoto SIto H: Isolation of neural stem cells from damaged rat cerebral cortex after traumatic brain injury. Neuroreport 16:168716912005

    • Search Google Scholar
    • Export Citation
  • 35

    Kelley BJLifshitz JPovlishock JT: Neuroinflammatory responses after experimental diffuse traumatic brain injury. J Neuropathol Exp Neurol 66:98910012007

    • Search Google Scholar
    • Export Citation
  • 36

    Kempermann GKuhn HGGage FH: Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 18:320632121998

  • 37

    Kendall ALHantraye PPalfi S: Striatal tissue transplantation in non-human primates. Prog Brain Res 127:3814042000

  • 38

    Kernie SGErwin TMParada LF: Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 66:3173262001

    • Search Google Scholar
    • Export Citation
  • 39

    Kleindienst AHarvey HBRice ACMuller CHamm RJGaab MR: Intraventricular infusion of the neurotrophic protein S100B improves cognitive recovery after fluid percussion injury in the rat. J Neurotrauma 21:5415472004

    • Search Google Scholar
    • Export Citation
  • 40

    Kleindienst AMcGinn MJHarvey HBColello RJHamm RJBullock MR: Enhanced hippocampal neurogenesis by intraventricular S100B infusion is associated with improved cognitive recovery after traumatic brain injury. J Neurotrauma 22:6456552005

    • Search Google Scholar
    • Export Citation
  • 41

    Kleindienst ARoss Bullock M: A critical analysis of the role of the neurotrophic protein S100B in acute brain injury. J Neurotrauma 23:118512002006

    • Search Google Scholar
    • Export Citation
  • 42

    Kondziolka DSteinberg GKWechsler LMeltzer CCElder EGebel J: Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 103:38452005

    • Search Google Scholar
    • Export Citation
  • 43

    Kondziolka DWechsler LGoldstein SMeltzer CThulborn KRGebel J: Transplantation of cultured human neuronal cells for patients with stroke. Neurology 55:5655692000

    • Search Google Scholar
    • Export Citation
  • 44

    Kornack DRRakic P: The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc Natl Acad Sci U S A 98:475247572001

    • Search Google Scholar
    • Export Citation
  • 45

    Kotapka MJGraham DIAdams JHGennarelli TA: Hippocampal pathology in fatal human head injury without high intracranial pressure. J Neurotrauma 11:3173241994

    • Search Google Scholar
    • Export Citation
  • 46

    Kotapka MJGraham DIAdams JHGennarelli TA: Hippocampal pathology in fatal non-missile human head injury. Acta Neuropathol 83:5305341992

    • Search Google Scholar
    • Export Citation
  • 47

    Kuhn HGDickinson-Anson HGage FH: Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:202720331996

    • Search Google Scholar
    • Export Citation
  • 48

    Laurer HLMcIntosh TK: Experimental models of brain trauma. Curr Opin Neurol 12:7157211999

  • 49

    Lenzlinger PMShimizu SMarklund NThompson HJSchwab MESaatman KE: Delayed inhibition of Nogo-A does not alter injury-induced axonal sprouting but enhances recovery of cognitive function following experimental traumatic brain injury in rats. Neuroscience 134:104710562005

    • Search Google Scholar
    • Export Citation
  • 50

    Leuner BGould EShors TJ: Is there a link between adult neurogenesis and learning?. Hippocampus 16:2162242006

  • 51

    Lie DCSong HColamarino SAMing GLGage FH: Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol 44:3994212004

    • Search Google Scholar
    • Export Citation
  • 52

    Lim DAHuang YCAlvarez-Buylla A: The adult neural stem cell niche: lessons for future neural cell replacement strategies. Neurosurg Clin N Am 18:8192ix2007

    • Search Google Scholar
    • Export Citation
  • 53

    Lindvall OBjorklund A: Cell therapy in Parkinson's disease. NeuroRx 1:3823932004

  • 54

    Lu DMahmood AQu CGoussev ASchallert TChopp M: Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury. J Neurotrauma 22:101110172005

