Abstract:
:We investigated whether administration of neurotrophin-3 (NT-3) and NMDA-2D-expressing units, found previously to enhance transmission in neonatal rat spinal cord, strengthens synaptic connections in the injured neonatal cord. We employed electrophysiological methods to evaluate the strength of synaptic transmission to individual motoneurons in the contusion and staggered double hemisection spinal cord injury (SCI) models. SCI at caudal thoracic levels (T11-T12) was carried out at postnatal day 2 (P2). Plugs containing NT-3- secreting fibroblasts and NR2D-expressing HSV-1 amplicons (HSVnr2d) were implanted above the lesion. Control animals were treated with an amplicon-expressing beta-galactosidase (HSVlac). After 8-10 days of treatment, the rats were sacrificed and spinal cords were removed for intracellular recording. Untreated contused cords preserved a fraction of white matter and weak monosynaptic responses were observed through the injury region. However, no synaptic connections were observed in control cords receiving double hemisection injury. Combined treatment with NT-3 and HSVnr2d strengthened monosynaptic connections in contused cords and induced the appearance of weak but functional multisynaptic connections in double hemisected cords. In contrast, treatment with either NT-3 or HSVnr2d alone failed to induce appearance of synaptic responses through the hemisected region. These results suggest that chronic treatment with NT-3 secreting fibroblasts combined with facilitated function of NMDA receptors by HSVnr2d treatment strengthens connections that survive incomplete SCI and therefore that such combined treatment might facilitate recovery of function following SCI.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Arvanian VL,Bowers WJ,Anderson A,Horner PJ,Federoff HJ,Mendell LMdoi
10.1016/j.expneurol.2005.10.008keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
347-52issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(05)00356-0journal_volume
197pub_type
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