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2. Comparison of Perioperative Morbidity in Translaminar Facet Versus Pedicle Screw Fixation

Author

Sagun Tuli, Marc E. Eichler, and Eric J. Woodard

Subjects
Adult, Male, musculoskeletal diseases, Sacrum, medicine.medical_specialty, Bone Screws, Fixation (surgical), Lumbar, medicine, Humans, Orthopedics and Sports Medicine, Pedicle screw fixation, Retrospective Studies, Lumbar Vertebrae, business.industry, Retrospective cohort study, Perioperative, Middle Aged, musculoskeletal system, Surgery, Spinal Fusion, Treatment Outcome, Orthopedic surgery, Female, business, Lumbosacral joint
Abstract

This retrospective study evaluated the perioperative morbidity of patients undergoing lumbar, sacral, or lumbosacral fusion using either pedicle or translaminar facet screw fixation following interbody fusion. Hospital charts of all patients who presented to a single tertiary care institution during a 4-year period were reviewed. Findings indicated translaminar facet screw fixation was a less invasive spinal fixation method with decreased perioperative morbidity compared to pedicle screw fixation.

Published
2005
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3. Reliability of Radiologic Assessment of Fusion: Cervical Fibular Allograft Model

Author

Peng R Chen, Sagun Tuli, Marc E. Eichler, and Eric J. Woodard

Subjects
Male, medicine.medical_specialty, Bone Regeneration, Radiography, medicine.medical_treatment, Spinal Osteophytosis, Cohen's kappa, Osteogenesis, Predictive Value of Tests, medicine, Cervical spondylosis, Humans, Transplantation, Homologous, Orthopedics and Sports Medicine, Prospective Studies, Corpectomy, Reliability (statistics), Statistic, Observer Variation, Fusion, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, Confidence interval, Surgery, Spinal Fusion, Cervical Vertebrae, Female, Neurology (clinical), Radiology, business
Abstract

STUDY DESIGN Prospective assessment of the reliability of determining cervical fusion success based on plain radiographs. OBJECTIVES Determination of the reliability of plain static radiographs in predicting the presence or absence of fusion. SUMMARY OF BACKGROUND DATA The ability of plain radiographs to assess the presence of fusion is limited. In addition, variations in the definition of "fusion" make this entity an important aspect for study. METHODS A study was carried out to determine the reliability of plain radiographs in predicting bony fusion. Cases of cervical spondylosis undergoing a single or multilevel corpectomy with an allograft fusion and anterior instrumentation were chosen for the model. The definition of "bony fusion" was obtained from the literature. Bony fusion was defined by the presence of bony trabeculation across the graft-host interfaces, the assessment of the change in strut height over time, and the development of a kyphotic angulation over time. Data were collected at a tertiary care institution over a 5-year period. Descriptive statistics regarding baseline patient characteristics, the underlying disease process, and the surgical intervention, were obtained. Reliability of plain static radiographs in assessing fusion was evaluated by two independent neuroradiologists blinded to any subsequent clinical outcome. The Cohen Kappa statistic was used to determine the degree of agreement regarding the presence or absence of fusion at the superior and inferior aspect of the graft at the 6-week and the 12-week follow-up. RESULTS The study involved 57 patients (30 males and 27 females), with a median age of 49 years. The number of levels decompressed was 1, 2, and 3 in 36, 20, and 1 patients, respectively. Fourteen patients had a history of smoking. The Cohen Kappa statistic revealed variable results depending on the time period and aspect evaluated. The degree of agreement at 6 weeks was 0.61 (95% confidence interval = 0.32-0.89) and 0.44 (95% confidence interval = 0.017-0.86) and at 12 weeks was 0.18 (95% confidence interval = -0.21-0.58) and 1.00 for the superior and inferior aspect of the graft, respectively. CONCLUSIONS Plain radiographs are generally quite unreliable in predicting fusion based on presence or absence of trabeculation.

Published
2004
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4. Intracellular Calcium Levels Influence Apoptosis in Mature Sensory Neurons after Trophic Factor Deprivation

Author

Marc E. Eichler, Keith M. Rich, and Jianxin X. Tong

Subjects
Programmed cell death, Cell Survival, chemistry.chemical_element, Apoptosis, Calcium, Biology, Calcium in biology, Rats, Sprague-Dawley, Developmental Neuroscience, Dorsal root ganglion, Ganglia, Spinal, medicine, Animals, Nerve Growth Factors, Cells, Cultured, Sensory neuron, Rats, Cell biology, medicine.anatomical_structure, Nerve growth factor, nervous system, Neurology, chemistry, Cell culture, Immunology, Intracellular, DNA Damage
Abstract

Embryonic dorsal root ganglion (DRG) neurons require nerve growth factor (NGF) for survival in vitro. Withdrawal of NGF results in an apoptotic death in these immature DRG neurons. After time in culture, DRG neurons become progressively less dependent upon NGF for survival. Immature embryonic DRG neurons remain highly dependent upon NGF during their first 14 days in cell culture but by Day 21 the majority lose their NGF dependence for survival. During this period of maturation the intracellular calcium concentration ([Ca2+]i) progressively increases from the lower levels found in immature DRG neurons to the higher levels that are characteristic of older or mature DRG neurons. By changing the cell culture medium to one with very low calcium, we were able to lower [Ca2+]i in the mature neurons to levels similar to those found in immature neurons. These mature neurons (e.g., E-15 DRG neurons grown for 21 days in culture), normally NGF independent, became highly dependent upon NGF for survival. The onset of DNA fragmentation is a marker of apoptotic cell death. We measured the onset of DNA fragmentation in apoptotic neurons with use of the fluorescent dye, Hoechst, in neurons maintained in either standard calcium medium (1800 mM) or in the low calcium medium (0.35 mM). A higher percentage of neurons with lowered [Ca2+]i showed initial signs of apoptosis, i.e., DNA condensation, at earlier times after NGF deprivation. This work provides further evidence to support a "set-point" hypothesis regarding the relationship between intracellular calcium concentration and NGF dependence for survival in DRG neurons.

Published
1996
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5. Endoscopic transventricular hippocampectomy

Author

Daniel L. Silbergeld, Vrijesh S. Tantuwaya, Dennis G. Vollmer, and Marc E. Eichler

Subjects
medicine.medical_specialty, General Neuroscience, Middle temporal gyrus, Transventricular, Hippocampus, Collateral eminence, Anatomy, Surgery, Temporal lobe, Calcar avis, nervous system, medicine, Trigone of urinary bladder, Epilepsy surgery, Neurology (clinical), Psychology
Abstract

Several different types of resections are performed for medically intractable mesiobasal temporal lobe epilepsy (TLE). Although the amount of neocortical and amygdalar resection varies, most surgeons agree that removal of at least a portion of the hippocampus is critical for seizure control. We describe a preliminary cadaveric investigation of the feasibility of endoscopic hippocampectomy. A transsquamosal approach through the middle temporal gyrus permitted easy access to the pes hippocampus through the temporal horn of the lateral ventricle but made access to the body and tail of the hippocampus difficult. A posterior approach, through the occipital horn of the lateral ventricle, as in placement of an occipital ventricular catheter, permitted a clearer view of the entire hippocampus from the trigone to the pes hippocampus. Using this technique, we identified the choroid plexus and fissure, calcar avis, collateral trigone, collateral eminence, and uncal recess of the temporal horn. Transventricular endoscopy, through an occipital approach to the temporal horn, permits clear visualization of the pertinent intraventricular anatomy necessary to perform a hippocampectomy. With further developments in neuroendoscopic technology, this approach may provide a surgical strategy for patients with medically intractable epilepsy of well-defined mesiobasal origin.

