====== Jerry Silver, Ph.D. ====== #template(faculty_profile.php|... * FName: Jerry * LName: Silver * Degree: Ph.D. * Picture: silver-1.jpg * Position: Professor * Department: Department of Neurosciences * Organization: Case Western Reserve University * Address_1: School of Medicine E653 * Address_2: 10900 Euclid Ave * Address_3: Cleveland OH, 44106-4975 * Phone: (216) 368-2150 * Fax: (216) 368-4650 * Email: jxs10@case.edu * PubMed_Search: Silver J + Case Western )# ===== RESEARCH INTERESTS ===== My current research focuses on the role of extrinsic factors in guiding developing and regenerating axons along their proper pathways within the brain and spinal cord of mammals. We are particularly interested in studying the cellular and molecular interactions that occur between axonal growth cones and the various types of glial cells that lie along the presumptive routes and at the boundaries of several different fiber systems in the CNS. We now know that a variety of cell surface and extracellular matrix molecules that stimulate or inhibit axon growth are made by astroglia during a critical period in development. However, as astroglia mature they change dramatically and alter their interactions with growing axons especially following lesions. Thus, following injury in the adult CNS, so-called reactive astroglia actively block rather than promote sustained axonal elongation. We have concentrated our efforts over the past several years learning whether the boundary molecules that astroglia make during normal development are re-expressed after injury. One of the most interesting families of extracellular matrix molecules, the proteoglycans, were first discovered by my lab to be major players in creating developmental as well as regenerative boundaries. It is our hope that the understanding of normal and abnormal mechanisms of axon guidance will suggest regeneration strategies for altering or overcoming inhibitory molecules that are made in excess. To this end we have developed a microtransplantation technique which enables us to gently inject fully adult neurons into normal or lesioned white matter tracts of the adult CNS, without causing the formation of additional reactive astroglial associated inhibitory molecules via the transplantation itself. Remarkably, the adult nerve cells can regenerate their axons with high efficiency and at high rates of speed challenging long held beliefs that this is impossible. Importantly, the rapidly regenerating axons halt their growth when they reach the glial scar, providing the strongest evidence to date of the major importance of the proteoglycan laden lesion environment in regeneration failure. We have also developed //in vitro// assays using gradients of proteoglycans that, like the //in vivo// glial scar, create dystrophic endings on regenerating adult axons. We can now, for the first time, begin to dissect the molecular and cellular machinery of this unusual axonal ending. Many unanswered and provocative questions remain about the potential for neuronal circuit restoration in the regenerated adult CNS and our lab is now in a strong position to begin answering many of them. Indeed, we have recently been able to promote robust functional regeneration into the adult rodent spinal cord of severed sensory roots using a combinatorial strategy that maximally stimulates an intrinsic growth response in the sensory neurons while simultaneously removing inhibitory proteoglycans from the cord with a bacterial enzyme (ie., chondroitinase) that removes the inhibitory sugar chains from proteoglycans. An even more exciting development is our recent demonstration that combining an autologous peripheral nervous system “bridge” with inhibitory matrix modification via chondroitinase leads to robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord. This result, in particular, may have far ranging beneficial clinical