Table 2.
Chondroitinase ABC
| Study | Animal model and injury model | Intervention and timing | Experimental group | Outcome: histologic/biochemical/physiological/behavioral |
|---|---|---|---|---|
| Fouad et al., 2009 | Model: adult female Fischer rats Injury: T8 transection, 1 mm spinal cord removed |
ChABC • 2 μL of 10 μg/mL SCs + OEG, 30 μL • In the lesion site in Mg-filled channel at 0 h PI |
SCI + • ChABC + SC + OEG in Mg channel (n = 8) • Mg channel alone (n = 7) No SCI + • Control (n = 4) |
Histologic/biochemical/physiological: Cell implantation and ChABC delivery prevented thickening of the bladder; prevented disorganization of αα-smooth muscle bundles, collagen (type III) deposition (at 14 wk) and reduced viscoelasticity in the bladder walls. • Sparse and fairly short serotonergic fibers in both treated and untreated cords. Behavioral: Cell implantation and ChABC delivery resulted in improvements in bladder function. |
| Carter et al., 2008 | Model: male and female YFP-H mice, 12 w, 20−25 g Injury: T12 crush with forceps to a depth of 0.5 mm |
ChABC • 6 μL of 10 U/mL, given ICV or IT Penicillinase, ICV or IT • 6 μL of 10 U/mL • Slow bolus injection at 0 h PI then on 2, 4, 6, 8, and 10 d PI |
SCI + • ChABC, ICV (n = 8) • ChABC, IT (n = 8) • Penicillinase, ICV (n = 8) • Penicillinase, IT (n = 8) • Control PI (n = 7) • Sham + ChABC (n = 4) • Sham + penicillinase (n = 4) • Sham (n = 11) |
Histologic/biochemical/physiological: ChABC given ICV or IT similarly degraded CSPGs at the site of injury. • ChABC promoted neuroprotection of corticospinal projection neurons and prevented cell atrophy by >50% in the cortical regions that contained CSNs projecting to the thoracic spinal cord. • ChABC led to robust sprouting at the lesion site (with possible retrograde protection of neuronal cell bodies). • ChABC significantly increased phosphorylation of ERK1 (p44 MAPK, but not p42 MAPK) at lesion site. Only intrathecal ChABC (but not IVC) ChABC increased PKC ββII and Akt expression. • No significant differences in GSK-3ββ expression or phosphorylation Behavioral: not reported |
| Xia et al., 2008 | Model: adult female SD rats, 250−300 g Injury: T9-10 lateral hemisection, 2 mm tissue removed |
ChABC • 6 μL of 10 U/mL Vimentin anti-sense cDNA in retrovirus • 6 μL, titer 3.9 × 108 cfu/mL • Starting on day of injury, direct infusion to lesion site; repeated every 2nd day for total of 8 infusions |
SCI + • ChABC • ChABC + vimentin anti-sense cDNA • Vimentin anti-sense cDNA • Saline or retrovisus without vimentin cDNA N ≥ 3/group |
Histologic/biochemical/physiological: ChABC and combined treatment (ChABC + vimentin anti-sense cDNA) greatly reduced CSPGs (CS-56) immunostaining in the scar at 2 wk PI, and reduced cystic cavity at 8 wk PI. • GFAP and vimentin expression was dramatically upregulated after SCI, especially in the scar tissue. Vimentin anti-sense, but not ChABC, reduced vimentin and GFAP expression at lesion site. Behavioral: not reported |
| Shields et al., 2008 | Model: adult female SD rats, 200−225 g Injury: C3 dorsal hemisection (laceration with Vibraknife, 1.5 mm deep) |
ChABC • 0.18 U in 6 μL (high dose) • 0.06 U in 6 μL (low dose) Penicillinase • 6 μL (30 μg/mL) • Starting on day of injury, direct infusion to lesion site; repeated every 2nd day for total of 5 infusions |
SCI + • ChABC high dose (n = 9) • ChABC low dose (n = 8) • Penicillinase (n = 5) 5-wk survival |