Published
1995
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7. Contributors

Author

Bizhan Aarabi, Rick Abbott, Saleem I. Abdulrauf, Frank L. Acosta, John R. Adler, Nzhde Agazaryan, Manish Aghi, Edward S. Ahn, Ali Alaraj, Gregory W. Albert, Leland Albright, Felipe C. Albuquerque, Tord D. Alden, Michael J. Alexander, Andrei V. Alexandrov, Ossama Al-Mefty, Ron L. Alterman, Lázaro Álvarez, Nduka M. Amankulor, Peter S. Amenta, Christopher P. Ames, Sepideh Amin-Hanjani, Mario Ammirati, Carryn Anderson, Richard C.E. Anderson, William S. Anderson, Peter D. Angevine, Hiba Arif, Jeffrey E. Arle, Rocco Armonda, Paul M. Arnold, Kaveh Asadi-Moghaddam, Ferhan A. Asghar, William W. Ashley, Sabri Aydin, Nafi Aygun, Joachim M. Baehring, Jacob H. Bagley, Diaa Bahgat, Julian E. Bailes, Jonathon R. Ball, Gordon H. Baltuch, Nicholas C. Bambakidis, Scott C. Baraban, Igor J. Barani, Nicholas M. Barbaro, Frederick G. Barker, Gene H. Barnett, Stanley L. Barnwell, Constance M. Barone, Daniel L. Barrow, Fabrice Bartolomei, Juan Bartolomei, Tracy T. Batchelor, H. Hunt Batjer, Andrew M. Bauer, Joel A. Bauman, Thomas K. Baumann, James E. Baumgartner, John Bayouth, Andrew Beaumont, Joshua B. Bederson, Rudolf Beisse, Randy S. Bell, Allan Belzberg, Alim Louis Benabid, Eduardo E. Benarroch, Abdelhamid Benazzouz, Bernard R. Bendok, Edward C. Benzel, Alejandro Berenstein, Mitchel S. Berger, Marvin Bergsneider, Helmut Bertalanffy, Tarun Bhalla, Dani S. Bidros, José Biller, Mark H. Bilsky, Devin K. Binder, William Bingaman, Rolfe Birch, Allen T. Bishop, Peter M. Black, Jeffrey P. Blount, Peter C. Blumbergs, Leif-Erik Bohman, Zackary E. Boomsaad, Frederick A. Boop, Pascal Bou-Haidar, Daniel R. Boué, Blaise F.D. Bourgeois, Robin M. Bowman, Oliver Bozinov, Helen M. Bramlett, Henry Brem, Steven Brem, Gavin W. Britz, Douglas L. Brockmeyer, David J. Brooks, Samuel R. Browd, Paul D. Brown, Robert D. Brown, Jeffrey N. Bruce, Janice E. Brunstrom-Hernandez, John Buatti, M. Ross Bullock, Kim J. Burchiel, Peter C. Burger, Marc R. Bussière, Mohamad Bydon, Richard W. Byrne, Maria Elisa Calcagnotto, Victoria A. Campbell, William Campbell, George M. Cannon, Louis P. Caragine, Benjamin S. Carson, Gregory D. Cascino, Ethan Cascio, Frédéric Castinetti, C. Michael Cawley, Justin S. Cetas, Stéphan Chabardès, Edward F. Chang, Eric C. Chang, Eric L. Chang, Steven D. Chang, Steven W. Chang, Susan M. Chang, Kevin Chao, Paul H. Chapman, Fady T. Charbel, Patrick Chauvel, Grace Chen, Boyle C. Cheng, Joseph S. Cheng, Joshua J. Chern, E. Antonio Chiocca, Ondrej Choutka, Shakeel A. Chowdhry, Cindy W. Christian, Kathy Chuang, Jan Claassen, Richard E. Clatterbuck, Elizabeth B. Claus, Daniel R. Cleary, Robert J. Coffey, Alan R. Cohen, Andrew J. Cole, E. Sander Connolly, Patrick J. Connolly, Anne G. Copay, Jeroen R. Coppens, James J. Corbett, Daniel M. Corcos, Domagoj Coric, Garth Rees Cosgrove, William T. Couldwell, Stirling Craig, Neil R. Crawford, Peter B. Crino, R. Webster Crowley, Bradford A. Curt, Marek Czosnyka, Zofia Czosnyka, Vladimir Y. Dadashev, Andrew T. Dailey, Deepa Danan, Shabbar F. Danish, Shervin R. Dashti, Carlos A. David, David J. David, Arthur L. Day, Antonio A.F. De Salles, Amir R. Dehdashti, Oscar H. Del Brutto, Johnny B. Delashaw, Bradley Delman, Mahlon R. DeLong, Franco DeMonte, Sanjay S. Dhall, Mark S. Dias, Curtis A. Dickman, W. Dalton Dietrich, Michael L. DiLuna, Francesco Di Meco, Peter Dirks, C. Edward Dixon, Jacob A. Donoghue, Ian G. Dorward, Amish H. Doshi, James Drake, Dan Drzymalski, Rose Du, Andrew Ducruet, Ann-Christine Duhaime, Aaron S. Dumont, Christopher D. Duntsch, Joshua R. Dusick, Suzan Dyve, James Eberwine, Paula Eboli, Robert D. Ecker, Richard J. Edwards, Marc E. Eichler, Doortje C. Engel, Nancy E. Epstein, Matthew G. Ewend, Hamad Farhat, Christopher J. Farrell, Michael G. Fehlings, Iman Feiz-Erfan, Neil A. Feldstein, Richard G. Fessler, Juan J. Figueroa, Aaron G. Filler, J. Max Findlay, Michael A. Finn, David J. Fiorella, James L. Fisher, Robert S. Fisher, Eugene S. Flamm, James D. Fleck, Kelly D. Flemming, John C. Flickinger, Laura Flores-Sarnat, Kenneth A. Follett, Kelly D. Foote, Daryl R. Fourney, Valerie Fraix, James L. Frazier, Itzhak Fried, Allan H. Friedman, William A. Friedman, Gerhard M. Friehs, Donald E. Fry, Gregory N. Fuller, Hector H. Garcia, Paul A. Gardner, Mark Garrett, Hugh Garton, Cormac G. Gavin, Alisa D. Gean, Thomas A. Gennarelli, Venelin Gerganov, Anand V. Germanwala, Massimo Gerosa, Elizabeth R. Gerstner, Peter C. Gerszten, Saadi Ghatan, Samer Ghostine, Steven Giannotta, Paul R. Gigante, Frank Gilliam, Holly Gilmer-Hill, Albert Gjedde, Roberta P. Glick, Ziya L. Gokaslan, Yakov Gologorsky, Kiarash Golshani, Nestor R. Gonzalez, James Tait Goodrich, Tessa Gordon, Alessandra A. Gorgulho, Liliana C. Goumnerova, M. Sean Grady, Jordan Grafman, Sylvie Grand, Gerald A. Grant, Gregory P. Graziano, Benjamin Greenberg, James Guest, Abhijit Guha, Murat Günel, Gaurav Gupta, Nalin Gupta, Jorge Guridi, Barton L. Guthrie, Georges F. Haddad, Michael M. Haglund, Regis W. Haid, Stephen J. Haines, Clement Hamani, Bronwyn E. Hamilton, D. Kojo Hamilton, Todd C. Hankinson, Leo T. Happel, Ihtsham Ul Haq, Raqeeb Haque, Robert E. Harbaugh, Ciara D. Harraher, Leo Harris, James S. Harrop, Wael Hassaneen, Cynthia Hawkins, Gregory W.J. Hawryluk, Neal G. Haynes, Robert F. Heary, Amy B. Heimberger, Mary M. Heinricher, Thomas M. Hemmen, Jaimie M. Henderson, Roberto C. Heros, Karl Herrup, Shawn L. Hervey-Jumper, Gregory G. Heuer, Lawrence J. Hirsch, Robert Hirschl, Brian L. Hoh, Daniel J. Hoh, Eric C. Holland, Paul E. Holtzheimer, L. Nelson Hopkins, Philip J. Horner, David A. Hovda, Matthew A. Howard, Patrick Hsieh, Yin C. Hu, Sherwin E. Hua, Jason H. Huang, Judy Huang, Samuel A. Hughes, Thierry A.G.M. Huisman, Matthew A. Hunt, R. John Hurlbert, Robert W. Hurst, Anita Huttner, Steven W. Hwang, Ioannis U. Isaias, Bermans J. Iskandar, Arun Jacob, Kurt A. Jaeckle, Jay Jagannathan, Regina I. Jakacki, George I. Jallo, John A. Jane, Ryan Janicki, Damir Janigro, N u Owase Jeelani, Kurt A. Jellinger, Arthur L. Jenkins, Sarah Jernigan, David F. Jimenez, Conrad E. Johanson, J. Patrick Johnson, Matthew D. Johnson, G. Alexander Jones, Rajni K. Jutla, Koijan Singh Kainth, Michael G. Kaiser, U. Kumar Kakarla, Iain H. Kalfas, Aleksandrs Uldis Kalnins, Hideyuki Kano, Yucel Kanpolat, Adam S. Kanter, Reza J. Karimi, Amin B. Kassam, Bruce A. Kaufman, Christian B. Kaufman, Hiroto Kawasaki, Brian C. Kelley, Christopher P. Kellner, Nicole C. Keong, John R.W. Kestle, Alexander A. Khalessi, Nadia Khan, Vini G. Khurana, Daniel H. Kim, Dong Gyu Kim, Dong H. Kim, Jong Hyun Kim, Louis J. Kim, Paul K. Kim, Thomas Aquinas Kim, Won Kim, James A.J. King, Ryan S. Kitagawa, Neil D. Kitchen, Paul Klimo, David G. Kline, Kazutaka Kobayashi, Patrick M. Kochanek, Douglas Kondziolka, Paul N. Kongkham, Tyler R. Koski, Thomas Kosztowski, Paul Krack, Joachim K. Krauss, Michael A. Kraut, Niklaus Krayenbühl, Thomas Kretschmer, Ajit Krishnaney, Charles Kuntz, Jeffrey V. Kuo, Brian