PMID- 11532245
OWN - NLM
STAT- MEDLINE
DCOM- 20011212
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 913
IP  - 1
DP  - 2001 Sep 14
TI  - Subdural engraftment of serotonergic neurons following spinal hemisection 
      restores spinal serotonin, downregulates serotonin transporter, and increases 
      BDNF tissue content in rat.
PG  - 35-46
AB  - Spinal hemisection injury at T13 results in development of permanent mechanical 
      allodynia and thermal hyperalgesia due to interruption and subsequent loss of 
      descending inhibitory modulators such as serotonin (5-HT) and its transporter 
      (5-HT(T)). We hypothesize that lumbar transplantation of non-mitotic cells that 
      tonically secrete 5-HT and brain-derived neurotrophic factor (BDNF) will restore 
      alterations in 5-HT and 5-HT(T) systems within the spinal dorsal horn. We used an 
      immortalized rat neuronal cell line derived from E13 raphe (RN46A-B14) which is 
      shown to secrete 5-HT and BDNF in vitro and in vivo. Three groups (n=35) of 30 
      day old male Sprague-Dawley rats were spinally hemisected at T13 and 28 days 
      later received either lumbar RN46A-V1 control empty-vector (n=15) or RN46A-B14 
      (n=15) intrathecal grafts, or no transplant. Twenty-eight days following 
      transplantation, animals were perfused and tissue examined for changes in 5-HT, 
      5-HT(T), and BDNF at the site of transplantation or at lumbar enlargements (L5). 
      Immunohistochemistry revealed that RN46A-B14, but not RN46A-V1 cells, increased 
      5-HT tissue staining at L5 in the dorsal white matter as well as in superficial 
      dorsal horn laminae I and II on both ipsilateral and contralateral sides, results 
      confirmed by ELISA. Transplantation of RN46A-B14 cells significantly reduced 
      ipsilateral 5-HT(T), upregulated after injury. Significantly increased levels of 
      BDNF were also observed after RN46A-B14 transplantation but were not localized to 
      particular spinal laminae. These results are consistent with recovery of 
      locomotor function and reductions in chronic pain behaviors observed behaviorally 
      after RN46A-B14 transplantation and supports the pragmatic application of 
      cell-based therapies in correcting damaged circuitry after spinal cord injury.
FAU - Hains, B C
AU  - Hains BC
AD  - Department of Anatomy and Neurosciences, and Marine Biomedical Institute, 
      University of Texas Medical Branch, Galveston, TX 77555-1043, USA.
FAU - Fullwood, S D
AU  - Fullwood SD
FAU - Eaton, M J
AU  - Eaton MJ
FAU - Hulsebosch, C E
AU  - Hulsebosch CE
LA  - eng
GR  - NS11255/NS/NINDS NIH HHS/United States
GR  - NS39161/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain Tissue Transplantation/*methods
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cell Line, Transformed/metabolism/transplantation
MH  - Down-Regulation/*physiology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fetus
MH  - Functional Laterality/physiology
MH  - Immunohistochemistry
MH  - Male
MH  - Membrane Glycoproteins/*metabolism
MH  - *Membrane Transport Proteins
MH  - *Nerve Tissue Proteins
MH  - Neurons/metabolism/*transplantation
MH  - Raphe Nuclei/embryology/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Spinal Cord/metabolism/physiopathology/surgery
MH  - Spinal Cord Injuries/metabolism/physiopathology/*surgery
MH  - Subdural Space/surgery
MH  - Treatment Outcome
MH  - Up-Regulation/physiology
EDAT- 2001/09/05 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/05 10:00
PHST- 2001/09/05 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/05 10:00 [entrez]
AID - S0006-8993(01)02749-4 [pii]
AID - 10.1016/s0006-8993(01)02749-4 [doi]
PST - ppublish
SO  - Brain Res. 2001 Sep 14;913(1):35-46. doi: 10.1016/s0006-8993(01)02749-4.