Research Topics
| DOUGLAS HAMILTON SMITHSummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
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Detail Information
Publications
Development of transplantable nervous tissue constructs comprised of stretch-grown axonsBryan J Pfister
Department of Neurosurgery, Center for Brain Injury Repair, University of Pennsylvania, 3320 Smith Walk, 105 Hayden Hall, Philadelphia, PA 19104, USA
J Neurosci Methods 153:95-103. 2006..Ideally, bridging nerve damage with living axon tracts may serve to establish or promote new functional connections...- Remacemide hydrochloride reduces cortical lesion volume following brain trauma in the ratD H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104 6316, USA
Neurosci Lett 231:135-8. 1997..v. 15 min postinjury plus a subcutaneous infusion over 24 h of 20 mg/kg remacemide hydrochloride improved posttraumatic memory function determined by a Morris water maze paradigm... - Protein accumulation in traumatic brain injuryDouglas H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Neuromolecular Med 4:59-72. 2003..In addition, the potential deleterious roles of protein accumulations on functional outcome and progressive neurodegeneration following TBI will be examined... - Amyloid beta accumulation in axons after traumatic brain injury in humansDouglas H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6316, USA
J Neurosurg 98:1072-7. 2003..In the present study, the authors explored the potential relationship between Abeta accumulation in damaged axons and associated Abeta plaque formation... 
Stretch growth of integrated axon tracts: extremes and exploitationsDouglas H Smith
Center for Brain Injury and Repair, University of Pennsylvania School of Medicine, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104, USA
Prog Neurobiol 89:231-9. 2009..This review provides the first glimpse of the astonishing features of axon tracts undergoing stretch growth and how this natural process can be exploited to facilitate repair of the damaged nervous system...- Diffuse axonal injury in head traumaDouglas H Smith
Department of Neurosurgery, University of Pennsylvania, 3320 Smith Walk, 105 Hayden Hall, Philadelphia, PA 19104, USA
J Head Trauma Rehabil 18:307-16. 2003..CONCLUSIONS: Future advancements in the diagnosis and treatment of DAI will be dependent on our collective understanding of injury biomechanics, temporal axonal pathophysiology, and its role in patient outcome... - Brain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor proteinD H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104 6316, USA
Am J Pathol 153:1005-10. 1998..01). These data suggest a mechanistic link between brain trauma and Abeta levels and the death of neurons... - Roller coasters, g forces, and brain trauma: on the wrong track?Douglas H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA
J Neurotrauma 19:1117-20. 2002..Accordingly, our findings do not support the contention that current roller coaster rides produce high enough forces to mechanically deform and injure the brain... - A new strategy to produce sustained growth of central nervous system axons: continuous mechanical tensionD H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Tissue Eng 7:131-9. 2001..We propose that this newfound stretch-induced growth ability of integrated CNS axons may be exploited to produce transplant materials to bridge extensive nerve damage... - Immediate coma following inertial brain injury dependent on axonal damage in the brainstemD H Smith
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA
J Neurosurg 93:315-22. 2000..However, the relationship between the distribution of axonal damage and posttraumatic coma has not been examined. In the present study, the authors examine that relationship... 