    • Search Google Scholar
    • Export Citation
  • 55

    Lu DMahmood AZhang RCopp M: Upregulation of neurogenesis and reduction in functional deficits following administration of DEtA/NONOate, a nitric oxide donor, after traumatic brain injury in rats. J Neurosurg 99:3513612003

    • Search Google Scholar
    • Export Citation
  • 56

    Magavi SSLeavitt BRMacklis JD: Induction of neurogenesis in the neocortex of adult mice. Nature 405:9519552000

  • 57

    Manganas LNZhang XLi YHazel RDSmith SDWagshul ME: Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318:9809852007

    • Search Google Scholar
    • Export Citation
  • 58

    Manley GTRosenthal GLam MMorabito DYan DDerugin N: Controlled cortical impact in swine: pathophysiology and biomechanics. J Neurotrauma 23:1281392006

    • Search Google Scholar
    • Export Citation
  • 59

    Markakis EAGage FH: Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. J Comp Neurol 406:4494601999

    • Search Google Scholar
    • Export Citation
  • 60

    Marklund NBareyre FMRoyo NCThompson HJMir AKGrady MS: Cognitive outcome following brain injury and treatment with an inhibitor of Nogo-A in association with an attenuated downregulation of hippocampal growth-associated protein-43 expression. J Neurosurg 107:8448532007

    • Search Google Scholar
    • Export Citation
  • 61

    Marklund NFulp CTShimizu SPuri RMcMillan AStrittmatter SM: Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat. Exp Neurol 197:70832006

    • Search Google Scholar
    • Export Citation
  • 62

    McIntosh TKSaatman KERaghupathi RGraham DISmith DHLee VM: The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol 24:2512671998

    • Search Google Scholar
    • Export Citation
  • 63

    Mignone RGWeber ET: Potent inhibition of cell proliferation in the hippocampal dentate gyrus of mice by the chemotherapeutic drug thioTEPA. Brain Res 1111:26292006

    • Search Google Scholar
    • Export Citation
  • 64

    Molcanyi MRiess PBentz KMaegele MHescheler JSchafke B: Trauma-associated inflammatory response impairs embryonic stem cell survival and integration after implantation into injured rat brain. J Neurotrauma 24:6256372007

    • Search Google Scholar
    • Export Citation
  • 65

    Monje MLToda HPalmer TD: Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:176017652003

  • 66

    Morales DMMarklund NLebold DThompson HJPitkanen AMaxwell WL: Experimental models of traumatic brain injury: do we really need to build a better mousetrap?. Neuroscience 136:9719892005

    • Search Google Scholar
    • Export Citation
  • 67

    Morganti-Kossmann MCSatgunaseelan LBye NKossmann T: Modulation of immune response by head injury. Injury 38:139214002007

  • 68

    Muir JKRaghupathi RSaatman KEWilson CALee VMTrojanowski JQ: Terminally differentiated human neurons survive and integrate following transplantation into the traumatically injured rat brain. J Neurotrauma 16:4034141999

    • Search Google Scholar
    • Export Citation
  • 69

    Myckatyn TMMackinnon SEMcDonald JW: Stem cell transplantation and other novel techniques for promoting recovery from spinal cord injury. Transpl Immunol 12:3433582004

    • Search Google Scholar
    • Export Citation
  • 70

    Nunes MCRoy NSKeyoung HMGoodman RRMcKhann G IIJiang L: Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9:4394472003

    • Search Google Scholar
    • Export Citation
  • 71

    Olanow CWGoetz CGKordower JHStoessl AJSossi VBrin MF: A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 54:4034142003

    • Search Google Scholar
    • Export Citation
  • 72

    Olson AKEadie BDErnst CChristie BR: Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 16:2502602006

    • Search Google Scholar
    • Export Citation
  • 73

    Oyesiku NMEvans COHouston SDarrell RSSmith JSFulop ZL: Regional changes in the expression of neurotrophic factors and their receptors following acute traumatic brain injury in the adult rat brain. Brain Res 833:1611721999

    • Search Google Scholar
    • Export Citation
  • 74

    Parent JM: Injury-induced neurogenesis in the adult mammalian brain. Neuroscientist 9:2612722003