K. Kwon, Nadia N. Issa Laack, Shivanand P. Lad, Alim M. Ladha, Amos K. Ladouceur, Arthur M. Lam, Frederick F. Lang, Giuseppe Lanzino, Sean D. Lavine, Edward R. Laws, Michael T. Lawton, Adrian W. Laxton, Tuong H. Le, Jean François LeBas, Brett D. Lebed, Richard L. Lebow, Amy Lee, Ian Lee, Seon-Kyu Lee, Emily Lehmann, James W. Leiphart, Gregory P. Lekovic, Frederick A. Lenz, Jeffrey R. Leonard, Peter D. LeRoux, Marc Lévêque, Allan D. Levi, Elad I. Levy, Linda M. Liau, Jason Liauw, Roger Lichtenbaum, Terry Lichtor, David D. Limbrick, Hester Lingsma, Michael J. Link, Mark E. Linskey, Brian Litt, Zachary N. Litvack, James K.C. Liu, Kenneth C. Liu, Jay S. Loeffler, Christopher M. Loftus, Russell R. Lonser, Angeliki Louvi, Andres M. Lozano, Daniel C. Lu, Rimas V. Lukas, L. Dade Lunsford, Neal Luther, Pedro Lylyk, Andrew I.R. Maas, R. Loch Macdonald, Andre Machado, Raul Macias, Robert J. Maciunas, Brian N. Maddux, Pierre Magistretti, Martijn J.A. Malessy, Neil R. Malhotra, Donald A. Malone, Adam N. Mamelak, Christopher E. Mandigo, Francesco T. Mangano, Allen H. Maniker, Geoffrey T. Manley, Daniel Marchac, Anthony Marmarou, Joseph C. Maroon, Lawrence F. Marshall, Neil A. Martin, Timothy J. Martin, Alexander M. Mason, Marlon S. Mathews, Helen S. Mayberg, James P. McAllister, J. Gordon McComb, Paul C. McCormick, Ian E. McCutcheon, Michael W. McDermott, Cameron G. McDougall, Matthew McGehee, Cameron C. McIntyre, Guy M. McKhann, M. Sean McKisic, David F. Meaney, Minesh P. Mehta, Vivek Mehta, William P. Melega, Arnold H. Menezes, Patrick Mertens, Fredric B. Meyer, Scott A. Meyer, Philip M. Meyers, Costas Michaelides, Karine Michaud, Rajiv Midha, Vincent J. Miele, Jonathan Miller, Matthew L. Miller, Neil R. Miller, John Mitrofanis, Kevin Y. Miyashiro, J. Mocco, Michael T. Modic, Parham Moftakhar, Avinash Mohan, Stephen J. Monteith, Jacques J. Morcos, Michael Morgan, David E. Morris, S. David Moss, J. Paul Muizelaar, Karim Mukhida, Praveen V. Mummaneni, Gregory J.A. Murad, Karin Muraszko, Antônio C.M. Mussi, Imad Najm, Peter Nakaji, Sandra Narayanan, David W. Newell, M. Kelly Nicholas, Yasunari Niimi, Shahid M. Nimjee, Ajay Niranjan, Richard B. North, Josef Novotny, Turo Nurmikko, Samuel E. Nutt, W. Jerry Oakes, José A. Obeso, Alfred T. Ogden, Lissa Ogieglo, Christopher S. Ogilvy, David O. Okonkwo, Michael S. Okun, Edward H. Oldfield, Alessandro Olivi, Stephen E. Olvey, David Omahen, Brent O'Neill, Rod J. Oskouian, Robert Owen, Koray Özduman, Ali Kemal Ozturk, M. Necmettin Pamir, Dachling Pang, Jamie Pardini, Andrew D. Parent, T.S. Park, Michael D. Partington, Aman B. Patel, Parag G. Patil, Nicola Pavese, Richard D. Penn, Noel I. Perin, John A. Persing, Erika A. Petersen, Anthony L. Petraglia, Brigitte Piallat, Joseph H. Piatt, John D. Pickard, Joseph M. Piepmeier, Webster H. Pilcher, José Pineda, Joseph D. Pinter, Mary L. Pisculli, Thomas Pittman, Ian F. Pollack, Pierre Pollak, Bruce E. Pollock, Francisco A. Ponce, Alyx B. Porter, Randall W. Porter, Kalmon D. Post, Alexander K. Powers, Mark R. Proctor, Robert W. Prost, Jeffrey Pugh, Alfredo Quiñones-Hinojosa, Corey Raffel, Sharad Rajpal, Leonardo Rangel-Castilla, Ganesh Rao, Ahmed Raslan, Peter A. Rasmussen, Dibyendu K. Ray, Shaan M. Raza, Davis L. Reames, Chandan G. Reddy, Andy J. Redmond, Jean Régis, Peter L. Reilly, Dominique Renier, Daniel K. Resnick, Renee Reynolds, Ali R. Rezai, Laurence D. Rhines, Albert L. Rhoton, Teresa Ribalta, R. Mark Richardson, Daniele Rigamonti, Gregory J. Riggins, Jay Riva-Cambrin, Paolo Rizzo, David W. Roberts, Claudia Robertson, Lawrence Robinson, Shenandoah Robinson, Pierre-Hugues Roche, Mark A. Rockoff, Gerald E. Rodts, Pantaleo Romanelli, Mark L. Rosenblum, Joshua M. Rosenow, Michael K. Rosner, Eric S. Rovner, Christina L. Runge-Samuelson, Stephen M. Russell, James T. Rutka, Oren Sagher, Eric G. St. Clair, Madjid Samii, Prakash Sampath, Srinath Samudrala, Nader Sanai, Robert A. Sanford, Paul Santiago, Teresa Santiago-Sim, Harvey B. Sarnat, Raymond Sawaya, W. Michael Scheld, Wouter I. Shirzadi, Nicholas D. Schiff, Clemens M. Schirmer, David Schlesinger, Meic H. Schmidt, Joost W. Schouten, Johannes Schramm, Thomas C. Schuler, James M. Schuster, Theodore H. Schwartz, Judith A. Schwartzbaum, Patrick M. Schweder, R. Michael Scott, Eric Seigneuret, Nathan R. Selden, Warren R. Selman, Christopher I. Shaffrey, Manish N. Shah, Kiarash Shahlaie, William R. Shapiro, Deepak Sharma, Jason P. Sheehan, Jonas M. Sheehan, Arun K. Sherma, James M. Shiflett, Helen A. Shih, Jay L. Shils, Alexander Y. Shin, Ali Shirzadi, Adnan H. Siddiqui, Marc Sindou, Konstantin V. Slavin, Edward R. Smith, Justin S. Smith, Yoland Smith, Matthew D. Smyth, Penny K. Sneed, Brian J. Snyder, Kenneth V. Snyder, Robert A. Solomon, Volker K.H. Sonntag, Leif Sørensen, Sulpicio G. Soriano, Mark M. Souweidane, Julian Spears, David Spencer, Dennis D. Spencer, Robert F. Spetzler, Robert J. Spinner, Brett R. Stacey, William C. Stacey, Robert M. Starke, Philip A. Starr, Gary K. Steinberg, Frederick L. Stephens, Barney J. Stern, Charles B. Stevenson, Eric Stiner, Scellig Stone, Nicole L. Stroud, Robert Morgan Stuart, Brian R. Subach, Patrick A. Sugrue, Dima Suki, Wale A.R. Sulaiman, Daniel L. Surdell, William W. Sutherling, Leslie N. Sutton, Omar N. Syed, Michele Tagliati, Yasushi Takagi, Rafael J. Tamargo, Caroline C. Tan, Nitin Tandon, Marcos Tatagiba, Michael D. Taylor, Steven A. Telian, Charles Teo, Jeffrey M. Tessier, Khoi D. Than, Kamal Thapar, Nicholas Theodore, B. Gregory Thompson, Robert Tiel, Tarik Tihan, Ann Tilton, Shelly D. Timmons, Maria Toledo, Tadanori Tomita, Nestor D. Tomycz, Napoleon Torres, Charles P. Toussaint, Bruce D. Trapp, Vincent C. Traynelis, R. Shane Tubbs, Luis M. Tumialán, Allan R. Tunkel, Atsushi Umemura, Alexander R. Vaccaro, Koen van Besien, Jerrold L. Vitek, Kenneth P. Vives, Timothy W. Vogel, Michael A. Vogelbaum, Dennis G. Vollmer, Gretchen K. Von Allmen, Kajetan L. von Eckardstein, P. Ashley Wackym, Mark Wainwright, Ben Waldau, Marion L. Walker, M. Christopher Wallace, Brian Walsh, Huan Wang, Michael Y. Wang, Vincent Y. Wang, Ronald E. Warnick, Sharon Webb, Ralf Weigel, Robert J. Weil, Jon D. Weingart, Bryce Weir, Martin Weiss, Nirit Weiss, William C. Welch, John C. Wellons, Hung Tzu Wen, Christian Wess, G. Alexander West, Nicholas M. Wetjen, Robert G. Whitmore, Louis A. Whitworth, Thomas Wichmann, Joseph L. Wiemels, Eelco F.M. Wijdicks, Adam C. Wilberger, Jack Wilberger, David M. Wildrick, Jason Wilson, Christopher J. Winfree, H. Richard Winn, Christopher Wolfla, Eric T. Wong, Peter J. Wormald, Margaret Wrensch, Neill M. Wright, Zachary Wright, David Yam, Shinya Yamada, Yoshiya Yamada, Isaac Yang, Victor X.D. Yang, Tom Yao, Chun-Po Yen, H. Kwang Yeoh, Yasuhiro Yonekawa, Alice Yoo, David M. Yousem, Eric C. Yuen, Joseph M. Zabramski, Andrew C. Zacest, J. Christopher Zacko, Gabriel Zada, Ross Zafonte, Eric L. Zager, Hasan A. Zaidi, Hekmat Zarzour, Vasilios A. Zerris, Justin A. Zivin, John G. Zovickian, Alexander Y. Zubkov, and Marike Zwienenberg-Lee