Hemostatic and neuroprotective effects of human recombinant activated factor VII therapy after traumatic brain injury in pigsJun Zhang
Department of Neurosurgery and Penn Center for Brain Injury and Repair, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Exp Neurol 210:645-55. 2008..Finally, rFVIIa treatment provided a surprising neuroprotective effect by reducing hippocampal neuron degeneration as well as the extent of DAI...- Long-term survival and integration of transplanted engineered nervous tissue constructs promotes peripheral nerve regenerationJason H Huang
Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA
Tissue Eng Part A 15:1677-85. 2009..These findings demonstrate the promise of living tissue-engineered axonal constructs to bridge major nerve lesions and promote host regeneration, potentially by providing axon-mediated axonal outgrowth and guidance... - Harvested human neurons engineered as live nervous tissue constructs: implications for transplantation. Laboratory investigationJason H Huang
Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA
J Neurosurg 108:343-7. 2008..The authors chose to evaluate human dorsal root ganglion (DRG) neurons due to their robustness in culture... - A lack of amyloid beta plaques despite persistent accumulation of amyloid beta in axons of long-term survivors of traumatic brain injuryXiao Han Chen
Department of Neurosurgery, School of Medicine, University of Pennsylvania, 3320 Smith Walk, Philadelphia, PA 19104 6316, USA
Brain Pathol 19:214-23. 2009..These findings fail to support the premise that progressive plaque pathology after TBI ultimately results in AD... - Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy studySherman C Stein
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19106, USA
Neurosurgery 59:781-7; discussion 787-8. 2006..Recent findings have cast doubt on vasospasm as the sole cause of delayed cerebral ischemia after subarachnoid hemorrhage... - Coagulopathy in traumatic brain injurySherman C Stein
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Neurocrit Care 1:479-88. 2004..This is an area deserving of more intensive research... - Developing a tissue-engineered neural-electrical relay using encapsulated neuronal constructs on conducting polymer fibersD Kacy Cullen
Center for Brain Injury and Repair, Department of Neurosurgery, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
J Neural Eng 5:374-84. 2008.... - Biomechanics of concussionDavid F Meaney
Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 6392, USA
Clin Sports Med 30:19-31, vii. 2011..Studies of how these mechanical conditions contribute to the cellular mechanisms of damage in mild traumatic brain injury are reviewed. Finally, future directions for improving understanding concussion biomechanics are discussed... - Dendritic alterations after dynamic axonal stretch injury in vitroHubert Monnerie
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19107, USA
Exp Neurol 224:415-23. 2010..The data also imply that TAI may alter dendrite structure and plasticity in vivo. An understanding of TAI's effect on dendrites is important since proper dendrite function is crucial for normal brain function and recovery after injury... - Signaling, delivery and age as emerging issues in the benefit/risk ratio outcome of tPA For treatment of CNS ischemic disordersWilliam M Armstead
Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurochem 113:303-12. 2010..Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals... - Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in miceKathryn E Saatman
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA
J Cereb Blood Flow Metab 23:34-42. 2003..These data suggest that early calpain activation may contribute to progressive intraaxonal structural damage, whereas delayed calpain activation may be associated with axonal degeneration... - Red blood cells-coupled tPA prevents impairment of cerebral vasodilatory responses and tissue injury in pediatric cerebral hypoxia/ischemia through inhibition of ERK MAPK activationWilliam M Armstead
Department of Anesthesiology and Critical Care, 3620 Hamilton Walk, JM3, University of Pennsylvania, Philadelphia, PA l9l04, USA
J Cereb Blood Flow Metab 29:1463-74. 2009..These data suggest that coupling of tPA to RBCs offers a novel approach toward increasing the benefit/risk ratio of thrombolytic therapy for CNS disorders associated with H/I... - Erythrocyte-bound tissue plasminogen activator is neuroprotective in experimental traumatic brain injurySherman C Stein
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19106, USA
J Neurotrauma 26:1585-92. 2009..01) and hippocampal cell loss ( p<0.01) in the RBC=tPA group than in all other groups. These results reveal that RBC/tPA is more neuroprotective in experimental TBI than is unbound tPA... - Association between intravascular microthrombosis and cerebral ischemia in traumatic brain injurySherman C Stein
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Neurosurgery 54:687-91; discussion 691. 2004..CONCLUSION: These data support a strong link between intravascular microthrombosis and neuronal death after brain trauma in humans and may have important implications for new therapeutic approaches... - Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain traumaXiao-Han Chen
Department of Neurosurgery, University of Pennsylvania, 105C Hayden Hall, 3320 SmithWalk, Philadelphia, PA 19104-6316, USA
