Axon growth across a lesion site along a preformed guidance pathway in the brain

Jin, Ying; Ziemba, Kristine S.; Smith, George M.

doi:10.1016/j.expneurol.2007.11.030

Cited by 22 publications

(20 citation statements)

References 48 publications

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“…However, only the animals receiving NGF gene-modified HiB5 cells showed significant reduction in hippocampal CA3 cell death (Philips et al, 2001). Transplanted DRG neurons can cross a lesion in the corpus callosum along a gradient pathway of NGF extending through the lesion (Jin et al, 2008). Similarly, transplantation of bone marrow stromal cells overexpressing BDNF attenuated neuronal injury in TBI models as indicated by improvement in behavioral recovery (Wang et al, 2013).…”

Section: Nt Treatments Enhance Neuronal Survival and Repair After Tramentioning

confidence: 99%

Neurotrophin treatment to promote regeneration after traumatic CNS injury

Kelamangalath

Smith

2013

Front. Biol.

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Neurotrophins are a family of growth factors that have been found to be central for the development and functional maintenance of the nervous system, participating in neurogenesis, neuronal survival, axonal growth, synaptogenesis and activity-dependent forms of synaptic plasticity. Trauma in the adult nervous system can disrupt the functional circuitry of neurons and result in severe functional deficits. The limitation of intrinsic growth capacity of adult nervous system and the presence of an inhospitable environment are the major hurdles for axonal regeneration of lesioned adult neurons. Neurotrophic factors have been shown to be excellent candidates in mediating neuronal repair and establishing functional circuitry via activating several growth signaling mechanisms including neuron-intrinsic regenerative programs. Here, we will review the effects of various neurotrophins in mediating recovery after injury to the adult spinal cord.

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Section: Nt Treatments Enhance Neuronal Survival and Repair After Tramentioning

confidence: 99%

Neurotrophin treatment to promote regeneration after traumatic CNS injury

Kelamangalath

Smith

2013

Front. Biol.

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“…NRP/GRP respond to a BDNF gradient by preferentially extending axons towards the source of BDNF (Bonner et al, 2010), indicating that graft derived axons can be specifically guided towards a chosen target. Furthering this concept, Smith and colleagues demonstrated that adult dorsal root ganglion (DRG) neurons transplanted into the corpus callosum would extend axons along a preformed pathway of NGF for the full length of the corpus callosum, even crossing a midline injury site (Jin et al, 2008). Later studies demonstrated that by combining NGF with a repulsive cue, semaphorin 3A (Sema 3A) DRG axons could be induced to make a 90° turn from the corpus callosum into the striatum (Ziemba et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Repair of spinal cord injury with neuronal relays: From fetal grafts to neural stem cells

Bonner

Steward

2015

Brain Research

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Spinal cord injury (SCI) disrupts the long axonal tracts of the spinal cord leading to devastating loss of function. Cell transplantation in the injured spinal cord has the potential to lead to recovery after SCI via a variety of mechanisms. One such strategy is the formation of neuronal relays between injured long tract axons and denervated neurons. The idea of creating a neuronal relay was first proposed over 25 years ago when fetal tissue was first successfully transplanted into the injured rodent spinal cord. Advances in labeling of grafted cells and the development of neural stem cell culturing techniques have improved the ability to create and refine such relays. Several recent studies have examined the ability to create a novel neuronal circuit between injured axons and denervated targets. This approach is an alternative to long-distance regeneration of damaged axons that may provide a meaningful degree of recovery without direct recreation of lost pathways. This brief review will examine the contribution of fetal grafting to current advances in neuronal grafting. Of particular interest will be the ability of transplanted neurons derived from fetal grafts, neural precursor cells and neural stem cells to reconnect long distance motor and sensory pathways of the injured spinal cord.

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“…Another molecule that acts as a chemoattractant guidance cue is netrin-1, which has recently been shown to have positive directional effects on neurite outgrowth from cultured dopaminergic neurons (Lin et al, 2005). To identify if these molecules alone or in combination would enhance the outgrowth of dopaminergic axons beyond that of GDNF, we used the corpus callosal model previously established in our laboratory (Jin et al, 2008, 2011, Ziemba et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Long distance directional growth of dopaminergic axons along pathways of netrin-1 and GDNF

Zhang

Jin

Ziemba

et al. 2013

Experimental Neurology

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Different experimental and clinical strategies have been used to promote survival of transplanted embryonic ventral mesencephalic (VM) neurons. However, few studies have focused on the long-distance growth of dopaminergic axons from VM transplants. The aim of this study is to identify some of the growth and guidance factors that support directed long-distance growth of dopaminergic axons from VM transplants. Lentivirus encoding either glial cell line-derived neurotrophic factor (GDNF) or netrin-1, or a combination of lenti-GDNF with either lenti-GDNF family receptor α1 (GFRα-1) or lenti-netrin-1 was injected to form a gradient along the corpus callosum. Two weeks later, a piece of embryonic day 14 VM tissue was transplanted into the corpus callosum adjacent to the low end of the gradient. Results showed that tyrosine hydroxylase (TH+) axons grew a very short distance from the VM transplants in control groups, with few axons reaching the midline. In GDNF or Netrin-1 expressing groups, more TH+ axons grew out of transplants and reached the midline. Pathways co-expressing GDNF with either GFRα-1 or netrin-1 showed significantly increased axonal outgrowth. Interestingly, only the GDNF/netrin-1 combination resulted in the majority of axons reaching the distal target (80%), whereas along the GDNF/GFRα-1 pathway only 20% of the axons leaving the transplant reached the distal target. This technique of long-distance axon guidance may prove to be a useful strategy in reconstructing damaged neuronal circuits, such as the nigrostriatal pathway in Parkinson’s disease.

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Axon growth across a lesion site along a preformed guidance pathway in the brain

Cited by 22 publications

References 48 publications

Neurotrophin treatment to promote regeneration after traumatic CNS injury

Neurotrophin treatment to promote regeneration after traumatic CNS injury

Repair of spinal cord injury with neuronal relays: From fetal grafts to neural stem cells

Long distance directional growth of dopaminergic axons along pathways of netrin-1 and GDNF

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