Histologic/biochemical/physiological: ChABC significantly enhanced the sensory axonal regeneration (number and length of axons) in a dose-dependent manner. Axons extended across the lesion gap and into the distal spinal cord stump in 2 of 8 (low dose) and in 3 of 9 (high dose) rats compared with none in the control group. • ChABC decreased CSPG, NG-2, and CS56 expression in a dose-dependent manner. The presence of CSPG cleaved products (2B6 immunoreactivity) was apparent in both ChABC-treated groups. • ChABC infusion did not influence laminin and GFAP immunoreactivity in the cord. Behavioral: not reported |
| Iseda et al., 2008 | Model: adult female SD rats, 10−12 wk old Injury: • T11 lateral hemisection • T11 contusion MASCIS impactor (10.0 g × 12.5 mm) |
ChABC • 3 μL of 1.125 U/μL in aCSF • 1 μL injected at the lesion site; 1 μL injected 2 mm rostrally and 2 mm caudally (injections 1 mm deep in the midline of the cord) • Within 1 h PI−acute • 1, 2, or 4 wk PI−delayed |
Hemisection SCI + • ChABC, acute • ChABC, 1, 2, or 4 wk delayed • aCSF Contusion SCI + • ChABC, 1 or 4 wk delayed • aCSF In total, 48 contused and 48 hemisected rats (but n/group not reported) |
Histologic/biochemical/physiological: compared the spinal cord contusion and hemisection models • Intraspinal injection of 3.375 U ChABC acutely or 1, 2, or 4 wk PI effectively eliminated CSPG to nearly undetectable levels in both hemisected and contused spinal cords from 4 d to 3 wk after treatment, with an increase of 2B6 immunoreactivity at the injured site (digested product of CSPG). • Many CST axons grew around the lesion site in hemisected cords after both acute and chronic ChABC treatment, but not in contused spinal cords. • Significant increases in GAP43 staining in the injury site vs. controls at 4 d, but no differences detected by 3 wk. • High dose of ChABC did not produce detectable changes in staining for GFAP in contusion model. Behavioral: not reported |
| Tom and Houlé, 2008 | Model: adult female SD rats, 225−250 g Injury: • Aspiration lesion of C5 right dorsal quadrant of ∼1 mm3 |
ChABC • 1 μL of 20 U/mL • Microinjection into the ventral spinal cord immediately rostral and caudal to C5 at 0 h PI, then on d 2 and 4 ChABC + PNG extending from C3 to C5 |
C5 SCI + • ChABC (n = 3) • Saline (n = 5) C5 SCI and PNG + • ChABC (n = 4) • Saline (n = 8) |
Histologic/biochemical/physiological: ChABC digested CSPG (based on 2B6 immunoreactivity) • Microinjections of ChABC did not affect the inflammatory response (ED1 + macrophages/microglia) at 5 d PI. • In the PNG experiment to assess regeneration, ChABC promoted significantly more axons to grow out of the graft and re-enter the spinal cord, extending at least 500 μm beyond the PNG-spinal cord interface. Behavioral: not reported |
| Iaci et al., 2007 | Model: adult female Long-Evan rats Injury: T9/10 forceps crush injury for 15 s (blade separation, 0.9 mm) |
ChABC • 0.06 U/rat per dose in 4 μL of aCSF Penicillinase 228 μg/mL in 4 μL aCSF • Intrathecal infusion just caudal to T9/10 at 0 h PI, then every 2nd d for up to 2 wk |
SCI + • ChABC • Penicillinase • aCSF Sacrificed on 1, 7, 14, 21 and 35 d, n = 3−5/time point |
Histologic/biochemical/physiological: ChABC intensively cleaved the GAG chains rostral and caudal to injury site; ChABC did not affect the NG2, neurocan, or phosphacan protein content and had a little impact upon NG-2 and neurocan mRNA. Hence, the effects of ChABC are likely due to removal of GAG chains but not a decrease in CPSG content. Behavioral: not reported |
| Vavrek et al., 2007 | Model: adult female Fisher rats Injury: T8 transection, 4 mm spinal cord removed |
ChABC • 2 μL of 10 μg/mL at 0 h PI, then every 2nd day for 4 wk SCs, 5 × 106 cells at 0 h PI in Mg-filled channel OEG, 105 cells into each stump at 0 h PI |
SCI + • ChABC + SCs in Mg channel + OEG (n = 5) • No treatment (n = 4) |