  • 75

    Pencea VBingaman KDFreedman LJLuskin MB: Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain. Exp Neurol 172:1162001

    • Search Google Scholar
    • Export Citation
  • 76

    Philips MFMuir JKSaatman KERaghupathi RLee VMTrojanowski JQ: Survival and integration of transplanted postmitotic human neurons following experimental brain injury in immunocompetent rats. J Neurosurg 90:1161241999

    • Search Google Scholar
    • Export Citation
  • 77

    Povlishock JTHayes RLMichel MEMcIntosh TK: Workshop on animal models of traumatic brain injury. J Neurotrauma 11:7237321994

  • 78

    Povlishock JTKatz DI: Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil 20:76942005

    • Search Google Scholar
    • Export Citation
  • 79

    Prins MLLee SMCheng CLBecker DPHovda DA: Fluid percussion brain injury in the developing and adult rat: a comparative study of mortality, morphology, intracranial pressure and mean arterial blood pressure. Brain Res Dev Brain Res 95:2722821996

    • Search Google Scholar
    • Export Citation
  • 80

    Quinones-Hinojosa ASanai NSoriano-Navarro MGonzalez-Perez OMirzadeh ZGil-Perotin S: Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol 494:4154342006

    • Search Google Scholar
    • Export Citation
  • 81

    Rabinovich SSSeledtsov VIPoveschenko OVSenuykov VVTaraban VYYarochno VI: Transplantation treatment of spinal cord injury patients. Biomed Pharmacother 57:4284332003

    • Search Google Scholar
    • Export Citation
  • 82

    Ramaswamy SGoings GESoderstrom KESzele FGKozlowski DA: Cellular proliferation and migration following a controlled cortical impact in the mouse. Brain Res 1053:38532005

    • Search Google Scholar
    • Export Citation
  • 83

    Reynolds BAWeiss S: Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:170717101992

    • Search Google Scholar
    • Export Citation
  • 84

    Rice ACKhaldi AHarvey HBSalman NJWhite FFillmore H: Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol 183:4064172003

    • Search Google Scholar
    • Export Citation
  • 85

    Richardson RMBroaddus WCHolloway KLSun DBullock MRFillmore HL: Heterotypic neuronal differentiation of adult subependymal zone neuronal progenitor cells trans planted to the adult hippocampus. Mol Cell Neurosci 28:6746822005

    • Search Google Scholar
    • Export Citation
  • 86

    Richardson RMFillmore HLHolloway KLBroaddus WC: Progress in cerebral transplantation of expanded neuronal stem cells. J Neurosurg 100:6596712004

    • Search Google Scholar
    • Export Citation
  • 87

    Richardson RMHolloway KLBullock MRBroaddus WCFillmore HL: Isolation of neuronal progenitor cells from the adult human neocortex. Acta Neurochir (Wien) 148:7737772006

    • Search Google Scholar
    • Export Citation
  • 88

    Richardson RMSun DBullock MR: Neurogenesis after traumatic brain injury. Neurosurg Clin N Am 18:169181xi2007

  • 89

    Riess PZhang CSaatman KELaurer HLLonghi LGRaghupathi R: Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery 51:104310442002

    • Search Google Scholar
    • Export Citation
  • 90

    Rose VL: NIH issues consensus statement on the rehabilitation of persons with traumatic brain injury. Am Fam Physician 59:105110531999

    • Search Google Scholar
    • Export Citation
  • 91

    Roy NSWang SJiang LKang JBenraiss AHarrison-Restelli C: In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med 6:2712772000

    • Search Google Scholar
    • Export Citation
  • 92

    Sahuquillo JPoca MAAmoros S: Current aspects of pathophysiology and cell dysfunction after severe head injury. Curr Pharm Des 7:147515032001

    • Search Google Scholar
    • Export Citation
  • 93

    Salman HGhosh PKernie SG: Subventricular zone neural stem cells remodel the brain following traumatic injury in adult mice. J Neurotrauma 21:2832922004

    • Search Google Scholar
    • Export Citation
  • 94

    Sanai NBerger MSGarcia-Verdugo JMAlvarez-Buylla A: Comment on “human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science 318:3932007