Am J Pathol 165:357-71. 2004..The abnormal concentration of these factors may lead to APP proteolysis and Abeta formation within the axonal membrane compartment... - Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in ratsKevin D Browne
Department of Neurosurgery, Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia, PA 19104, USA
Exp Neurol 201:301-7. 2006..These data may have important implications for TBI patients who are often prescribed NSAIDs for chronic pain... - Neutralizing the neurotoxic effects of exogenous and endogenous tPAWilliam M Armstead
Department of Anesthesiology, University of Pennsylvania, 3620 Hamilton Walk, JM3, Philadelphia, Pennsylvania 19104, USA
Nat Neurosci 9:1150-5. 2006..These experiments suggest mechanisms to reduce the neurotoxic effects of tPA without compromising its fibrinolytic activity, through the use of selective antagonists and new tPA formulations... - Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitorsAkira Iwata
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6316, USA
J Neurosci 24:4605-13. 2004..In turn, degradation of the alpha-subunit promotes persistent elevations in [Ca2+]i, fueling additional pathologic changes. These observations may have important implications for developing therapeutic strategies for axonal trauma... - Effect of acute calcium influx after mechanical stretch injury in vitro on the viability of hippocampal neuronsTheresa A Lusardi
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
J Neurotrauma 21:61-72. 2004.... - Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injurySherman C Stein
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Neurosurg 97:1373-7. 2002..CONCLUSIONS: These results strongly support the contention that IC is a universal response to TBI and an important secondary cerebral insult... - Acute treatment with MgSO4 attenuates long-term hippocampal tissue loss after brain trauma in the ratKevin D Browne
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurosci Res 77:878-83. 2004..These data also show that the previously reported broad efficacy of MgSO(4) or NPS 1506 observed shortly after brain trauma could not be detected 8 months post-injury... - Extreme stretch growth of integrated axonsBryan J Pfister
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurosci 24:7978-83. 2004..These data provide the first evidence that mechanical stimuli can induce extreme "stretch growth" of integrated axon tracts, far exceeding any previously observed limits of axon growth... - A device to study the initiation and propagation of calcium transients in cultured neurons after mechanical stretchTheresa A Lusardi
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6392, USA
Ann Biomed Eng 32:1546-58. 2004.... - Long-term survival and outgrowth of mechanically engineered nervous tissue constructs implanted into spinal cord lesionsAkira Iwata
Department of Neurosurgery, Center for Brain Injury Repair, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Tissue Eng 12:101-10. 2006..These results demonstrate the promise of nervous tissue constructs consisting of stretch-grown axons to bridge even extensive spinal cord lesions... - Long-term accumulation of amyloid-beta in axons following brain trauma without persistent upregulation of amyloid precursor protein genesAkira Iwata
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6316, USA
J Neuropathol Exp Neurol 61:1056-68. 2002..Together, these data suggest a mechanism that may contribute to long-term neurodegeneration following brain trauma... - Sodium channelopathy induced by mild axonal trauma worsens outcome after a repeat injuryTracy J Yuen
Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6316, USA
J Neurosci Res 87:3620-5. 2009..These data suggest that mild TAI induces a form of sodium channelopathy on axons that greatly exaggerates the pathophysiologic response to subsequent mild injuries... - The separate roles of calcium and mechanical forces in mediating cell death in mechanically injured neuronsTheresa A Lusardi
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6392, USA
Biorheology 40:401-9. 2003..Finally, at the highest levels of stretch, the cell survivability decreases at 24 hrs following the stretch injury. These data show the association between loss in calcium regulation and early signs of neuronal cell death... - Traumatic brain injury induces biphasic upregulation of ApoE and ApoJ protein in ratsAkira Iwata
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6316, USA
J Neurosci Res 82:103-14. 2005..Collectively, these data suggest that ApoE and J play a role in the acute sequelae of brain trauma and reemerge long after the initial insult, potentially to modulate progressive neurodegenerative changes... - Mechanical breaking of microtubules in axons during dynamic stretch injury underlies delayed elasticity, microtubule disassembly, and axon degenerationMin D Tang-Schomer
Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
FASEB J 24:1401-10. 2010..While the disintegration of microtubules allows delayed recovery of the "normal" straight axon morphology, it comes at a great cost by interrupting axonal transport, leading to axonal swelling and degeneration... - Apo E genotype not associated with intravascular coagulation in traumatic brain injurySherman C Stein
Department of Neurosurgery, University of Pennsylvania, 105B Hayden Hall/3320 Smith Walk, Philadelphia, PA 19104-6316, USA
Neurosci Lett 387:28-31. 2005..The authors explored a possible connection between the apolipoprotein E (Apo E) genotype, coagulopathy and intravascular microthombosis (IMT) in TBI. The predicted association was not confirmed... - Neurogenesis and glial proliferation persist for at least one year in the subventricular zone following brain trauma in ratsXiao-Han Chen