Histologic/biochemical/physiological: Treated rats had retrogradely FlouroGold-labeled cells in the reticulospinal nuclei, vestibular nuclei, and the raphe nucleus, as well as in the spinal cord. Cell numbers were highest in the thoracic spinal cord (T7-T8) and the lateral vestibular nucleus. • The animal with the largest bridge diameter also presented the largest number of regenerated cells. • Positive correlation was found between the number of regenerated cells and amount of ChABC digestion. • No labeled cells were present within the red nucleus, nor were they found in the sensorimotor cortex. • No retrogradely labeled cell bodies were found in the untreated group. Behavioral: not reported |
| Garcia-Alias et al., 2008 | Model: Lister hooded rats, 250−300 g Injury: C4 dorsal column crush (forceps compression × 20 s) |
ChABC • 6 μL at 100 U/mL = 0.6 U, injection via cannula into the right lateral ventricle, given 0 h PI, or at 2, 4, or 7 d, then q48h for total of 7 applications |
SCI + • ChABC • Control SCI N = 6/group |
Histologic/biochemical/physiological: With CST anterograde tracing, all ChABC groups had less dieback and more axonal growth than did control group, but the statistics are not reported. Behavioral: Staircase pellet retrieval task (no. and %): effect only in the acute ChABC at 42 d PI (p < 0.05). Grip strength: no difference among groups. Placing response: all ChABC groups better than control (p < 0.05). Forepaw stride length: all ChABC groups better than control at 42 d PI (p < 0.05) |
| Massey et al., 2008 | Model: male SD rats, 275−350 g Injury: T1 dorsal column crush (forceps compression × 10 s) |
ChABC • 690 nL at 20 U/mL NT-3 lentivirus • Microinjection 0.3 mm deep to the lateral junction of the right fasciculus gracilus and the right nucleus gracilis • ChABC given 0 h PI, NT-3 given 12 d PI |
SCI + • ChABC + NT-3 (n = 6) • ChABC (n = 4) • NT-3 (n = 5) • Vehicle n = 6) |
Histologic/biochemical/physiological: Regeneration into gracile nucleus of GFP-labeled DRG implanted rostral to lesion site 14 d PI. Control, 336.95 μm +/− 140.96; ChABC, 1276.2 μm +/− 243.5, p < 0.05; NT-3, 1118.5 μm +/− 219.8, p < 0.01; ChABC + NT-3, 10,820.3 μm +/− 2583.5, p < 0.001. Behavioral: not reported |
| Tester and Howland, 2008 | Model: adult female cat Injury: T10 hemisection |
ChABC • 0.025 U, via gelfoam placed in lesion site at 0 h PI for 30 min, then q48h for 1 mo via port tubing sutured to muscle |
SCI + • ChABC (n = 3) • Deactivated ChABC (n = 2) • Port placement + saline (n = 1) • Control SCI (n = 3) |
Histologic/biochemical/physiological: Sprouting of 5-HT fibers into the rostral portion of the lesion showed a trend (p = 0.08) for greater numbers in the ChABC group. Behavioral: Plantar stepping: no difference of onset of recovery Ladder, pegboard, narrow beam: quicker rate of recovery in the ChABC group (p < 0.05). On pegboard at 16 and 20 wk PI, ChABC were better than controls. |
| Barritt et al., 2006 | Model: male Wistar rats, 220−250 g Injury: C4 dorsal column crush |
ChABC • 6 μL at 10 U/mL = 0.060 U, intrathecal bolus injections delivered via a flexible Silastic catheter inserted subdurally at the C4 level and pushed 8 mm, given at 0 h PI, then q48h for 10 d |
SCI + • ChABC • SCI control No SCI + • ChABC • control N = 16/group |
Histologic/biochemical/physiological: In anterograde CST tracing, ChABC group produced increased sprouting proximal to the lesion site, and distal to injury site at C5 (p < 0.05), but not C6. ChABC elicited increased 5HT sprouting caudal to the injury in the ventral horn (p < 0.05). Behavioral: No difference in thermal or mechanical stimuli among the groups. However, the injured animals did not develop thermal hyperalgesia or mechanical allodynia. |
| Houle et al., 2006 | Model: female SD rats, 225−250 g Injury: C3 hemisection |