consequences. Other labs around the world are now showing that the use of chondroitinase combined with various cell bridging techniques and an enhancement of the neurons intrinsic growth response can restore function in other regeneration models and in other species of mammals. It is highly conceivable that such therapeutic strategies may be useful in restoring both sensory and motor function in paralyzed humans. ===== SELECTED PUBLICATIONS ===== #template?key=Silver(dokudata.php|... ---- * ID: 15607938 * Author: Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J. * Volume: 28 * Issue: 1 * Year: 2005 * Date: 2005 Jan * Journal: Mol Cell Neurosci * Pages: 18-29 * Title: The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. * Selected: true ---- * ID: 15496664 * Author: Tom VJ, Doller CM, Malouf AT, Silver J. * Volume: 24 * Issue: 42 * Year: 2004 * Date: 2004 Oct 20 * Journal: J Neurosci * Pages: 9282-9290 * Title: Astrocyte-associated fibronectin is critical for axonal regeneration in adult white matter. * Selected: true ---- * ID: 15269264 * Author: Tom VJ, Steinmetz MP, Miller JH, Doller CM, Silver J. * Volume: 24 * Issue: 29 * Year: 2004 * Date: 2004 Jul 21 * Journal: J Neurosci * Pages: 6531-6539 * Title: Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. * Selected: true ---- * ID: 14960611 * Author: Grimpe B, Silver J. * Volume: 24 * Issue: 6 * Year: 2004 * Date: 2004 Feb 11 * Journal: J Neurosci * Pages: 1393-1397 * Title: A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. * Selected: true ---- * ID: 14735117 * Author: Silver J, Miller JH. * Volume: 5 * Issue: 2 * Year: 2004 * Date: 2004 Feb * Journal: Nat Rev Neurosci * Pages: 146-156 * Title: Regeneration beyond the glial scar. * Selected: true ---- * ID: 14724244 * Author: Butler CD, Schnetz SA, Yu EY, Davis JB, Temple K, Silver J, Malouf AT. * Volume: 24 * Issue: 2 * Year: 2004 * Date: 2004 Jan 14 * Journal: J Neurosci * Pages: 462-473 * Title: Keratan sulfate proteoglycan phosphacan regulates mossy fiber outgrowth and regeneration. * Selected: true ---- * ID: 12546819 * Author: Hendricks TJ, Fyodorov DV, Wegman LJ, Lelutiu NB, Pehek EA, Yamamoto B, Silver J, Weeber EJ, Sweatt JD, Deneris ES. * Volume: 37 * Issue: 2 * Year: 2003 * Date: 2003 Jan 23 * Journal: Neuron * Pages: 233-247 * Title: Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior. * Selected: true ---- * ID: 12440376 * Author: Grimpe B, Silver J. * Volume: 137 * Issue: * Year: 2002 * Date: 2002 * Journal: Prog Brain Res * Pages: 333-349 * Title: The extracellular matrix in axon regeneration. * Selected: true ---- * ID: 11943817 * Author: Grimpe B, Dong S, Doller C, Temple K, Malouf AT, Silver J. * Volume: 22 * Issue: 8 * Year: 2002 * Date: 2002 Apr 15 * Journal: J Neurosci * Pages: 3144-3160 * Title: The critical role of basement membrane-independent laminin gamma 1 chain during axon regeneration in the CNS. * Selected: true ---- * ID: 11716550 * Author: Silver J. * Volume: 172 * Issue: 2 * Year: 2001 * Date: 2001 Dec * Journal: Exp Neurol * Pages: 255-256 * Title: Robust regeneration in the adult optic system. * Selected: true ---- * ID: 10493720 * Author: Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. * Volume: 19 * Issue: 19 * Year: 1999 * Date: 1999 Oct 1 * Journal: J Neurosci * Pages: 8182-8198 * Title: Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. * Selected: true ---- * ID: 10407022 * Author: Davies SJ, Goucher DR, Doller C, Silver J. * Volume: 19 * Issue: 14 * Year: 1999 * Date: 1999 Jul 15 * Journal: J Neurosci * Pages: 5810-5822 * Title: Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. * Selected: true ---- * ID: 10028921 * Author: Xu K, Malouf AT, Messing A, Silver J. * Volume: 25 * Issue: 4 * Year: 1999 * Date: 1999 Feb 15 * Journal: Glia * Pages: 390-403 * Title: Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid. * Selected: true ---- * ID: 9500964 * Author: DeWitt