Table 1.
Summary of recent experiments assessing expression levels of neurotrophins and neurotrophin receptors after SCI.
| PMID | Reference | Molecule(s) | Injury model | Injury site | Sampling site | Experimental methods | Post injury time course | Findings | Notes |
|---|---|---|---|---|---|---|---|---|---|
| 10757326 | Hayashi et al. (2000) | NGF, BDNF, NT3, TrkA, TrkB, TrkC | Spinal cord crush (60 g, 1 s) | Under T10 vertebra | Five segments centered on epicenter | ISH | Six times; up to 3 days | Increase in BDNF and NT3, weaker increase for NGF; TrkA and TrkC not detected; TrkB detected in non-neurons and motoneurons, and increased in both with SCI | Functional status of animals was not assessed, but reference was given to Guth et al., 1994 (model shows mild motor deficit after awakening from anesthesia with apparent full recovery at 72 h); BDNF observed in non-neurons after SCI; qualitative data only, no statistics |
| qPCR (NGF only) | NGF increased weakly | ||||||||
| 11161589 | Liebl et al. (2001) | TrkA, TrkB, TrkC | 12.5 g cm NYU contusion | Under T9, T10 vertebra | Entire SC | ISH | 1 day | No difference in TrkA, TrkB, or TrkC expression rostral or caudal to injury | Absent Trk expression around injury site and reduced in penumbra, no statistics |
| 11331375 | Widenfalk et al. (2001) | NGF, BDNF, NT3, TrkA, TrkB, TrkC | 25 g cm NYU contusion transection | Under T9 vertebra | Cross-sections taken from regions throughout length of spinal cord injury epicenter and up to 1 cm caudal | ISH | Six times; up to 6 weeks | No change in TrkA, TrkB, TrkC; increase in NGF and BDNF up to 1 day, but no change vs. intact at 6 week; NT3 not detected in either intact or injured spinal cord | Functional status of animals with contusion was not assessed; reports on multiple injury types; statistical analysis uses optical density measures for ISH, and radioactivity for RPA |
| RPA (NGF, BDNF, NT3) | 6 weeks after contusion | No change in NGF and BDNF; NT3 not detected | |||||||
| 1 day after transection | Increase in NGF and BDNF; NT3 not detected | ||||||||
| 11358454 | Nakamura and Bregman (2001) | NGF, BDNF, NT3, NT4 | Lateral over hemisection | Under T6 vertebra | Entire SC | RPA | Five times; up to 2 weeks | Increase in NGF and BDNF up to 4 days, NT3 and NT4 not detected | Used whole SC mRNA, no assessment of injury or post-SCI function, expression data represented as % GAPDH |
| 12115676 | Qiao and Vizzard (2002) | TrkA, TrkB | Transection | Under T8-T10 vertebrae | L1-S1 DRG | IHC | 5–6 weeks | Increase in # of TrkA and TrkB positive cells in L1, L6/S1, no change at L4/5 | No assessment of post-SCI function, data expressed as # of Trk-IR positive cells |
| 15193526 | Gulino et al. (2004) | BDNF, NT4 | Lateral hemisection | Under T9 vertebra | L4/5 SC | IHC | Four times; up to 2 weeks | Decrease in BDNF, NT4 starting at 30 min, lasting up to 2 weeks | Coronal sections; no assessment of post-SCI function; data expressed as relative optical density of IR positive cells in ipsilateral vs. contralateral hemisected cord |
| 15236239 | Zvarova et al. (2004) | NGF, BDNF | Transection | Under T7–T9 vertebrae | T7-S1 | ELISA | <1, 6 weeks | Increase in NGF T7–T8 (rostral), and T13-L1, L6-S1 (caudal) 6 weeks post injury; Increase in NGF T9-T10 (caudal), and T13-L1, L6-S1 (caudal) < 1 week post injury; increase in BDNF T7-T10, T13-L1, L6-S1 6 weeks post injury; Increase in BDNF T7-L1, L3-S1 < 1 week post injury | No assessment of post-SCI function; neurotrophin concentration expressed as proportion of total protein |