ChABC • 0.005 U at 0 h PI, then 0.011 U/d for 7 d via an osmotic minipump and cannula |
SCI + • PNG transplant + ChABC (n = 7) • PNG transplant (n = 5) |
Histologic/biochemical/physiological: In rubrospinal anterograde tracing, mean length of axons entering spinal cord from PNG: control PNG = 11.5 +/− 5.3 mm, PNG + ChABC = 1271.6 +/− 48.5 mm (p < 0.01) Behavioral: Rearing cylinder–no statistical effect. Rope ladder–no quantifiable difference. Grooming task: control, 1.6; ChABC, 2.86 (p < 0.05) |
| Huang et al., 2006 | Model: Female SD Rats 250−300 g Injury: T8 Transection |
ChABC • 6 μL at 1 U/mL = 0.006 U, or at 5 U/mL = 0.030 U, infusion via catheter placed in the epidural space from C1 down to T8 level, at 0 h PI, then q48h for 2 wk |
SCI + • ChABC • Tube • Saline • Control SCI N = 4/group |
Histologic/biochemical/physiological: In anterograde CST tracing, only the 1 U/mL (0.006 U) ChABC group was reported to induce growth across lesion site (but not quantified). Large cysts were found in the 5 U/mL (0.030 U) ChABC group. Behavioral: BBB: ChABC at the dose of 1 U/mL (0.006 U) had higher scores compared to controls (peak BBB in control ∼2.7, ChABC ∼6). No effect with 5 U/mL (0.030 U) of ChABC |
| Kim et al., 2006 | Model: female SD rats, 200−250 g Injury: C4 over hemisection |
ChABC • 0.2 U delivered to injury site via gelfoam at 0 h PI, then at 3, 7, and 11 d via intrathecal injections |
SCI + • ChABC (n = 7) • Fetal spinal cord transplant + ChABC (n = 18) • Fetal spinal cord transplant (n = 19) • Control SCI (n = 7) |
Histologic/biochemical/physiological: In anterograde CST tracing, no effect in any group. 5HT staining in the ventral gray matter distal (C6/7) to the injury site improved only in the transplant + ChABC group (45.2%) compared to control (21.7%, p < 0.05). ChABC (26.3%), transplant (30.4%). Behavioral: Gridwalk: no effect of ChABC, but there was an effect of transplant + ChABC (p < 0.01). With rearing cylinder, no effect in any group, but “functional touching” in the cylinder and tape removal were improved only in the transplant + ChABC group. |
| Massey et al., 2006 | Model: male SD rats, 250–300 g Injury: C6/7 quadsection |
ChABC • 1 μL at 50 U/mL = 0.050 U, right medulla microinjection at 0.3−0.5 mm below the dorsal pial surface and just lateral to the cuneate nucleus, given at 0 h PI |
SCI + • ChABC (n = 6) • Vehicle to cuneate nucleus of medulla (n = 5) |
Histologic/biochemical/physiological: CTB-labeled sensory fibers in the brainstem. The ChABC group had significantly more labeling (p < 0.01) (control 165.41 +/− 67.73, ChABC 323.73 +/− 69.53). Microelectrode recording from cuneate nucleus: significantly more sites responding to forelimb stimulation in ChABC group (p < 0.001) (control = 46.3% +/− 3.3, ChABC 74.5% +/− 4.8) Behavioral: not reported |
| Tan et al., 2006 | Model: female SD rats, 175–200 g Injury: T8 dorsal bilateral transaction, lesion extended ventrally to the depth of the central canal (∼1.5 mm) |
Anti-NG2 MAbs • 50 μL of neutralizing or non-neutralizing anti-NG2 MAbs, via gelfoam at injury site ChABC • 10 μL of 2.5 U/mL, via gelfoam at injury site, given at 0 h PI |
SCI + • Anti-NG2 MAbs (n = 7) • Non-neutralizing anti-NG2 MAbs (n = 5) • Conditioning treatment + anti-NG2 MAbs (n = 7) • Conditioning treatment + non-neutralizing anti-NG2 MAbs (n = 7) • ChABC (n = 6) • Penicillinase control (n = 3) |
Histologic/biochemical/physiological: In animals treated with the neutralizing anti-NG-2 antibodies, labeled axons penetrated the caudal border of the lesion and grew into and beyond the lesion center. Combining a conditioning treatment with NG-2 MAbs resulted in sensory axon regeneration past the glial scar and into the white matter rostral to the injury site. The combinatorial approach neutralized extrinsic inhibition and increased intrinsic growth results in anatomically correct axon regeneration, a prerequisite for functional recovery. Behavioral: not reported |