    • Search Google Scholar
    • Export Citation
  • 95

    Sanai NTramontin ADQuinones-Hinojosa ABarbaro NMGupta NKunwar S: Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:7407442004

    • Search Google Scholar
    • Export Citation
  • 96

    Sawamoto KWichterle HGonzalez-Perez OCholfin JAYamada MSpassky N: New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311:6296322006

    • Search Google Scholar
    • Export Citation
  • 97

    Schouten JWFulp CTRoyo NCSaatman KEWatson DJSnyder EY: A review and rationale for the use of cellular transplantation as a therapeutic strategy for traumatic brain injury. J Neurotrauma 21:150115382004

    • Search Google Scholar
    • Export Citation
  • 98

    Seri BGarcia-Verdugo JMMcEwen BSAlvarez-Buylla A: Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:715371602001

    • Search Google Scholar
    • Export Citation
  • 99

    Shah SAPrough DSGarcia JMDeWitt DSHellmich HL: Molecular correlates of age-specific responses to traumatic brain injury in mice. Exp Gerontol 41:120112052006

    • Search Google Scholar
    • Export Citation
  • 100

    Shear DATate MCArcher DRHoffman SWHulce VDLaplaca MC: Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. Brain Res 1026:11222004

    • Search Google Scholar
    • Export Citation
  • 101

    Shors TJMiesegaes GBeylin AZhao MRydel TGould E: Neurogenesis in the adult is involved in the formation of trace memories. Nature 410:3723762001

    • Search Google Scholar
    • Export Citation
  • 102

    Silver JMiller JH: Regeneration beyond the glial scar. Nat Rev Neurosci 5:1461562004

  • 103

    Singleton RHZhu JStone JRPovlishock JT: Traumatically induced axotomy adjacent to the soma does not result in acute neuronal death. J Neurosci 22:7918022002

    • Search Google Scholar
    • Export Citation
  • 104

    Sköld MKvon Gertten CSandberg-Nordqvist ACMathiesen THolmin S: VEGF and VEGF receptor expression after experimental brain contusion in rat. J Neurotrauma 22:3533672005

    • Search Google Scholar
    • Export Citation
  • 105

    Smith DHOkiyama KThomas MJClaussen BMcIntosh TK: Evaluation of memory dysfunction following experimental brain injury using the Morris water maze. J Neurotrauma 8:2592691991

    • Search Google Scholar
    • Export Citation
  • 106

    Smith FMRaghupathi RMacKinnon MAMcIntosh TKSaatman KEMeaney DF: TUNEL-positive staining of surface contusions after fatal head injury in man. Acta Neuropathol 100:5375452000

    • Search Google Scholar
    • Export Citation
  • 107

    Stahel PFMorganti-Kossmann MCKossmann T: The role of the complement system in traumatic brain injury. Brain Res Brain Res Rev 27:2432561998

    • Search Google Scholar
    • Export Citation
  • 108

    Sun DColello RJDaugherty WPKwon THMcGinn MJHarvey HB: Cell proliferation and neuronal differentiation in the dentate gyrus in juvenile and adult rats following traumatic brain injury. J Neurotrauma 22:951052005

    • Search Google Scholar
    • Export Citation
  • 109

    Sun DMcGinn MJZhou ZHarvey HBBullock MRColello RJ: Anatomical integration of newly generated dentate granule neurons following traumatic brain injury in adult rats and its association to cognitive recovery. Exp Neurol 204:2642722007

    • Search Google Scholar
    • Export Citation
  • 110

    Tate CCTate MCLaPlaca MC: Fibronectin and laminin increase in the mouse brain after controlled cortical impact injury. J Neurotrauma 24:2262302007

    • Search Google Scholar
    • Export Citation
  • 111

    Tate MCShear DAHoffman SWStein DGArcher DRLaPlaca MC: Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain. Cell Transplant 11:2832952002

    • Search Google Scholar
    • Export Citation
  • 112

    Tolias CMBullock MR: Critical appraisal of neuroprotection trials in head injury: what have we learned?. NeuroRx 1:71792004