Published
2011
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8. The influence of fibronectin and laminin during Schwann cell migration and peripheral nerve regeneration through silicon chambers

Author

Marc E. Eichler, Keith M. Rich, S. B. Bailey, and Aida Villadiego

Subjects
Silicon, Histology, Schwann cell, Immunoenzyme Techniques, Rats, Sprague-Dawley, Cell Movement, Laminin, medicine, Animals, Peripheral Nerves, biology, General Neuroscience, Regeneration (biology), Schwann cell migration, Cell Biology, Anatomy, Fibronectins, Nerve Regeneration, Rats, Cell biology, Fibronectin, medicine.anatomical_structure, Nerve growth factor, nervous system, Peripheral nervous system, biology.protein, Female, Schwann Cells, Sciatic nerve
Abstract

The ability of extracellular proteins to influence the regenerative process was examined in Sprague-Dawley rats. Silicon chambers, filled with sterile saline solutions of cytochrome-c, fibronectin, laminin, a combination of fibronectin and laminin, or nerve growth factor were surgically implanted between the severed ends of sciatic nerves to form gaps of 18 mm. Four months later, the various groups were examined to determine the success of regeneration. The incidence of cable formation that bridged the gap was similar in all groups. The group of animals that had implants containing the combination of fibronectin/laminin had increased numbers of myelinated axons in the regenerated segment within the chamber and in the distal sciatic tributary nerves. Horseradish peroxidase labelling demonstrated that increased numbers of sensory and motor neurons in the fibronectin/laminin group had regenerated axons across the gap into the distal tributaries of the sciatic nerve. The effect of the various agents on non-neuronal cells was measured by immunohistochemical staining with S-100 antibodies to determine the effects on Schwann cell migration. Silicon chambers, filled with sterile saline solutions of fibronectin, laminin, fibronectin/laminin, nerve growth factor, or cytochrome-c, were surgically implanted to form 5 mm gaps between severed sciatic nerve ends. Ten days later, Schwann cell migration into the bridging cables was examined in each group. Analysis revealed a greater influx of Schwann cells migrating into the regenerating segments in the fibronectin, the laminin, and the combination fibronectin/laminin groups compared to the control group (cytochrome-c).