DA, Perry G, Cohen M, Doller C, Silver J. * Volume: 149 * Issue: 2 * Year: 1998 * Date: 1998 Feb * Journal: Exp Neurol * Pages: 329-340 * Title: Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease. * Selected: true ---- * ID: 9417835 * Author: Fitch MT, Silver J. * Volume: 148 * Issue: 2 * Year: 1997 * Date: 1997 Dec * Journal: Exp Neurol * Pages: 587-603 * Title: Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. * Selected: true ---- * ID: 9414159 * Author: Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J. * Volume: 390 * Issue: 6661 * Year: 1997 * Date: 1997 Dec 18-25 * Journal: Nature * Pages: 680-683 * Title: Regeneration of adult axons in white matter tracts of the central nervous system. * Selected: true ---- * ID: 9321701 * Author: Fitch MT, Silver J. * Volume: 290 * Issue: 2 * Year: 1997 * Date: 1997 Nov * Journal: Cell Tissue Res * Pages: 379-384 * Title: Glial cell extracellular matrix: boundaries for axon growth in development and regeneration. * Selected: true ---- * ID: 8912902 * Author: DeWitt DA, Silver J. * Volume: 142 * Issue: 1 * Year: 1996 * Date: 1996 Nov * Journal: Exp Neurol * Pages: 103-110 * Title: Regenerative failure: a potential mechanism for neuritic dystrophy in Alzheimer's disease. * Selected: true ---- * ID: 8842795 * Author: Canning DR, Hoke A, Malemud CJ, Silver J. * Volume: 14 * Issue: 3 * Year: 1996 * Date: 1996 Jun * Journal: Int J Dev Neurosci * Pages: 153-175 * Title: A potent inhibitor of neurite outgrowth that predominates in the extracellular matrix of reactive astrocytes. * Selected: true ---- * ID: 8979800 * Author: Hoke A, Silver J. * Volume: 108 * Issue: * Year: 1996 * Date: 1996 * Journal: Prog Brain Res * Pages: 149-163 * Title: Proteoglycans and other repulsive molecules in glial boundaries during development and regeneration of the nervous system. * Selected: true ---- * ID: 7589332 * Author: McKeon RJ, Hoke A, Silver J. * Volume: 136 * Issue: 1 * Year: 1995 * Date: 1995 Nov * Journal: Exp Neurol * Pages: 32-43 * Title: Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. * Selected: true ---- * ID: 8581314 * Author: Brittis PA, Lemmon V, Rutishauser U, Silver J. * Volume: 6 * Issue: 5 * Year: 1995 * Date: 1995 Oct * Journal: Mol Cell Neurosci * Pages: 433-449 * Title: Unique changes of ganglion cell growth cone behavior following cell adhesion molecule perturbations: a time-lapse study of the living retina. * Selected: true ---- * ID: 8581313 * Author: Brittis PA, Silver J. * Volume: 6 * Issue: 5 * Year: 1995 * Date: 1995 Oct * Journal: Mol Cell Neurosci * Pages: 413-432 * Title: Multiple factors govern intraretinal axon guidance: a time-lapse study. * Selected: true ---- * ID: 7672030 * Author: Brittis PA, Meiri K, Dent E, Silver J. * Volume: 134 * Issue: 1 * Year: 1995 * Date: 1995 Jul * Journal: Exp Neurol * Pages: 1-12 * Title: The earliest patterns of neuronal differentiation and migration in the mammalian central nervous system. * Selected: true ---- * ID: 7535345 * Author: Silver J. * Volume: 242 * Issue: 1 Suppl 1 * Year: 1994 * Date: 1994 Dec * Journal: J Neurol * Pages: S22-S24 * Title: Inhibitory molecules in development and regeneration. * Selected: true ---- * ID: 7821397 * Author: Hoke A, Canning DR, Malemud CJ, Silver J. * Volume: 130 * Issue: 1 * Year: 1994 * Date: 1994 Nov * Journal: Exp Neurol * Pages: 56-66 * Title: Regional differences in reactive gliosis induced by substrate-bound beta-amyloid. * Selected: true ---- * ID: 7523632 * Author: Gonzalez ML, Silver J. * Volume: 14 * Issue: 10 * Year: 1994 * Date: 1994 Oct * Journal: J Neurosci * Pages: 6121-6131 * Title: Axon-glia interactions regulate ECM patterning in the postnatal rat olfactory bulb. * Selected: true ---- * ID: 7804839 * Author: DeWitt DA, Richey PL, Praprotnik D, Silver J, Perry G. * Volume: 656 * Issue: 1 * Year: 1994 * Date: 1994 Sep 5 * Journal: Brain Res * Pages: 205-209 * Title: Chondroitin