  • 113

    Truettner JSchmidt-Kastner RBusto RAlonso OFLoor JYDietrich WD: Expression of brain-derived neurotrophic factor, nerve growth factor, and heat shock protein HSP70 following fluid percussion brain injury in rats. J Neurotrauma 16:4714861999

    • Search Google Scholar
    • Export Citation
  • 114

    Umile EMSandel MEAlavi ATerry CMPlotkin RC: Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability. Arch Phys Med Rehabil 83:150615132002

    • Search Google Scholar
    • Export Citation
  • 115

    Urrea CCastellanos DASagen JTsoulfas PBramlett HMDietrich WD: Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat. Restor Neurol Neurosci 25:65762007

    • Search Google Scholar
    • Export Citation
  • 116

    van Praag HSchinder AFChristie BRToni NPalmer TDGage FH: Functional neurogenesis in the adult hippocampus. Nature 415:103010342002

    • Search Google Scholar
    • Export Citation
  • 117

    Walton NMSutter BMChen HXChang LJRoper SNScheffler B: Derivation and large-scale expansion of multipotent astroglial neural progenitors from adult human brain. Development 133:367136812006

    • Search Google Scholar
    • Export Citation
  • 118

    Wang YJin KMao XOXie LBanwait SMarti HH: VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis and neuromigration. J Neurosci Res 85:7407472007

    • Search Google Scholar
    • Export Citation
  • 119

    Watson DJLonghi LLee EBFulp CTFujimoto SRoyo NC: Genetically modified NT2N human neuronal cells mediate long-term gene expression as CNS grafts in vivo and improve functional cognitive outcome following experimental traumatic brain injury. J Neuropathol Exp Neurol 62:3683802003

    • Search Google Scholar
    • Export Citation
  • 120

    Will BGalani RKelche CRosenzweig MR: Recovery from brain injury in animals: relative efficacy of environmental enrichment, physical exercise or formal training (1990–2002). Prog Neurobiol 72:1671822004

    • Search Google Scholar
    • Export Citation
  • 121

    Williams SRaghupathi RMacKinnon MAMcIntosh TKSaatman KEGraham DI: In situ DNA fragmentation occurs in white matter up to 12 months after head injury in man. Acta Neuropathol 102:5815902001

    • Search Google Scholar
    • Export Citation
  • 122

    Windrem MSRoy NSWang JNunes MBenraiss AGoodman R: Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain. J Neurosci Res 69:9669752002

    • Search Google Scholar
    • Export Citation
  • 123

    Wirth ED IIIReier PJFessler RGThompson FJUthman BBehrman A: Feasibility and safety of neural tissue transplantation in patients with syringomyelia. J Neurotrauma 18:9119292001

    • Search Google Scholar
    • Export Citation
  • 124

    Yang KPerez-Polo JRMu XSYan HQXue JJIwamoto Y: Increased expression of brain-derived neurotrophic factor but not neurotrophin-3 mRNA in rat brain after cortical impact injury. J Neurosci Res 44:1571641996

    • Search Google Scholar
    • Export Citation
  • 125

    Yoon SHShim YSPark YHChung JKNam JHKim MO: Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial. Stem Cells 25:206620732007

    • Search Google Scholar
    • Export Citation
  • 126

    Yoshimura STeramoto TWhalen MJIrizarry MCTakagi YQiu J: FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice. J Clin Invest 112:120212102003

    • Search Google Scholar
    • Export Citation
  • 127

    Zhang CLZou YHe WGage FHEvans RM: A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451:100410072008

    • Search Google Scholar
    • Export Citation
  • 128

    Zhu JWu XZhang HL: Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation. Curr Drug Targets 6:971102005

    • Search Google Scholar
    • Export Citation
  • 129

    Zhu JZhou LXingWu F: Tracking neural stem cells in patients with brain trauma. N Engl J Med 355:237623782006

  • 130

    Goldman S: Stem and progenitor cell-based therapy of the human central nervous system. Nat Biotechnol 23:8628712005

TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 351 348 40
Full Text Views 191 117 1
PDF Downloads 95 53 0
EPUB Downloads 0 0 0
PubMed
Google Scholar