Published
1993
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9. A comparison of long-term outcomes of translaminar facet screw fixation and pedicle screw fixation: a prospective study

Author

Jayshree Tuli, Marc E. Eichler, Sagun Tuli, and Eric J. Woodard

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, Nonunion, Bone Screws, Screw fixation, Fixation (surgical), medicine, Long term outcomes, Humans, Prospective Studies, Pedicle screw fixation, Prospective cohort study, Proportional Hazards Models, business.industry, Lumbosacral Region, General Medicine, Middle Aged, medicine.disease, Surgery, Spinal Fusion, Treatment Outcome, Lumbar spine, Female, Spinal Diseases, business, Lumbosacral joint
Abstract

Object In this paper, the authors compare the long-term outcomes of translaminar facet screw fixation (TFSF) and pedicle screw fixation (PSF) in the treatment of degenerative lumbosacral disease. Methods This prospective analytical study was performed to compare the long-term outcomes of TFSF and PSF for degenerative lumbosacral disease. Outcomes were defined as the need for reoperation for the development of a nonunion, end-fusion degeneration, or for explantation of hardware. Results A total of 77 patients were analyzed. Thirty-seven patients underwent PSF and 40 received TFSF. Twenty-three of the 77 patients required a reoperation: 13 (32.5%) of the 40 patients in the TFSF group and 10 (27%) of the 37 the patients in the PSF group. The overall mean time to reoperation (regardless of outcome) was 4.05 years. For patients in the TFSF group the mean time to reoperation was 2.94 years, whereas it was 4.35 years in the PSF group (p = 0.34). Nonunion was noted in seven of the 40 patients in the TFSF group and one of 37 in the PSF group. The mean time to surgery for nonunion for patients in the TFSF group was 3.46 years and for those in the PSF group it was 6.27 years (p = 0.04). Surgery for end-fusion degeneration was performed in two patients in the TFSF group and five in the PSF group (p = 0.43). Explantation of hardware was performed in two patients with TFSF and four patients with PSF. Multivariable analysis revealed a statistically significant difference in the time to surgery for nonunion between PSF and TFSF (p = 0.048), with a hazard ratio of 0.097 (95% confidence interval 0.01–0.98). Conclusions Findings from the current prospective study suggest that there is an increased risk of requirement for a reoperation for nonunion among TFSF cases compared with PSF cases.

Published
2007

10. Respiratory Abnormalities Resulting from Midcervical Spinal Cord Injury and their Reversal by Serotonin 1A Agonists in Conscious Rats

Author

Eric J. Woodard, Renna C. Onario, Allyson M. King, Sunil Sabharwal, Walter R. Frontera, Marc E. Eichler, Federico C. Desilets, Kimberly M. Newton, Howard Choi, Yang D. Teng, and Wei-Lee Liao

Subjects
Agonist, Time Factors, medicine.drug_class, Development/Plasticity/Repair, Functional Laterality, Buspirone, Lesion, Rats, Sprague-Dawley, Forelimb, Medicine, Animals, Drug Interactions, Respiratory system, Wakefulness, Spinal cord injury, Spinal Cord Injuries, 8-Hydroxy-2-(di-n-propylamino)tetralin, Analysis of Variance, Behavior, Animal, Dose-Response Relationship, Drug, business.industry, General Neuroscience, Antagonist, Recovery of Function, medicine.disease, Respiration Disorders, Hindlimb, Rats, Serotonin Receptor Agonists, Plethysmography, Anesthesia, Cervical Vertebrae, Female, Serotonin, medicine.symptom, business, Respiratory minute volume, medicine.drug
Abstract

Respiratory dysfunction after cervical spinal cord injury (SCI) has not been examined experimentally using conscious animals, although clinical SCI most frequently occurs in midcervical segments. Here, we report a C5 hemicontusion SCI model in rats with abnormalities that emulate human post-SCI pathophysiology, including spontaneous recovery processes. Post-C5 SCI rats demonstrated deficits in minute ventilation (Ve) responses to a 7% CO2challenge that correlated significantly with lesion severities (no injury or 12.5, 25, or 50 mm × 10 g weight drop; New York University impactor;p< 0.001) and ipsilateral motor neuron loss (p= 0.016). Importantly, C5 SCI resulted in at least 4 weeks of respiratory abnormalities that ultimately recovered afterward. Because serotonin is involved in respiration-related neuroplasticity, we investigated the impact of activating 5-HT1Areceptors on post-C5 SCI respiratory dysfunction. Treatment with the 5-HT1Aagonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH DPAT) (250 μg/kg, i.p.) restored hypercapnic Ve at 2 and 4 weeks after injury (i.e., ∼39.2% increase vs post-SCI baseline;p≤ 0.033). Improvements in hypercapnic Ve response after single administration of 8-OH DPAT were dose dependent and lasted for ∼4 h(p≤ 0.038 andp≤ 0.024, respectively). Treatment with another 5-HT1Areceptor agonist, buspirone (1.5 mg/kg, i.p.), replicated the results, whereas pretreatment with a 5-HT1A-specific antagonist, 4-iodo-N-[2-[4(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (3 mg/kg, i.p.) given 20 min before 8-OH DPAT negated the effect of 8-OH DPAT. These results imply a potential clinical use of 5-HT1Aagonists for post-SCI respiratory disorders.