| Caggiano et al., 2005 | Model: female Long-Evans rats Injury: T9/10 mild, moderate, and severe forcep compression injury |
ChABC • 0.06 U, delivered intrathecally using a mechanical syringe, 10 min PI, then q48h for 2 wk |
SCI + • Mild ChABC (n = 13) • Moderate ChABC (n = 15) • Severe ChABC (n = 7) • Mild control (n = 14) • Moderate control (n = 15) • Severe aCSF control (n = 5) • Severe control (n = 6) |
Histologic/biochemical/physiological: not reported Behavioral: BBB: ChABC (peak, 9.1 +/− 0.64) improved scores in moderate injury (control peak BBB, 6.85 +/− 0.48), p < 0.05 from 21 d PI onward (except d 42 and 49) and severe injury control (peak BBB, 3.67–4.0 +/− 1.2–0.87), ChABC (7.5 +/− 1.43), p < 0.05 at 28, 49, and 63 d PI, (but not at 35, 42, 56, 70, or 77). No effect on mild injury (control, 9.7 +/− 0.63, ChABC, 9.9 +/− 0.5). Bladder: Reduced residual volume in the ChABC group in the moderate injury (but not in the other two injury models). |
| Fouad et al., 2005 | Model: female Fischer rats 165−180 g Injury: T8 complete transection |
ChABC • 2 μL at 10 U/mL = 0.02 U, + Mg bridge + SCs and rostrocaudal OEC grafts, delivery via a minipump, given at 0 h PI, then q48h for 4 wk |
SCI + • Mg bridge + SC and rostrocaudal OEC grafts (n = 6) • Mg bridge + SCs and rostrocaudal OEC grafts + ChABC (n = 5) • Mg bridge (control, n = 8) |
Histologic/biochemical/physiological: 5-HT fibers distal to lesion were higher in the transplant + ChABC than control, but no correlation between 5-HT and behavior. Corticospinal and medial reticular formation: Only a few axons entered the graft and none were observed caudal to graft–no difference between groups. Number of myelinated axons in the bridge was significantly higher in the transplant + ChABC. Myelinated axons in bridge correlated with BBB (r = 0.63). Behavioral: BBB: The transplant + ChABC had higher scores than the other two groups at 8 and 9 wk PI. Von Frey hair stimulation at base of tail: Both transplant and transplant + ChABC had lower thresholds. |
| Ikegami et al., 2005 | Model: female SD rats, 230−250 g Injury: T10 NYU impactor (10 g × 25 mm) |
ChABC • 12 mL at 200 U/mL = 2.4 U/d + NPSC + Infusion via minipump with the tip of the silicon tube placed just caudal to the level of injury (vertebral T11), continuously from 0 h PI for 2 wk, NPSC transplanted 1 wk after injury |
SCI + • NPSC + ChABC (n = 14) • NPSC + inactivated ChABC (n = 7) • inactivated ChABC (n = 5) |
Histologic/biochemical/physiological: NPSC migration: ChABC was reported (pictures displayed) to promote greater migration of NPSC into the host tissue (not quantified). Total GAP-43 positive fibers in the lesion center revealed differences among the groups (p < 0.05): control ∼200; NPSC ∼500; ChABC + NPSC ∼1400. Behavioral: not reported |
| Chau et al., 2004 | Model: female Fischer rats Injury: T8 hemisection |
ChABC • 0.06 U/d with SC-seeded guidance channels, intrathecal infusion via minipump from 0 h PI to ∼d 16 |
SCI + • 3 mm SC/Mg mini-channel + ChABC • 3 mm SC/Mg mini-channel N = 12/group |
Histologic/biochemical/physiological: In anterograde tracing, control animals displayed no growth caudal to mini-channel. ChABC group: 7/12 animals displayed growth caudal to mini-channel with the mean axonal growth in the 7 animals being 3.18 mm +/− 0.98 (other 5 not included). Number of myelinated axons in the channel was higher in the ChABC group (p < 0.002, n = 5; control ∼450, ChABC ∼1550). Cavitation was reduced in the ChABC group (p < 0.02, n = 3). Behavioral: not reported |
