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Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury.
J Neurosci Res. 2003 Oct 15; 74(2):221-6.JN

Abstract

We reported recently that overexpression of neurotrophin-3 (NT-3) by motoneurons in the spinal cord of rats will induce sprouting of corticospinal tract (CST) axons (Zhou et al. [2003] J. Neurosci. 23:1424-1431). We now report that overexpression of brain-derived neurotrophic factor (BDNF) or glial cell-derived neurotrophic factor (GDNF) in the rat sensorimotor cortex near the CST neuronal cell bodies together with overexpression of NT-3 in the lumbar spinal cord significantly increases axonal sprouting compared to that induced by NT-3 alone. Two weeks after unilaterally lesioning the CST at the level of the pyramids, we injected rats with saline or adenoviral vectors (Adv) carrying genes coding for BDNF (Adv.BDNF), GDNF (Adv.GDNF) or enhanced green fluorescent protein (Adv.EGFP) at six sites in the sensorimotor cortex, while delivering Adv.NT3 to motoneurons in each of these four groups on the lesioned side of the spinal cord by retrograde transport from the sciatic nerve. Four days later, biotinylated dextran amine (BDA) was injected into the sensorimotor cortex on the unlesioned side to mark CST axons in the spinal cord. Morphometric analysis of axonal sprouting 3 weeks after BDA injection showed that the number of CST axons crossing the midline in rats treated with Adv.BDNF or Adv.GDNF were 46% and 52% greater, respectively, than in rats treated with Adv.EGFP or PBS (P < 0.05). These data demonstrate that sustained local expression of neurotrophic factors in the sensorimotor cortex and spinal cord will promote increased axonal sprouting after spinal cord injury, providing a basis for continued development of neurotrophic factor therapy for central nervous system damage.

Authors+Show Affiliations

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14515351

Citation

Zhou, Lijun, and H David Shine. "Neurotrophic Factors Expressed in Both Cortex and Spinal Cord Induce Axonal Plasticity After Spinal Cord Injury." Journal of Neuroscience Research, vol. 74, no. 2, 2003, pp. 221-6.
Zhou L, Shine HD. Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury. J Neurosci Res. 2003;74(2):221-6.
Zhou, L., & Shine, H. D. (2003). Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury. Journal of Neuroscience Research, 74(2), 221-6.
Zhou L, Shine HD. Neurotrophic Factors Expressed in Both Cortex and Spinal Cord Induce Axonal Plasticity After Spinal Cord Injury. J Neurosci Res. 2003 Oct 15;74(2):221-6. PubMed PMID: 14515351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurotrophic factors expressed in both cortex and spinal cord induce axonal plasticity after spinal cord injury. AU - Zhou,Lijun, AU - Shine,H David, PY - 2003/9/30/pubmed PY - 2003/12/17/medline PY - 2003/9/30/entrez SP - 221 EP - 6 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 74 IS - 2 N2 - We reported recently that overexpression of neurotrophin-3 (NT-3) by motoneurons in the spinal cord of rats will induce sprouting of corticospinal tract (CST) axons (Zhou et al. [2003] J. Neurosci. 23:1424-1431). We now report that overexpression of brain-derived neurotrophic factor (BDNF) or glial cell-derived neurotrophic factor (GDNF) in the rat sensorimotor cortex near the CST neuronal cell bodies together with overexpression of NT-3 in the lumbar spinal cord significantly increases axonal sprouting compared to that induced by NT-3 alone. Two weeks after unilaterally lesioning the CST at the level of the pyramids, we injected rats with saline or adenoviral vectors (Adv) carrying genes coding for BDNF (Adv.BDNF), GDNF (Adv.GDNF) or enhanced green fluorescent protein (Adv.EGFP) at six sites in the sensorimotor cortex, while delivering Adv.NT3 to motoneurons in each of these four groups on the lesioned side of the spinal cord by retrograde transport from the sciatic nerve. Four days later, biotinylated dextran amine (BDA) was injected into the sensorimotor cortex on the unlesioned side to mark CST axons in the spinal cord. Morphometric analysis of axonal sprouting 3 weeks after BDA injection showed that the number of CST axons crossing the midline in rats treated with Adv.BDNF or Adv.GDNF were 46% and 52% greater, respectively, than in rats treated with Adv.EGFP or PBS (P < 0.05). These data demonstrate that sustained local expression of neurotrophic factors in the sensorimotor cortex and spinal cord will promote increased axonal sprouting after spinal cord injury, providing a basis for continued development of neurotrophic factor therapy for central nervous system damage. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/14515351/Neurotrophic_factors_expressed_in_both_cortex_and_spinal_cord_induce_axonal_plasticity_after_spinal_cord_injury_ L2 - https://doi.org/10.1002/jnr.10718 DB - PRIME DP - Unbound Medicine ER -