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Reinnervation of the rat musculocutaneous nerve stump after its direct reconnection with the C5 spinal cord segment by the nerve graft following avulsion of the ventral spinal roots: a comparison of intrathecal administration of brain-derived neurotrophic factor and Cerebrolysin

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Abstract

Experimental model based on the C5 ventral root avulsion was used to evaluate the efficacy of brain-derived neurotrophic factor (BDNF) and Cerebrolysin treatment on motor neuron maintenance and survival resulted in the functional reinnervation of the nerve stump. In contrast to vehicle, BDNF treatment reduced the loss and atrophy of motor neurons and enhanced the regrowth axon sprouts into the distal stump of musculocutaneous nerve. However, the axon diameter of the myelinated fibers was smaller than those of control rats. The morphometric results were related to a low score in behavioral test similar to vehicle-treated rats. Cerebrolysin treatment greatly protected the motor neurons against cell death. Moreover, morphometric features of myelinated axons were better than those of rats treated with vehicle or BDNF. The mean score of grooming test suggested better results of the functional motor reinnervation than after BDNF administration. The majority of rescued motor neurons regenerating their axons through nerve graft in both BDNF- and Cerebrolysin-treated rats expressed choline acetyltransferase immunostaining. The results demonstrate that BDNF has more modest effects in preventing the death of motor neurons and functional recovery of injured motor nerve after root avulsion than Cerebrolysin.

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References

  • Akai F, Hiruma S, Sato T, Iwamoto N, Fujimoto M, Ioku M, Hashimoto S (1992) Neurotrophic factor like effect of FPF1070 on septal cholinergic neurons after transection of fimbria-fornix in the rat brain. Histol Histopathol 7:213–221

    CAS  PubMed  Google Scholar 

  • Bertelli JA, Mira JC (1993) Behavioral evaluating methods in the objective clinical assessment of motor function after experimental brachial plexus reconstruction in the rat. J Neurosci Methods 46:203–208

    Article  CAS  PubMed  Google Scholar 

  • Bertelli JA, Mira JC (1995) The grasping test: a simple behavioral method for objective quantitative assessment of peripheral nerve regeneration in the rat. J Neurosci Methods 58:1–2

    Article  PubMed  Google Scholar 

  • Bowe CM, Evans NH, Vlacha V (1992) Progressive morphological abnormalities observed in rat spinal motor neurons at extended intervals after axonal regeneration. J Comp Neurol 321:576–590

    CAS  PubMed  Google Scholar 

  • Cao X, Shoichet MS (2003) Investigating the synergistic effect of combined neurotrophic factor concentracion gradients to guide axonal growth. Neuroscience 122:381–389

    Article  CAS  PubMed  Google Scholar 

  • Carlstedt T, Linda H, Cullheim S, Risling M (1986) Reinnervation of hind limb muscles after ventral root avulsion and implantation in the lumbar spinal cord. Acta Physiol Scand 128:645–646

    CAS  PubMed  Google Scholar 

  • Carlstedt T, Grane P, Hallin RG, Norén G (1995) Return of function after spinal cord implantation of avulsed spinal nerve roots. Lancet 346:1323–1325

    Article  CAS  PubMed  Google Scholar 

  • Chiu AY, Chen EW, Loera S (1994) Distinct neurotrophic responses of axotomized motor neurons to BDNF and CNTF in adult rats. Neuroreport 5:693–696

    CAS  PubMed  Google Scholar 

  • Clatterbuck RE, Price DL, Koliatsos VE (1994) Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons. J Comp Neurol 342:45–56

    CAS  PubMed  Google Scholar 

  • Cruz R, Francis L, Diaz-Suarez CM, Gonzalez-Fraguela ME (1998) Short-term effects of septo-hippocampal pathway transection and Cerebrolysin effects on glutathione-related enzymes in the rat brain. Rev Neurol (Paris) 26:551–554

    Google Scholar 

  • De Medinaceli L (1995) Interpreting nerve morphometry data after experimental traumatic lesions. J Neurosci Methods 58:29–37