| 15611995 | Qiao and Vizzard (2005) | TrkA, TrkB | Transection | Under T8-T10 vertebrae | L1-S1 DRG | IHC | 2 days and 2 weeks | Increase in # of TrkA and TrkB positive cells in L1, L6/S1, no change at L4/5 | No assessment of post-SCI function; data expressed as # of Trk-IR positive cells |
| 17055159 | Qin et al. (2006) | NGF, BDNF, NT3 | Lateral hemisection | Under T10 vertebra | Ventral horn caudal to T10 injury site | IHC | Three times; up to 3 weeks | Increase in # of BDNF, NT3, NGF positive cells in ventral horn | Characterized injuries by spared function (BBB locomotor score); data expressed as optical density of IR positive cells in hemisected cords relative to control cords |
| 17459471 | Li et al. (2007) | NGF, BDNF, NT3 | Transection | Under T9–T10 vertebra | Laminae I-IX, ∼1.5 cm caudal to injury site | IHC | Four times; up to 3 weeks | Increase in # of NGF IR cells and relative IR in laminae I-IX up to 3 weeks, # of NT3 IR cells and relative IR in laminae VIII and IX up to 3 weeks and laminae I–VII at 2 weeks, # of BDNF IR cells and relative IR in laminae I-IX up to 7 days | Characterized injuries by spared function (BBB locomotor score); data expressed as relative optical density of IR positive cells in hemisected vs. control cords |
| 18585435 | Hajebrahimi et al. (2008) | NGF, BDNF, NT3, TrkA, TrkB, TrkC | 25 g cm NYU contusion | Under T9-T10 vertebra | ∼1 cm block of SC | EthBr staining intensity | Eight times; up to 3 weeks | Decrease in NGF after 6 h that increases until 3 week where greater than control, BDNF and NT3 decrease after 6 h up to 3 weeks; TrkA, TrkB, TrkC decrease up to 3 weeks | B2m used as internal control; no assessment of injury or post-SCI function; data expressed as levels of mRNA relative to B2m |
| 21441969 | Qian et al. (2011) | TrkC | Transection/resection | Under T8–T9 vertebrae | Motor cortex; SC: adjacent to injury, rostral/caudal to injury | mRNA, protein | Four times; up to 2 weeks | Decrease at and around injury site from 1 to 7 days, then rapid increase until 14 days | mRNA more highly expressed at injury site than neighboring segments; protein shows same pattern; no assessment of post-SCI function |
| 22244304 | Keeler et al. (2012) | BDNF, NT4, NT3, TrkB, TrkC | Transection | Under T9 vertebra | L4–L6 SC (laser-captured motoneurons, select laminae); L4–6 DRG (large neurons) | Laser-capture, qPCR, WB | up to 31 days | Increase in NT4 and TrkB mRNA at 10 days, NT4 mRNA at 31 days; increase in NT3, NT4, BDNF protein at 31 days; increases in NT4 at 10 days, TrkB at 31 days in motoneurons; no change in expression in intermediate gray matter or large DRG neurons | More robust increase in expression after exercise; no assessment of post-SCI function; data expressed as mRNA or protein relative to control |
| Hougland et al. (this article) | NGF, BDNF, NT3, TrkA, TrkB, TrkC | 12.5 and 25 g cm NYU contusion | Under T9 vertebra | L4/5 spinal cord and DRG | qPCR | 6 and 12 weeks | Gene regulation differed by injury severity and by post-SCI time; correlated expression of genes at 12 weeks in DRG | Characterized injuries by spared function (BBB locomotor score) and by histology (white matter sparing); examined co-regulation of genes | |
Abbreviations: n.c, no change; IHC, immunohistochemistry; ISH, in situ hybridization; WB, western blot; RPA, ribonuclease protection assay; EthBr, ethidium bromide; LCM, laser-capture microdissection; qPCR, quantitative polymerase chain reaction; SC, spinal cord; DRG, dorsal root ganglion.