Table 11.
Polyethylene glycol
| Paper | Animal model and injury model | Intervention and timing | Experimental groups |
Reported outcomes: • Histologic/biochemical/physiological • Behavioral |
|---|---|---|---|---|
| Baptiste J Neuropathol Exp Neurol 2009 |
Model: Female Wistar rats 200–250g Injury: C8 Extradural Clip Compression35g × 1 min |
PEG IV • 1 g/kg @ 1h PI (for animals surviving < 24hr) • 1 g/kg @ 1h & 3 h PI (for animals surviving > 24hr) (PEG: 2,000 Da, 30%w/w in sterile lactate Ringer's (SLR)) |
SCI + • PEG (n = 14) • SLR (n = 14)Sham (n = 14)(for TUNEL/immunos 7d PI and Western blots at 2,4,8 24h PI) SCI + • PEG (n = 12) • SLR (n = 11)Sham (n = 9) (for long term survival 42d PI) |
Histologic/Biochemical/Physiological: PEG decreased NF200 degradation (Western blot protein analysis 24 h PI) and reduced neuronal apoptosis (TUNEL staining) at injury site. Counts of retrograde labeled brainstem neurons was greater in PEG treated animals versus SLR controls (55.9 ± 8.76 vs. 33.8 ± 6.42, respectively; p < 0.05), particularly within the reticular formation. Spared tissue at the lesion epicenter and 700 mm rostral and caudal to it was greater in the PEG treated animals. Behavioral: PEG improved locomotor recovery on open field testing, with BBB scores of 7.2 ± 0.56 versus 4.5 ± 0.86 for SLR controls (p = 0.006). No significant difference was observed with inclined plane testing. |
| KwonJ Neurotrauma2009 |
Model: Female SD rats, 200–225g Injury: T10 Infinite Horizon Impactor,150 kdynes |
PEG IV • 1 g/kg@15min & 6h PI MgSO4 IV • 60 mg/kg@15min & 6h PI |
SCI + • PEG (n = 10) • MgSO4 (n = 10) • MgSO4 in PEG (n = 10) • Saline (n = 10) Sham (n = 10) |
Histologic/Biochemical/Physiological: PEG alone did not significantly reduce lesion volume at the site of injury when compared to saline controls, 6 weeks post-injury. The combination of MgSO4 in PEG resulted in a significant decrease in lesion volume. Behavioral: PEG alone did not significantly improve open field locomotion as compared to saline controls, 6 weeks post-injury. The combination of MgSO4 in PEG resulted in a significant improvement in BBB scores. |
| Ditor J Neurosci Res2007 |
Model: Male Wistar Rats, 200-250g Injury: T4 Extradural Clip Compression50g × 1 min |
PEG IV • 1 g/kg @ 15 min & 6h PI MgSO4 IV • 300 mg/kg @ 15 min & 6h PI |
SCI + • PEG (n = 11) • MgSO4 (n = 5) • MgSO4 in PEG (n = 6) • Vehicle (n = 10) |
Histologic/Biochemical/Physiological: PEG alone did not significantly reduce lesion volume. Only the combination of MgSO4 in PEG was able to significantly reduce lesion volume. Dorsal compact myelin sparring, assessed by staining with solochrome cyanin, was improved by PEG/MgSO4 and MgSO4, but not PEG alone. Behavioral: At 42d post-injury BBB scores for PEG, MgSO4, PEG/MgSO4 and vehicle were 7.3 ± 0.2, 7.7 ± 0.4, 7.6 ± 0.2 and 6.4 ± 0.6, respectively. Mechanical allodynia was significantly reduced by all interventions in comparison to vehicle controls. None of the interventions attenuated the increase of mean arterial pressure triggered by colonic distention (a measure of autonomic dysreflexia). |
| Laverty J Neurotruama2004 |
Model: Clinical Dogs, ≤40 lbs; 2–8 years old Injury: T3–L3 paraplegia resulting from acute intervertebral disk herniation |
PEG IV • 2 ml/kg of 3,500 Da, 30% w/w in sterile water Poloxamer 188 (P188) IV • 2 ml/kg of 150 mg/mL (given at the time of Xray exam, then 4-6h later) Methylprednisolone IV • 30 mg/kg Dogs included if within 72 hours of paraplegia |
SCI + • PEG + MP (n = 19) • P188 + MP (n = 16) |
Histologic/Biochemical/Physiological: SSEPs for PEG or P188-treated dogs demonstrated 63% improvement in recovered nerve conduction versus 0% in 36 historical control dogs who suffered paraplegia from acute intervertebral disk herniations. Behavioral: The occurance for a return of deep pain in hindlimbs and digits (indication of neurological recovery in complete paraplegia canine cases) was significantly greater for PEG and P188 treated dogs than historical controls. |
| Borgens J Neurosci Res2001 |
Model: Guinea Pigs < 300g Injury: Midthoracic spinal cord Crush (dura removed) with blunted forceps possessing a détente |
FITC decorated PEG (FL-PEG); in sterile lactated ringers (SLR) applied to the exposed cord • 1 cc of 50% w/w @ 0h PI FL-PEG in SLR, SQ, IP or jugular vein IV • 1 cc of 30% w/w @ 0h PI FL-PEG in SLR SQ • 1 cc of 30% w/w @ 6h PI(for functional study) |
SCI + • FL-PEG local (n = 2) • PEG in SLR SQ (n = 3) • PEG in SLR IP (n = 1) • PEG in SLR IV (n = 2) • PEG in SLR, 6h PI (n = 10) • Vehicle (n = 10) |
Histologic/Biochemical/Physiological: FL-PEG is distributed to the injured spinal cord following topical, subcutaneous, intraperitoneal and intravenous delivery. Behavioral: Subcuteaneous PEG treatment restores SSEP and CTM reflex post-injury even with a single 6 hr PI injection. |
SCI: spinal cord injury; d: day, days; h: hour, hours; w: week, weeks; PI: post-injury; q8h: interval 8 hours;
T8: thoracic vertebra 8; C5: cervical vertebra 5; IV: intravenous;
BBB: Basso, Beattie and Bresnahan locomotor test; CTM: cutaneus trunci muscle; FITC: fluorescein isothiocyanate; MDA: malondialdehyde; MP(SS): Methylprednisolone (Sodium Succinate); PEG – polyethylene Glycol; SD rats: Sprague-Dawley rat; SSEP: somatosensory evoked potentials.