    Article  PubMed  Google Scholar 

  • Friedman B, Kleinfeld D, Ip NY, Verge VM, Moulton R, Boland P, Zlotchenko E, Lindsay RM, Liu L (1995) BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons. J Neurosci 15:1044–1056

    CAS  PubMed  Google Scholar 

  • Gillespie MJ, Stein RB (1983) The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves. Brain Res 259:41–56

    Article  CAS  PubMed  Google Scholar 

  • Haninec P, Dubový P, Houšt’ava L, Stejskal L (1996) Alternative methods of the brachial plexus reconstruction-An experimental study. Scripta Med 69:221–226

    Google Scholar 

  • Haninec P, Dubový P, Houšt’ava L, Stejskal L (1997) Reconstructive operations of brachial plexus injury and the experimental model of their management. Intern Proc Div, Centennial perspective. Monduzzi, Amsterdam, pp 2103–2107

  • Haninec P, Dubový P, Houšt’ava L, Stejskal L (2000) Acellular nerve graft re-seeded by Schwann cells migrating from the nerve stump can stimulate spinal motor neurons for functional reinnervation of the rat muscle. Ann Anat 182:123–131

    CAS  Google Scholar 

  • Haninec P, Houšt’ava L, Stejskal L, Dubový P (2003) Rescue of rat spinal motor neurons from avulsion-induced cell death by intrathecal administration of IGF-I and Cerebrolysin. Ann Anat 185:233–238

    CAS  PubMed  Google Scholar 

  • Heumann R (1994) Neurotrophin signaling. Curr Opin Neurobiol 4:668–679

    Article  CAS  PubMed  Google Scholar 

  • Horvat JC, Pecot-Deachavassine M, Mira JC (1988) Functional reinnervation of a denervated skeletal muscle of the adult rat by axons regenerating from the spinal cord through a peripheral nervous system graft. Progr Brain Res 78:219–224

    CAS  Google Scholar 

  • Hutter-Paier B, Steiner E, Windisch M (1998) Cerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia. J Neural Transm 53:351–361

    CAS  Google Scholar 

  • Kishino A, Ishige Y, Tatsuno T, Nakayama C, Noguchi H (1997) BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth. Exp Neurol 144:273–286

    Article  CAS  PubMed  Google Scholar 

  • Klocker N, Kermer P, Weishaupt JH, Labes M, Ankerhold R, Bahr M (2000) Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inositol-3′-kinase/protein kinase B signaling. J Neurosci 20:6962–6967

    CAS  PubMed  Google Scholar 

  • Koliatsos VE, Applegate MD, Kitt CA, Walker LC, DeLong MR, Price DL (1989) Aberrant phosphorylation of neurofilaments accompanies transmitter-related changes in rat septal neurons following transection of the fimbria-fornix. Brain Res 482:205–218

    Article  CAS  PubMed  Google Scholar 

  • Koliatsos VE, Price WL, Pardo CA, Price DL (1994) Ventral root avulsion-an experimental model of death of adult motor neurons. J Comp Neurol 342:35–44

    CAS  PubMed  Google Scholar 

  • Li L, Oppenheim RW, Lei M, Houenou J (1994) Neurotrophic agents prevent motor neuron death following sciatic nerve section in the neonatal mouse. J Neurobiol 25:759–766

    CAS  PubMed  Google Scholar 

  • Li LX, Wu WT, Lin LFH, Lei M, Oppenheim RW, Houenou LJ (1995) Rescue of adult mouse motor neurons from injury-induced cell death by glial cell line-derived neurotrophic factor. Proc Natl Acad Sci USA 92:9771–9775

    CAS  PubMed  Google Scholar 

  • Mitsumoto H, Ikeda K, Klinkosz B, Cedarbaum JM, Wong V, Lindsay RM (1994) Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 265:1107–1110

    CAS  PubMed  Google Scholar 

  • Murray M, Kim D, Liu Y, Tobias C, Tessler A, Fischer I (2002) Transplantation of genetically modified cells contributes to repair and recovery from spinal injury. Brain Res Brain Res Rev 40:292–300