Published
2005

11. Contributors

Author

Mark F. Abel, Kuniyoshi Abumi, Mark S. Adams, Cary D. Alberstone, Joseph T. Alexander, John A. Anson, Ronald I. Apfelbaum, Paul M. Arnold, L. Brett Babat, Julian E. Bailes, Jamie Baisden, Nevan G. Baldwin, Perry A. Ball, Giancarlo Barolat, H. Hunt Batjer, Thomas W. Bauer, James R. Bean, Brion J. Beerle, Gordon R. Bell, Gregory J. Bennett, Edward C. Benzel, Darren Bergey, Marc L. Bertrand, Mark H. Bilsky, Barry D. Birch, Robert S. Biscup, Kevin Blaylock, Oheneba Boachie-Adjei, Maxwell Boakye, Scott D. Boden, Henry Bohlman, Michael Bolesta, Mary B. Bondy, Christopher M. Boxell, Keith H. Bridwell, Darrell S. Brodke, James Butler, David W. Cahill, Robert C. Cantu, Allen L. Carl, John A. Carrino, John R. Caruso, Andrew G. Chenelle, Joseph S. Cheng, Yong-Jun Cho, Tanvir F. Choudhri, Frank Conguista, Edward S. Connolly, Paul R. Cooper, Jean-Valéry C.E. Coumans, Albert E. Cram, H. Alan Crockard, Richard Crownover, Bryan W. Cunningham, William T. Curry, Joseph F. Cusick, Scott D. Daffner, Mark D. D'Alise, Vinay Deshmukh, Denis DiAngelo, Curtis A. Dickman, Thomas B. Ducker, Scott T. Dull, Stewart B. Dunsker, Michael J. Ebersold, Jason Eckhardt, Bruce L. Ehni, Matthew Eichenbaum, Kurt M. Eichholz, Marc E. Eichler, Samer K. Elbabaa, Sanford E. Emery, Nancy E. Epstein, Jennifer Erdos, Thomas J. Errico, Tom Faciszewski, Michael G. Fehlings, Lisa A. Ferrara, Richard G. Fessler, Kevin T. Foley, Robert M. Galler, John W. German, Alexander J. Ghanayem, Zoher Ghogawala, Vijay K. Goel, Jan Goffin, Ziya L. Gokaslan, Sohrab Gollogly, Jorge Gonzalez-Martinez, James E. Greensmith, Jeffrey D. Gross, Regis W. Haid, Andrea L. Halliday MD, Allan J. Hamilton, Fadi Hanbali, Jürgen Harms, James S. Harrop, Blaine I. Hart, Robert A. Hart, Robert F. Heary, Fraser C. Henderson, Patrick W. Hitchon, James P. Hollowell, Paul J. Holman, John K. Houten, Robert E. Isaacs, Manabu Ito, John A. Jane, J. Patrick Johnson, Christopher Kager, Iain H. Kalfas, George J. Kaptain, Saad Khairi, Daniel H. Kim, David H. Kim, Thomas A. Kopitnik, Robert J. Kowalski, Ajit A. Krishnaney, John A. Lancon, Giuseppe Lanzino, Sanford J. Larson, Jorge Lastra-Power, Nathan H. Lebwohl, Isador H. Lieberman, Donlin M. Long, Mark G. Luciano, Charles A. Luevano, Parley M. Madsen III, Dennis J. Maiman, Jacek M. Malik, David G. Malone, Joseph C. Maroon, Eric M. Massicotte, Shunji Matsunaga, Daniel J. Mazanec, Paul C. McAfee, Bruce M. McCormack, Paul C. McCormick, William E. McCormick, Robert A. McGuire, Robert F. McLain, Nagy Mekhail, D. Mark Melton, Carole A. Miller, Jared H. Miller, Sung Min, William Mitchell, Junichi Mizuno, Michael T. Modic, Howard W. Morgan, Robert J. Morlock, Michael A. Morone, Wade M. Mueller, Praveen V. Mummaneni, John S. Myseros, Sait Naderi, Dileep Nair, Hiroshi Nakagawa, Jaime H. Nieto, Russ P. Nockels, Bruce E. Northrup, Chima Ohaegbulam, Tunc Oktenoglu, Bernardo Jose Ordonez, Jeffrey H. Owen, A. Fahir Özer, Stephen M. Papadopoulos, Christopher G. Paramore, Robert S. Pashman, Warwick J. Peacock, Stanley Pelofsky, Noel I. Perin, Christopher J. Pham, Rick J. Placide, Branko Prpa, Gregory J. Przybylski, Ashraf A. Ragab, Y. Raja Rampersaud, Peter A. Rasmussen, Richard B. Raynor, Gary L. Rea, Glenn R. Rechtine, John Regan, Setti S. Rengachary, Daniel K. Resnick, Laurence D. Rhines, Albert J. Rhoton, Donna J. Rodriguez, Gerald E. Rodts, Michael J. Rosner, Alexander Sah, Jared P. Salinsky, Paul Santiago, Mehdi Sarkarati, Richard L. Saunders, Paul D. Sawin, Edward H. Scheid, Meic H. Schmidt, Michael Schneier, Dilip K. Sengupta, Christopher I. Shaffrey, Mark E. Shaffrey, Alok D. Sharan, Ashwini D. Sharan, Christopher B. Shields, Frederick A. Simeone, Kern Singh, Ran Vijai P. Singh, Donald A. Smith, Maurice M. Smith, Volker K.H. Sonntag, Ivan J. Sosa, Micheal J. Speck, Robert F. Spetzler, Sudhakar T. Sridharan, Loretta A. Staudt, Michael P. Steinmetz, Charles B. Stillerman, Kota Suda, Sonia Suys, George W. Sypert, Charles H. Tator, Nicholas Theodore, Ajith J. Thomas, Nicholas W.M. Thomas, Robert E. Tibbs, Daisuke Togawa, Frank J. Tomecek, Richard M. Toselli, Vincent C. Traynelis, Gregory R. Trost, Eeric Truumees, Gary W. Tye, Abm Salah Uddin, Alexander R. Vaccaro, Ceslovas Vaicys, Alex Valadka, Arnold B. Vardiman, Anthony A. Virella, Elizabeth Vitarbo, Todd W. Vitaz, Dennis G. Vollmer, Jean-Marc Voyadzis, John D. Ward, Joseph Watson, John K. Webb, Philip R. Weinstein, Martin W. Weiser, William C. Welch, Simcha J. Weller, L. Erik Westerlund, Jonathan A. White, Melvin D. Whitfield, Gregory C. Wiggins, Jack E. Wilberger, William S. Wilke, Diana Barrett Wiseman, W. Putnam Wolcott, Eric J. Woodard, Philip Yazback, Narayan Yoganandan, Kenneth S. Yonemura, Kazuo Yonenobu, Hansen A. Yuan, Seth M. Zeidman, Barry M. Zide, and Mehmet Zileli

Published
2005
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12. New Directions in Spinal Surgery

Author

Marc E. Eichler and Ian F. Dunn

Subjects
medicine.medical_specialty, Surgical approach, Minimal access, business.industry, medicine.medical_treatment, Vertebral compression fracture, Laminectomy, medicine.disease, Spinal surgery, Surgery, Percutaneous vertebroplasty, Spine surgery, Discectomy, medicine, business
Abstract

Evolving technological sophistication has resulted in ongoing modifications of traditional surgical approaches to correct disorders of the spinal axis. Advances in instrumentation and pre- and intraoperative imaging have fueled a move toward minimally invasive, minimal access spine surgery (1), by which the same surgical goals of conventional open techniques are met through a smaller access corridor. An early and now well-accepted example is the surgical approach to a herniated paracentral lumbar disc, originally performed via complete laminectomy and now performed by microsurgical discectomy thorough a 15–25-mm incision and hemilaminectomy.

Published
2005
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14. Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Author

Howard Choi, Marc E. Eichler, Shoumin Lan, Federico C. Desilets, Shan Zhu, Eric J. Woodard, Renna C. Onario, Robert M. Friedlander, Evan Y. Snyder, and Yang D. Teng

Subjects
Minocycline, Pharmacology, Microgliosis, Neuroprotection, Rats, Sprague-Dawley, medicine, Animals, Spinal cord injury, Spinal Cord Injuries, Multidisciplinary, Glial fibrillary acidic protein, biology, Chemistry, Cytochrome c, Body Weight, Cytochromes c, Biological Sciences, medicine.disease, Spinal cord, Astrogliosis, Mitochondria, Rats, Disease Models, Animal, Kinetics, Oligodendroglia, medicine.anatomical_structure, Spinal Cord, Astrocytes, biology.protein, Female, medicine.drug
Abstract

We investigated whether permeability transition-mediated release of mitochondrial cytochrome c is a potential therapeutic target for treating acute spinal cord injury (SCI). Based on previous reports, minocycline, a second-generation tetracycline, exerts neuroprotection partially by inhibiting mitochondrial cytochrome c release and reactive microgliosis. We first evaluated cytochrome c release at the injury epicenter after a T10 contusive SCI in rats. Cytochrome c release peaked at ≈4-8 h postinjury. A dose-response study generated a safe pharmacological regimen that enabled i.p. minocycline to significantly lower cytosolic cytochrome c at the epicenter 4 h after SCI. In the long-term study, i.p. minocycline (90 mg/kg administered 1 h after SCI followed by 45 mg/kg administered every 12 h for 5 days) markedly enhanced long-term hind limb locomotion relative to that of controls. Coordinated motor function and hind limb reflex recoveries also were improved significantly. Histopathology suggested that minocycline treatment alleviated later-phase tissue loss, with significant sparing of white matter and ventral horn motoneurons at levels adjacent to the epicenter. Furthermore, glial fibrillary acidic protein and 2′,3′ cyclic nucleotide 3′ phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. Therefore, release of mitochondrial cytochrome c is an important secondary injury mechanism in SCI. Drugs with multifaceted effects in antagonizing this process and microgliosis may protect a proportion of spinal cord tissue that is clinically significant for functional recovery. Minocycline, with its proven clinical safety, capability to cross the blood-brain barrier, and demonstrated efficacy during a clinically relevant therapeutic window, may become an effective therapy for acute SCI.

