Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom

• Published in: PloS one 2013-05, Vol.8 (5), p.e63260
• Main Authors: Barbizan, Roberta, Castro, Mateus V, Rodrigues, Antônio C, Barraviera, Benedito, Ferreira, Rui S, Oliveira, Alexandre L R
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antisera; Apoptosis; Biology; Calcium-Binding Proteins - metabolism; Cell survival; Cytokines; Degeneration; Down-Regulation - drug effects; Female; Fibrin; Fibrin Tissue Adhesive - pharmacology; Fibrin Tissue Adhesive - therapeutic use; Functional plasticity; Gene expression; Gene regulation; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Glial plasticity; Immunohistochemistry; Inflammation; Ischemia; Laboratories; Microfilament Proteins - metabolism; Motor neurons; Motor Neurons - drug effects; Motor Neurons - pathology; Motor task performance; mRNA; Nerve Growth Factors - biosynthesis; Nerve Regeneration - drug effects; Nervous system; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - pathology; Neuronal-glial interactions; Neuroprotection; Neuroprotective Agents - pharmacology; Neurotrophic factors; Paralysis; Patient outcomes; Peripheral nervous system; Preservation; Pressure; Prosthesis Implantation; Radiculopathy - drug therapy; Radiculopathy - physiopathology; Rats; Rats, Inbred Lew; Receptors; Recovery; Recovery (Medical); Recovery of function; Recovery of Function - drug effects; Repair; Rodents; Sealing compounds; Snake Venoms - chemistry; Spinal cord; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal Cord - physiopathology; Spinal Nerve Roots - drug effects; Spinal Nerve Roots - pathology; Spinal Nerve Roots - physiopathology; Studies; Surgery; Survival; Synapses - drug effects; Synapses - pathology; Synaptophysin - metabolism; Transplants & implants; Trauma; Up-Regulation - drug effects; Venom; Venoms; Ventral roots; Wound Healing - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063260

Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a snake venom-derived fibrin sealant during surgical reconnection of avulsed roots at the spinal cord surface. The present work investigates the effects of this fibrin sealant on functional recovery, neuronal survival, synaptic plasticity, and glial reaction in the spinal motoneuron microenvironment after ventral root reimplantation. Female Lewis rats (7 weeks old) were subjected to VRA and root replantation. The animals were divided into two groups: 1) avulsion only and 2) replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera). Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group. In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the astroglial reaction and increased mRNA levels to neurotrophins and anti-inflammatory cytokines that may in turn, contribute to improving recovery of motor function.