sulfate proteoglycans are a common component of neuronal inclusions and astrocytic reaction in neurodegenerative diseases. * Selected: true ---- * ID: 7807592 * Author: Frisa PS, Goodman MN, Smith GM, Silver J, Jacobberger JW. * Volume: 39 * Issue: 1 * Year: 1994 * Date: 1994 Sep 1 * Journal: J Neurosci Res * Pages: 47-56 * Title: Immortalization of immature and mature mouse astrocytes with SV40 T antigen. * Selected: true ---- * ID: 8052616 * Author: Brittis PA, Silver J. * Volume: 91 * Issue: 16 * Year: 1994 * Date: 1994 Aug 2 * Journal: Proc Natl Acad Sci U S A * Pages: 7539-7542 * Title: Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium. * Selected: true ---- * ID: 8173316 * Author: Herrup K, Silver J. * Volume: 4 * Issue: 1 * Year: 1994 * Date: 1994 Feb * Journal: Curr Opin Neurobiol * Pages: 108-111 * Title: Cortical development and topographic maps: patterns of cell dispersion in developing cerebral cortex. * Selected: true ---- * ID: 7850360 * Author: Hoke A, Silver J. * Volume: 2 * Issue: 3 * Year: 1994 * Date: 1994 * Journal: Perspect Dev Neurobiol * Pages: 269-274 * Title: Heterogeneity among astrocytes in reactive gliosis. * Selected: true ---- * ID: 8287928 * Author: Canning DR, McKeon RJ, DeWitt DA, Perry G, Wujek JR, Frederickson RC, Silver J. * Volume: 124 * Issue: 2 * Year: 1993 * Date: 1993 Dec * Journal: Exp Neurol * Pages: 289-298 * Title: beta-Amyloid of Alzheimer's disease induces reactive gliosis that inhibits axonal outgrowth. * Selected: true ---- * ID: 8405282 * Author: Gonzalez Mde L, Malemud CJ, Silver J. * Volume: 123 * Issue: 1 * Year: 1993 * Date: 1993 Sep * Journal: Exp Neurol * Pages: 91-105 * Title: Role of astroglial extracellular matrix in the formation of rat olfactory bulb glomeruli. * Selected: true ---- * ID: 8374779 * Author: Goodman MN, Silver J, Jacobberger JW. * Volume: 619 * Issue: 1-2 * Year: 1993 * Date: 1993 Aug 13 * Journal: Brain Res * Pages: 199-213 * Title: Establishment and neurite outgrowth properties of neonatal and adult rat olfactory bulb glial cell lines. * Selected: true ---- * ID: 8339766 * Author: DeWitt DA, Silver J, Canning DR, Perry G. * Volume: 121 * Issue: 2 * Year: 1993 * Date: 1993 Jun * Journal: Exp Neurol * Pages: 149-152 * Title: Chondroitin sulfate proteoglycans are associated with the lesions of Alzheimer's disease. * Selected: true ---- * ID: 7680631 * Author: Pindzola RR, Doller C, Silver J. * Volume: 156 * Issue: 1 * Year: 1993 * Date: 1993 Mar * Journal: Dev Biol * Pages: 34-48 * Title: Putative inhibitory extracellular matrix molecules at the dorsal root entry zone of the spinal cord during development and after root and sciatic nerve lesions. * Selected: true ---- * ID: 8440789 * Author: Silver J, Edwards MA, Levitt P. * Volume: 328 * Issue: 3 * Year: 1993 * Date: 1993 Feb 15 * Journal: J Comp Neurol * Pages: 415-436 * Title: Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain. * Selected: true ---- * ID: 8087547 * Author: Silver J. * Volume: 1 * Issue: 4 * Year: 1993 * Date: 1993 * Journal: Perspect Dev Neurobiol * Pages: 227-236 * Title: Glia-neuron interactions at the midline of the developing mammalian brain and spinal cord. * Selected: true ---- * ID: 1738848 * Author: Brittis PA, Canning DR, Silver J. * Volume: 255 * Issue: 5045 * Year: 1992 * Date: 1992 Feb 7 * Journal: Science * Pages: 733-736 * Title: Chondroitin sulfate as a regulator of neuronal patterning in the retina. * Selected: true ---- * ID: 1719160 * Author: McKeon RJ, Schreiber RC, Rudge JS, Silver J. * Volume: 11 * Issue: 11 * Year: 1991 * Date: 1991 Nov * Journal: J Neurosci * Pages: 3398-3411 * Title: Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. * Selected: true ---- * ID: 1915721 * Author: Lefkowitz M, Durand D, Smith G, Silver J. * Volume: 113 * Issue: 3 * Year: 1991 * Date: 1991 Sep * Journal: Exp Neurol * Pages: 306-313 * Title: Electrical properties of axons within