Published
2004

15. Contributors

Author

Robert J. Adams, James W. Albers, Lloyd M. Alderson, Michael P. Alexander, Anthony A. Amato, Sepideh Amin-Hanjani, Richard M. Armstrong, Gerald M. Aronoff, Ajay K. Arora, Tetsuo Ashizawa, Viken L. Babikian, Joachim M. Baehring, Zahid H. Bajwa, Robert W. Baloh, Patrick D. Barnes, Richard J. Barohn, Steven M. Baskin, Isabelita R. Bella, Richard J. Benjamin, Alan R. Berger, Susan Biener Bergman, Marcelo E. Bigal, José Biller, Peter McLaren Black, Charles F. Bolton, David Borsook, Lawrence M. Brass, Jon Brillman, Edward B. Bromfield, Robert H. Brown, John C.M. Brust, Louis R. Caplan, David A. Chad, Michael E. Charness, Marc I. Chimowitz, Catherine Cho, Cathy Chuang, Winthrop H. Churchill, Alan R. Cohen, Douglas G. Cole, John P. Conomy, Clifford C. Dacso, Kirk R. Daffner, Josep O. Dalmau, Basil T. Darras, Patricia H. Davis, David M. Dawson, Lisa M. DeAngelis, Umberto De Girolami, L. Dana DeWitt, Luis D'Olhaberriague, Frank W. Drislane, Edward J. Dropcho, Bruce Ehrenberg, Marc E. Eichler, Conrado J. Estol, Bradley K. Evans, Gilbert J. Fanciullo, Robert G. Feldman, Steven K. Feske, Scott M. Fishman, Barry S. Fogel, Roy L. Freeman, Joseph H. Friedman, Matthew P. Frosch, Melissa Frumin, Anthony J. Furlan, George A. Gates, David S. Geckle, Thomas P. Giordano, Mel B. Glenn, Martin A. Goldstein, Christopher M. Gomez, Clifton L. Gooch, Francesc R. Graus, Harry S. Greenberg, Stephen B. Greenberg, Melvin Greer, Robert C. Griggs, Sheldon G. Gross, Stuart A. Grossman, Michael L. Gruber, Ludwig Gutmann, Walter A. Hall, Mark Hallett, Julie E. Hammack, Yadollah Harati, Richard L. Harris, Christopher H. Hawkes, Michael T. Hayes, David N. Herrmann, Fred H. Hochberg, Dave Hollander, Gregory L. Holmes, Liangge Hsu, Daniel M. Jacobson, Robert N. Jamison, Joseph Jankovic, Tom J. Jeerakathil, Donald R. Johns, H. Royden Jones, Henry J. Kaminski, Percy N. Karanjia, Carlos S. Kase, Bashar Katirji, Jonathan S. Katz, Nathaniel P. Katz, John J. Kelly, Drew S. Kern, Shahram Khoshbin, Howard S. Kirshner, Edwin H. Kolodny, Bruce R. Korf, Walter J. Koroshetz, Lauren B. Krupp, David B. Kudrow, Rajeev Kumar, Robert S. Kunkel, Roger Kurlan, David Lacomis, Eugene C. Lai, Robert Laureno, Susan LaViolette, J. Douglas Lee, Edward J. Levine, Robert Aaron Levine, Steven R. Levine, Peter LeWitt, Mark H. Libenson, Richard B. Lipton, Grant T. Liu, Elizabeth W. Loder, Jay S. Loeffler, Eric L. Logigian, Betsy B. Love, Steven Lovitt, Jeffrey D. Macklis, Ami K. Mankodi, Frederick J. Marshall, Randall S. Marshall, Jean K. Matheson, Kathleen McEvoy, Robert R. McKendall, Daniel Miller, Edison Miyawaki, J.P. Mohr, Fiona Molloy, Patricia M. Moore, Michael Mufson, Sharon P. Nations, Craig Patrick Nolan, Patrick E. Nolan, Thorkild V. Norregaard, Kathryn N. North, Cormac A. O'Donovan, Chima O. Ohaegbulam, Richard K. Olney, Russell C. Packard, John K. Park, Roy A. Patchell, John R. Peteet, Ronald C. Petersen, Kendra Peterson, Jackson B. Pickett, William F. Pirl, Scott R. Plotkin, Scott L. Pomeroy, Frisso Potts, Daniel Press, David C. Preston, Bruce H. Price, Amy Pruitt, Michael T. Pulley, Naren Ramakrishna, Alan M. Rapoport, Paula Ravin, Elizabeth M. Raynor, Lawrence D. Recht, Kurt Reed, Dorene M. Rentz, Gary S. Richardson, Jeffrey M. Robbins, Diana L. Rodriguez, Loren Rolak, Michael Ronthal, Patrick A. Roth, Jeffrey D. Rothstein, Robert L. Ruff, James A. Russell, Thomas D. Sabin, Ahmed H. Sadek, Eileen Salmanson, Nalini Samuel, Martin A. Samuels, Steven C. Schachter, David Schiff, Donald Schomer, H. Christian Schumacher, R. Michael Scott, Elizabeth A. Sekul, Barbara E. Shapiro, Nutan Sharma, Jeremy M. Shefner, Fred D. Sheftell, Dennis C. Shrieve, Joao O. Siffert, Cathy A. Sila, Carlos Singer, Marca L. Sipski, Linda A. Specht, Egilius L.H. Spierings, Steven Spindel, Barney J. Stern, Lael A. Stone, Guillermo A. Suarez, Lewis R. Sudarsky, Kathryn Swoboda, William T. Talman, Nancy J. Tarbell, Daniel Tarsy, Philip A. Teal, Siew Koon Teoh, Daryl W. Thompson, William R. Tyor, Nagagopal Venna, David M. Vernick, Aljoeson Walker, Carol A. Warfield, Cheryl Waters, Lawrence R. Wechsler, Randall E. Weeks, David H. Weinberg, Sandra Weintraub, Dennis Y. Wen, Patrick Y.C. Wen, Janice F. Wiesman, Asa J. Wilbourn, Temple W. Williams, Barth L. Wilsey, Philip A. Wolf, G. Bryan Young, and Amir Zamani

Published
2003
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16. The ability of diphenylpiperazines to prevent neuronal death in dorsal root ganglion neurons in vitro after nerve growth factor deprivation and in vivo after axotomy