    Article  PubMed  Google Scholar 

  • Novikov L, Novikova L, Kellerth JO (1995) Brain-derived neurotrophic factor promotes survival and blocks nitric oxide synthase expression in adult rat spinal motor neurons after ventral root avulsion. Neurosci Lett 200:45–48

    Article  CAS  PubMed  Google Scholar 

  • Oppenheim RW (1996) Neurotrophic survival molecules for motor neurons: an embarrassment of riches. Neuron 17:195–197

    Article  CAS  PubMed  Google Scholar 

  • Oppenheim RW, Prevette D, Haverkamp LJ, Houenou L, Yin QW, McManaman J (1993) Biological studies of a putative avian muscle-derived neurotrophic factor that prevents naturally occurring motor neuron death in vivo. J Neurobiol 24:1065–1079

    CAS  PubMed  Google Scholar 

  • Ruther E, Ritter R, Apecechea M, Freytag S, Windish M (1994) Efficacy of peptidergic nootropic drug Cerebrolysin in patients with senile dementia of Alzheimer type. Pharmacopsychiatry 27:32–40

    CAS  PubMed  Google Scholar 

  • Satou T, Imano M, Akai F, Hashimoto S, Itoh T, Fujimoto M (1993) Morphological observation of effects of Cerebrolysin on cultured neuronal cells. In: Nicolini, Zatta, Coraine (eds) Alzheimer’s disease and related disorders. Pergamon, Oxford, pp 195–196

  • Segal RA, Greenberg ME (1996) Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 19:463–489

    Google Scholar 

  • Shibata M, Murray M, Tessler A, Ljubetic C, Connors T, Saavedra RA (2000) Single injections of a DNA plasmid that contains the human Bcl-2 gene prevent loss and atrophy of distinct neuronal populations after spinal cord injury. Neurorehabil Neural Repair 14:319–330

    CAS  PubMed  Google Scholar 

  • Sugita Y, Kondo T, Kanazawa A, Itou T, Mizuno Y (1993) Protective effect of FPF 1070 (Cerebrolysin) on delayed neuronal death in the gerbil-detection of hydroxyl radicals with salicylic acid. No To Shinkei 45:325–331

    CAS  PubMed  Google Scholar 

  • Windisch M, Gschanes A, Hutter-Paier B (1998) Neurotrophic activities and therapeutic experience with a brain derived peptide preparation. J Neural Transm 53:289–298

    CAS  Google Scholar 

  • Wu W (1993) Expression of nitric-oxide synthase (NOS) in injured CNS neurons as shown by NADPH diaphorase histochemistry. Exp Neurol 120:153–159

    Article  CAS  PubMed  Google Scholar 

  • Wu W (1996) Potential roles of gene expression change in adult rat spinal motor neurons following axonal injury: a comparison among c-jun, low-affinity nerve growth factor receptor (LNGFR), and nitric oxide synthase (NOS). Exp Neurol 141:190–200

    Article  CAS  PubMed  Google Scholar 

  • Yan Q, Elliott J, Snider WD (1992) Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360:755–777

    Article  PubMed  Google Scholar 

  • Zamboni L, De Martino C (1967) Buffered picric acid-formaldehyde: a new, rapid fixative for electron microscopy. J Cell Biol 35:14

    Google Scholar 

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Acknowledgements

We thank Ms. Dana Kutějová for her skillful technical assistance. This work was supported by grants NF/6658-3 (the Ministry of Health of the Czech Republic), and CEZ: J07/98:141100001 (the Ministry of Education of the Czech Republic).

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Correspondence to P. Dubový.

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Haninec, P., Dubový, P., Šámal, F. et al. Reinnervation of the rat musculocutaneous nerve stump after its direct reconnection with the C5 spinal cord segment by the nerve graft following avulsion of the ventral spinal roots: a comparison of intrathecal administration of brain-derived neurotrophic factor and Cerebrolysin. Exp Brain Res 159, 425–432 (2004). https://doi.org/10.1007/s00221-004-1969-z

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