| Yick et al., 2004 | Model: SD rat 200−250 g Injury: C7 right hemisection |
ChABC • 10 μL of 2.5 U/mL = 0.025 U via soaked gelfoam placed on top of lesion site, at 0 h PI Lithium chloride IP • 85 mg/kg (correct dose in erratum), daily |
SCI + • ChABC • Lithium • Lithium + ChABC • PBS N = 4/group for behavioral analysis, Western blotting, and immunohistochemistry N = 5/group for axonal tracing |
Histologic/biochemical/physiological: Retrograde tracing (Fluoro-gold) of rubrospinal neurons. Lithium–no effect, ChABC (22.1 % +/− 4.6) better than control (2.3% +/− 0.9, p < 0.001); lithium + ChABC (41.5% +/− 4.6) better than ChABC and control (p < 0.001). Behavioral: Forelimb use in cylinder: lithium (18.1%, +/− 3.7)–no effect; ChABC group (29.1% +/− 1.9) better than control (7.7% +/− 3.0, p < 0.01). Lithium + ChABC (38.7% +/− 5.2) better than control (p < 0.01) and ChABC (p < 0.05). |
| Yick et al., 2003 | Model: female SD rats, 9 wk old Injury: T11 hemisection |
ChABC • 10 μL of 2.5 U/mL = 0.025 U via soaked gelfoam placed on top of lesion site, at 0 h PI |
SCI + • ChABC Sham N = 6/group |
Histologic/biochemical/physiological: C7 retrograde labeling of L1 Clarke's neurons at 4 wk PI: ChABC, 12.3% +/− ∼1.5; control 0. Behavioral: not reported |
| Bradbury, Nature, 2002 | Model: Adult Male Wister rat Injury: C4 dorsal column crush |
ChABC • 6 μl at 10U/ml = 0.06 U Bolus injections through an intrathecal silastic catheter with the tip just rostral to the SCI. • injections began @ Oh PI, then every 2nd day for 10 days |
1. SCI + ChABC (n = 12 + 5) 2. SCI control (n = 12 + 9) 3. Sham (n = 12 + 8) (anatomical/e-phys + behavioral analysis) |
Histologic / Biochemical / Physiological: ChABC Improved CST growth/sprouting 2 mm proximal thru 1 mm distal to lesion (but not 2 - 5 mm distal) p < 0.05. Behavioral: ChABC group improved; Beam walk 2-6 weeks; Grid walk 2-6 weeks, Stride length, Stride width. No effect on the sensory test of tape removal. Electrophysiology postsynaptic potentials were better in the ChABC group 1 - 7 mm distal to lesion (p < 0.001) |
| Yick, NeuroReport, 2000 | Model: Female SD Rats 200 - 250 g; Injury: T11 hemisection |
ChABC • 10 μl of ChABC at 1.0 U/ml = 0.010 U 2.5 U/ml = 0.025 U 5.0 U/ml = 0.050 U Soaked gelfoam placed on top of implanation site @ Oh PI |
1. SCI + Peripheral nerve graft (PNG) + 1.0 U/ml ChABC (n = 6) 2. SCI + PNG + 2.5 U/ml ChABC (n = 8) 3. SCI + PNG + 5.0 U/ml ChABC (n = 6) 4. SCI + PNG + BDNF (n = 3) 5. SCI + PNG + vehicle (n = 6) 6. Control SCI + PNG (n = 6) |
Histologic / Biochemical / Physiological: counting of Fluoro-Gold retrogradely labeled Clarke neurons reveals 5.8% with 1.0 U/ml ChABC, 2.0% with 2.5 U/ml ChABC, and 12.8% with 5.0 U/ml ChABC. No retrogradely labeled cells with BDNF, Vehicle, or PNG alone. Behavioral: Not tested |
aCSF, artificial cerebrospinal fluid; BBB, Basso, Beattie and Bresnahan locomotor test; BMS, Basso Mouse Scale; C5, cervical vertebra 5; ChABC, chondroitinase ABC; CSPG, chondroitin sulfate proteoglycan; CST, corticospinal tract; CTB labeled, cholera toxin subunit B; DREZ, dorsal root entry zone; GAG, glycosaminoglycan; GAP, growth-associated protein; GSK-3ββ, glycogen synthase kinase-3ββ; GFAP, glial fibrillary acidic protein; ICV, intracerebroventricularly; IT, intrathecally; MAb, monoclonal antibody; Mg, Matrigel; NT-3, Neurotrophin-3; NPSC, neural precursor cells; OEG, olfactory-ensheathing glia; PI, post-injury; PNG, peripheral nerve graft; q48h, interval 48 hours; SC, Schwann cell; SCI: spinal cord injury; SD rats, Sprague-Dawley rats; T8, thoracic vertebra 8; YFP-H, yellow fluorescent protein.