Author

Janet M. Dubinsky, Jianxin Tong, Marc E. Eichler, and Keith M. Rich

Subjects
Fura-2, Cell Survival, medicine.medical_treatment, Pharmacology, Biology, Biochemistry, Neuroprotection, Calcium in biology, Piperazines, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Dorsal root ganglion, Ganglia, Spinal, medicine, Animals, Nerve Growth Factors, Cells, Cultured, Neurons, Dose-Response Relationship, Drug, Calcium channel, Intracellular Membranes, Calcium Channel Blockers, Denervation, Sensory neuron, Axons, Rats, medicine.anatomical_structure, Nerve growth factor, nervous system, chemistry, Potassium, Calcium, Axotomy, Extracellular Space, Neuroscience
Abstract

The mechanism of neuroprotection by the calcium channel antagonist flunarizine against neuronal death is unknown. We investigated the ability of other calcium channel antagonists (cinnarizine, nimodipine, nicardipine, diltiazem, and verapamil), calmodulin antagonists, and calpain inhibitors to prevent neuronal death in rat dorsal root ganglion neurons in vitro after nerve growth factor (NGF) deprivation and the ability of cinnarizine and diltiazem to protect in vivo after axotomy. In vitro, only neurons treated with cinnarizine or flunarizine were protected from death after withdrawal. In vivo, cinnarizine, but not diltiazem, protected dorsal root ganglion neurons in rats after unilateral sciatic nerve crush. Intracellular calcium concentration ([Ca2+]i) was evaluated with fura 2 after NGF deprivation in vitro. Neurons "committed to die" 24 h after NGF deprivation displayed a decline in [Ca2+]i before visible morphological deterioration consistent with cell death. The influx of extracellular calcium was not necessary to produce neuronal death. Neurons deprived of NGF gradually lost the ability to respond to elevated external potassium with an increase in [Ca2+]i during the first 24 h after trophic factor deprivation. After 24 h, neurons deprived of NGF could not be rescued by readministration of NGF. Neurons protected from cell death with diphenylpiperazines maintained their response to high external potassium, suggesting continued membrane integrity. We speculate that diphenylpiperazines may protect sensory neurons via an unknown mechanism that stabilizes cell membranes.

Published
1994

17. Relationship of intracellular calcium to dependence on nerve growth factor in dorsal root ganglion neurons in cell culture

Author

Janet M. Dubinsky, Keith M. Rich, and Marc E. Eichler

Subjects
Cell Survival, chemistry.chemical_element, Biology, Calcium, Biochemistry, Calcium in biology, Cellular and Molecular Neuroscience, Embryonic and Fetal Development, Dorsal root ganglion, Ganglia, Spinal, medicine, Animals, Nerve Growth Factors, Cells, Cultured, Cellular Senescence, Neurons, Intracellular Membranes, Sensory neuron, Cell biology, medicine.anatomical_structure, Nerve growth factor, nervous system, chemistry, Cell culture, Potassium, Neuroscience, Cell aging, Intracellular
Abstract

During development, neural crest-derived sensory neurons require nerve growth factor (NGF) for survival, but lose this dependency postnatally. Similarly, dissociated embryonic sensory neurons lose their NGF dependence during the first 3 weeks in cell culture. It has been hypothesized that, in sympathetic neurons, intracellular levels of calcium are related to trophic factor dependence. In vitro during the period in which embryonic-day-15 sensory neurons become independent of NGF, intracellular calcium concentrations progressively increased in parallel to the decline in NGF dependence. This elevation of intracellular calcium was directly related to the absolute age of the neurons, not to the length of time in culture. Without NGF, immature sensory, i.e., dependent, neurons survived in the presence of high extracellular potassium, a condition that produces elevated intracellular calcium. In another paradigm, measurements of intracellular calcium were determined in NGF-dependent neurons "committed to die" after NGF withdrawal. These measurements were determined prior to the time that extensive morphological changes, consistent with cell death, were noted by phase-contrast microscopy. No elevation in intracellular calcium was found in these dying neurons, but rather, a small decrease was observed prior to the disintegration of the neurons. These findings support the hypothesis that trophic factor dependence of neurons may be inversely related to levels of intracellular calcium.

Published
1992

18. Flunarizine protects sensory and sympathetic neurones from death after NGF withdrawal and axotomy: a possible role of intracellular calcium in determining trophic factor dependence

Author

Keith M. Rich, Marc E. Eichler, Janet M. Dubinsky, and J.P. Hollowell

Subjects
Physiology, Chemistry, General Neuroscience, medicine.medical_treatment, medicine, Sensory system, Neurology (clinical), Axotomy, Flunarizine, Neuroscience, Calcium in biology, medicine.drug, Trophic level
Published
1991
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19. Death of sensory ganglion neurons after acute withdrawal of nerve growth factor in dissociated cell cultures

Author

Marc E. Eichler and Keith M. Rich

Subjects
medicine.medical_specialty, Time Factors, Cell Survival, Sensory system, Cell Count, Nerve Tissue Proteins, Methionine, Dorsal root ganglion, Internal medicine, Ganglia, Spinal, medicine, Animals, Nerve Growth Factors, Neurons, Afferent, Molecular Biology, Cells, Cultured, biology, business.industry, General Neuroscience, Rats, Inbred Strains, Rats, medicine.anatomical_structure, Nerve growth factor, Endocrinology, nervous system, Sensory Ganglion, Cell culture, Peripheral nervous system, biology.protein, Neurology (clinical), Neuron, business, Developmental Biology, Neurotrophin
Abstract

The time course of dependence on nerve growth factor (NGF) for survival in sensory neurons in vitro was examined with microscopic and biochemical methods. Primary dorsal root ganglion (DRG) cultures from embryonic-day-15 (E-15) and day-19 (E-19) rats were maintained with standard dissociated cell culture techniques in the absence of most non-neuronal cells. After various times in culture, neurons were acutely deprived of neurotrophic support by changing to NGF-free medium and adding NGF antiserum to eliminate any residual NGF. Neuronal cultures were examined with phase microscopy; and, their metabolic activity was measured with a protein assay at various time points after NGF deprivation. E-15 neurons grown in culture for 5 days were exquisitely sensitive to acute NGF deprivation. By 12 h after NGF deprivation, neuronal morphology was severely disrupted and the majority of neurons appeared dead. E-15 neurons grown in culture for 8 or 11 days showed progressively less dependence on NGF for survival. These older neurons did not die until 24 and 48 h, respectively, following NGF withdrawal. Neurons grown in culture for 20 days did not show any morphologic changes by phase microscopy up to 4 days after NGF deprivation. Protein incorporation progressively decreased between 12 and 48 h after NGF withdrawal in E-15 neurons grown in culture for 5, 8, or 11 days. The younger neurons were more sensitive to NGF withdrawal at earlier time points. E-15 neurons grown in culture for 20 days showed only a 20% decrease in protein metabolism at 24, 48, and 108 h after NGF withdrawal and did not require NGF for survival. A second group of neurons from E-19 rat pups was cultured to determine whether the loss of NGF dependence for survival was related to the time in culture or to the absolute age of the neurons. The E-19 neurons were deprived of NGF in the same fashion as the E-15 neurons cultured for 6 days (absolute age, 21 days) underwent death by 12 h after NGF withdrawal. In contrast, E-19 neurons cultured for 6 days (absolute age, 25 days) were alive 24 h after NGF deprivation. Thus, it appears that the absolute age of the neuron rather than the length of time in culture determines its sensitivity to NGF deprivation, Embryonic sensory neurons demonstrate dramatic changes in NGF dependence in vitro. This change in sensory neuronal dependence on trophic support is related to the absolute age of the neurons rather than the length of time in culture. Trophic requirements change during development as a result of unknown intrinsic neuronal mechanisms.

Published
1989

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