PMID- 12904464 OWN - NLM STAT- MEDLINE DCOM- 20030909 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 23 IP - 18 DP - 2003 Aug 6 TI - Synergistic effects of brain-derived neurotrophic factor and chondroitinase ABC on retinal fiber sprouting after denervation of the superior colliculus in adult rats. PG - 7034-44 AB - Damage to the adult CNS often causes devastating and permanent deficits because of the limited capacity of the brain for anatomical reorganization. The finding that collateral sprouting of uninjured fiber tracts mediates recovery of function prompts the search for experimental strategies that stimulate axonal plasticity after CNS trauma. Here we characterize treatments that promote the sprouting of undamaged retinal afferents into the denervated superior colliculus (SC) after a partial retinal lesion in the adult rat. Delivery of brain-derived neurotrophic factor (BDNF) was performed to enhance the intrinsic potential of retinal ganglion cells to reelongate their axons. Reduction of the neurite growth-inhibitory properties of the adult SC was accomplished via treatment with chondroitinase ABC (C-ABC), which degrades chondroitin sulfate proteoglycans. Retinal axons were labeled via intraocular injections of fluorescently tagged cholera toxin B subunit, and fiber sprouting within the denervated SC was measured by quantitative laser-scanning confocal microscopy 1 week after the retinal lesion. We found that both the administration of BDNF and the injection of C-ABC induce significant sprouting of retinal afferents into the collicular scotoma. Remarkably, the combined treatment with BDNF and C-ABC showed synergistic effects on axon growth. Colocalization analysis with anti-synapsin antibodies demonstrated synapse formation by the sprouting axons. These results suggest that the combined treatment with BDNF and C-ABC can be relevant in therapies for the repair of the damaged adult CNS. FAU - Tropea, Daniela AU - Tropea D AD - Istituto di Neuroscienze del Consiglio Nazionale delle Ricerche, and Scuola Normale Superiore, 56100 Pisa, Italy. FAU - Caleo, Matteo AU - Caleo M FAU - Maffei, Lamberto AU - Maffei L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chondroitin Sulfate Proteoglycans) RN - 9012-63-9 (Cholera Toxin) RN - EC 4.2.2.20 (Chondroitin ABC Lyase) SB - IM MH - Animals MH - Axons/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Count MH - Cholera Toxin MH - Chondroitin ABC Lyase/*pharmacology MH - Chondroitin Sulfate Proteoglycans/metabolism MH - Denervation MH - Drug Administration Routes MH - Drug Synergism MH - Microglia/metabolism/pathology MH - Nerve Fibers/drug effects MH - Rats MH - Rats, Long-Evans MH - Retina/cytology/*drug effects/*physiology MH - Retinal Ganglion Cells/drug effects/physiology MH - Scotoma/physiopathology MH - Superior Colliculi/drug effects/*physiology MH - Synapses/drug effects/physiology PMC - PMC6740661 EDAT- 2003/08/09 05:00 MHDA- 2003/09/10 05:00 PMCR- 2004/02/06 CRDT- 2003/08/09 05:00 PHST- 2003/08/09 05:00 [pubmed] PHST- 2003/09/10 05:00 [medline] PHST- 2003/08/09 05:00 [entrez] PHST- 2004/02/06 00:00 [pmc-release] AID - 23/18/7034 [pii] AID - 10.1523/JNEUROSCI.23-18-07034.2003 [doi] PST - ppublish SO - J Neurosci. 2003 Aug 6;23(18):7034-44. doi: 10.1523/JNEUROSCI.23-18-07034.2003.