Preclinical evidence 4
4 studies reported at therapy level; 4 evidence entries itemised.
RatSpinal cord injuryComplete transectionWistarn = Twitch time course: 5 rats per group (vehicle, 60 mg/kg, 12…Intraperitoneal injection in vivo; bath application in vitro60 mg/kg or 120 mg/kg in vivo; 30 micromolar bath applied i…Postoperative day 4 to 5, after stable spastic motor behaviour was established
Model: Complete spinal cord transection at T8 to T9 in neonatal rats, with sham laminectomy controls
Acute calpain inhibition dose dependently reduced spasticity signs, limited Nav and KCC2 proteolysis, decreased the persistent sodium current by 16 per cent and increased oligomeric KCC2 by 21 per cent, with no effect in sham or intact animals.
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RatTBIWeight-drop / impact-accelerationSprague-Dawleymalen = Total not stated; 3 to 4 rats per group for individual assa…intracranial microinjection at lesion site, 1.0 mm depth; BMSCs engrafted into injury epicentre at 1 uL/min1.0 uL of 50 mM MDL28170 in 20 percent DMSO; BMSC dose repo…MDL28170 at 30 min post-injury; BMSCs at 24 h post-injury
Model: Weight-drop parietal contusion, 5 mm burr hole right parietal bone, 50 g hammer from 30 cm
MDL28170 preconditioning reduced pro-inflammatory cytokines and graft apoptosis, increased survival of transplanted BMSCs and reduced lesion cavity and neurological deficit compared with BMSCs alone.
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RatChemical/toxinSprague-DawleyWithin 1 h after exposure
Model: Bromine inhalation exposure with resulting acute cardiac injury; exposure concentration and duration not stated in the retrieved text. A separate experiment injected 2-bromohexadecanal into the left ventricular cavity of a normal rat
Bromine inhalation caused acute cardiac ultrastructural damage, biomarker rises and left ventricular systolic and diastolic dysfunction, and MDL28170 given within 1 h of exposure significantly decreased left ventricular calpain activity and acute mortality.
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MouseTBIControlled cortical impactBALB/cMalen = 108 mice in total; 6 per group for ultrastructure and histo…Intraperitoneal20 mg/kg, dissolved in 0.9 per cent sodium chlorideFirst dose 5 minutes after controlled cortical impact
Model: Controlled cortical impact over the right parietal cortex (3 mm tip, 2 m/s velocity, 85 ms compression time, 1 mm compression depth), described as moderate injury
MDL28170 reduced contusion volume (9.30 plus or minus 1.05 and 9.90 plus or minus 1.17 cubic mm versus 16.90 plus or minus 1.01 and 17.20 plus or minus 1.17 cubic mm), lowered brain water content and Evans blue leakage, improved neurological severity scores (7.50 plus or minus 0.45 and 6.33 plus or…
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