Department of Neurosurgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
J Neurotrauma 20:623-31. 2003..These data suggest that there is a persistent proliferation of neurons and glia in the SVZ following brain trauma that does not diminish during aging as found in non-injured animals... - Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunitCatherine R von Reyn
Departments of Bioengineering, Pharmacology, Neurosurgery, Emergency Medicine, and Neuroscience, University of Pennsylvania, Philadelphia, PA 19104 6321, USA
J Neurosci 29:10350-6. 2009.... - In-vitro approaches for studying blast-induced traumatic brain injuryYung Chia Chen
Departments of Bioengineering, University of Pennsylvania, 210 S 33rd Street, Philadelphia, PA 19104, USA
J Neurotrauma 26:861-76. 2009..These in-vitro models, viewed in combination with in-vivo models and clinical studies, can be used to assess both the mechanisms and possible treatments for this type of trauma... - A neprilysin polymorphism and amyloid-beta plaques after traumatic brain injuryVictoria E Johnson
Penn Center for Brain Injury and Repair, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurotrauma 26:1197-202. 2009..Moreover, these findings provide a potential genetic screening test for individuals at high risk of TBI, such as participants in contact sports and military personnel... - A novel neuroprosthetic interface with the peripheral nervous system using artificially engineered axonal tractsNiranjan Kameswaran
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
Neurol Res 30:1063-7. 2008.... - Stretch-grown axons retain the ability to transmit active electrical signalsBryan J Pfister
Department of Biomedical Engineering, New Jersey Institute of Technology, Philadelphia, PA 19104, USA
FEBS Lett 580:3525-31. 2006..Surprisingly, Na and K channel density increased due to stretch-growth, which may represent a natural response to preserve the fidelity of neuronal signaling... - Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humansKunihiro Uryu
The Center for Neurodegenerative Disease Research, Pathology and Laboratory Medicine, USA
Exp Neurol 208:185-92. 2007..This process may have important implications for survivors of TBI who have been shown to be at greater risk of developing neurodegenerative diseases... - Neural engineering to produce in vitro nerve constructs and neurointerfaceBryan J Pfister
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, USA
Neurosurgery 60:137-41; discussion 141-2. 2007..In this article, we describe how this novel neural engineering approach may be used to produce a nervous tissue interface to integrate disconnected motor and sensory functions for external control... - Spatiotemporal distribution of spectrin breakdown products induced by anoxia in adult rat optic nerve in vitroNathalie Jette
Ottawa Health Research Institute, Division of Neuroscience, University of Ottawa, Ottawa, Ontario, Canada
J Cereb Blood Flow Metab 26:777-86. 2006..Thus, proteolysis of structural and functional proteins will conspire to irreversibly injure central axons and render them nonfunctional, eventually leading to transection, degradation, and Wallerian degeneration... - Thalamic nuclei after human blunt head injuryWilliam L Maxwell
Department of Anatomy, Division of Neuroscience and Biomedical Systems, University of Glasgow, UK
J Neuropathol Exp Neurol 65:478-88. 2006..The study provides novel quantitative evidence for differential neuronal loss, with survival after human head injury, from thalamic nuclei associated with different aspects of cortical activation...
Research Grants
- BRAIN INJURY EFFECTS--AGE RELATED COGNITIVE DYSFUNCTIONDouglas Smith; Fiscal Year: 1999..4) To evaluate the therapeutic efficacy of cognition enhancers on persisting post traumatic cognitive dysfunction in young and aging rats. ..
- BRAIN INJURY, AGING AND NEURODEGENERATION IN THE RATDouglas Smith; Fiscal Year: 2004..Success of these studies may reveal mechanistic links between brain trauma, age and neurodegenerative processes and provide a basis for the development of new therapeutic strategies. ..
- Pathophysiology of Traumatic Axonal InjuryDouglas Smith; Fiscal Year: 2007..Collectively, our proposed studies may improve understanding of potential mediators of secondary injury shortly following DAI and provide insight into progressive pathologies induced by brain trauma. ..
- Pathophysiology of Traumatic Axonal InjuryDouglas Smith; Fiscal Year: 2007..Collectively, our proposed studies may improve understanding of potential mediators of secondary injury shortly following DAI and provide insight into progressive pathologies induced by brain trauma. ..
- TBI: Uncovering Mechanisms of AD-like pathologyDOUGLAS HAMILTON SMITH; Fiscal Year: 2010..Here, we propose to examine how TBI may be transformed into a progressive neurodegenerative disease with pathologic features resembling AD. ..
- Spinal cord repair with nerve constructsDouglas Smith; Fiscal Year: 2007....
- Spinal cord repair with nerve constructsDouglas Smith; Fiscal Year: 2009..abstract_text> ..
- LONG TERM EFFECTS OF DIFFUSE BRAIN TRAUMADouglas Smith; Fiscal Year: 2002..Success of these studies may reveal mechanistic links between brain trauma and neurodegenerative processes and facilitate the development of therapeutic and diagnostic techniques for diffuse brain injury. ..