probst bundles of acallosal mice and callosi that have reformed upon glial-coated polymer implants. * Selected: true ---- * ID: 2010752 * Author: Watanabe M, Rutishauser U, Silver J. * Volume: 22 * Issue: 1 * Year: 1991 * Date: 1991 Jan * Journal: J Neurobiol * Pages: 85-96 * Title: Formation of the retinal ganglion cell and optic fiber layers. * Selected: true ---- * ID: 2230948 * Author: Rudge JS, Silver J. * Volume: 10 * Issue: 11 * Year: 1990 * Date: 1990 Nov * Journal: J Neurosci * Pages: 3594-3603 * Title: Inhibition of neurite outgrowth on astroglial scars in vitro. * Selected: true ---- * ID: 2243161 * Author: Schneider BF, Silver J. * Volume: 299 * Issue: 4 * Year: 1990 * Date: 1990 Sep 22 * Journal: J Comp Neurol * Pages: 462-469 * Title: Failure of the subcallosal sling to develop after embryonic X-irradiation is correlated with absence of the cavum septi. * Selected: true ---- * ID: 2141574 * Author: Snow DM, Lemmon V, Carrino DA, Caplan AI, Silver J. * Volume: 109 * Issue: 1 * Year: 1990 * Date: 1990 Jul * Journal: Exp Neurol * Pages: 111-130 * Title: Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. * Selected: true ---- * ID: 1694142 * Author: Siegal JD, Kliot M, Smith GM, Silver J. * Volume: 109 * Issue: 1 * Year: 1990 * Date: 1990 Jul * Journal: Exp Neurol * Pages: 90-97 * Title: A comparison of the regeneration potential of dorsal root fibers into gray or white matter of the adult rat spinal cord. * Selected: true ---- * ID: 1694141 * Author: Kliot M, Smith GM, Siegal JD, Silver J. * Volume: 109 * Issue: 1 * Year: 1990 * Date: 1990 Jul * Journal: Exp Neurol * Pages: 57-69 * Title: Astrocyte-polymer implants promote regeneration of dorsal root fibers into the adult mammalian spinal cord. * Selected: true ---- * ID: 2318341 * Author: Smith GM, Rutishauser U, Silver J, Miller RH. * Volume: 138 * Issue: 2 * Year: 1990 * Date: 1990 Apr * Journal: Dev Biol * Pages: 377-390 * Title: Maturation of astrocytes in vitro alters the extent and molecular basis of neurite outgrowth. * Selected: true ---- * ID: 1690673 * Author: Snow DM, Steindler DA, Silver J. * Volume: 138 * Issue: 2 * Year: 1990 * Date: 1990 Apr * Journal: Dev Biol * Pages: 359-376 * Title: Molecular and cellular characterization of the glial roof plate of the spinal cord and optic tectum: a possible role for a proteoglycan in the development of an axon barrier. * Selected: true ---- * ID: 2912745 * Author: Rudge JS, Smith GM, Silver J. * Volume: 103 * Issue: 1 * Year: 1989 * Date: 1989 Jan * Journal: Exp Neurol * Pages: 1-16 * Title: An in vitro model of wound healing in the CNS: analysis of cell reaction and interaction at different ages. * Selected: true ---- * ID: 3397407 * Author: Hankin MH, Silver J. * Volume: 272 * Issue: 2 * Year: 1988 * Date: 1988 Jun 8 * Journal: J Comp Neurol * Pages: 177-190 * Title: Development of intersecting CNS fiber tracts: the corpus callosum and its perforating fiber pathway. * Selected: true ---- * ID: 2456310 * Author: Hankin MH, Schneider BF, Silver J. * Volume: 272 * Issue: 2 * Year: 1988 * Date: 1988 Jun 8 * Journal: J Comp Neurol * Pages: 191-202 * Title: Death of the subcallosal glial sling is correlated with formation of the cavum septi pellucidi. * Selected: true ---- * ID: 3372729 * Author: Webster MJ, Shatz CJ, Kliot M, Silver J. * Volume: 269 * Issue: 4 * Year: 1988 * Date: 1988 Mar 22 * Journal: J Comp Neurol * Pages: 592-611 * Title: Abnormal pigmentation and unusual morphogenesis of the optic stalk may be correlated with retinal axon misguidance in embryonic Siamese cats. * Selected: true ---- * ID: 3653515 * Author: Holley JA, Silver J. * Volume: 123 * Issue: 2 * Year: 1987 * Date: 1987 Oct * Journal: Dev Biol * Pages: 375-388 * Title: Growth pattern of pioneering chick spinal cord axons. * Selected: true )# #template?query=Selected&key=Silver(publications.php|...)# #template?key=Silver(dokudata.php|...)# ~~NOTOC~~