Table 2. Effect of calpain inhibitors on axonal pathology in TBI and TAI models.

Model	Inhibitor(s)	Effect of Calpain Inhibitor(s)	Reference
Fluid shear stress; dissociated forebrain neurons	ALLN (3 μM)	Reduces neurite beading (phase contrast microscopy) 60-90 min post-injury.	Kilinc et al., 2009
Impact acceleration head injury	MDL-28170 (30 mg/kg) IV 30 min before injury	Reduces β-APP and RMO-14 immunostaining of axons in the corticospinal tract and medial longitudinal fasciculus at 2 h post-injury.	Buki et al., 2003
Fluid percussion injury	MDL-28170 IV (various dosing strategies)	Inhibitor effect varies depending on dosing strategy and post-injury survival duration. Inhibitor reduces β-APP immunostaining in the corpus callosum. Although its effect on CAP is less consistent, inhibitor partially normalizes CAP amplitude and latency of first and second major peaks (corresponding to myelinated and unmyelinated axons, respectively). Amplitude correlates with number of axons generating action potentials, while latency represents velocity of action potential propagation.	Ai et al., 2007
Controlled cortical impact	ALLM IA bolus and infusion (total dose ~2.7 μmoles)	Reduces axonal swellings, bulbs, and “breaks” in white matter tracts (NFL immunostaining) 24 h post-injury.	Posmantur et al., 1997
Optic nerve stretch in vivo	MDL-28170 IV bolus and infusion (total dose 67.5 mg/kg)	No improvement in retrograde transport of Fluoro-gold 4 days post-injury.	Ma et al., 2012a
Optic nerve stretch in vivo	Calpastatin overexpression	Improves retrograde transport of Fluoro- gold 4 days post-injury.	Ma et al., 2012b
Impact acceleration head injury	MDL-28170 (30 mg/kg) IV 30 min before injury	Reduces the length, but not the thickness, of HRP-labeling of axons in the corticospinal tract 2 h post-injury. No effect observed in the medial longitudinal fasciculus.	Czeiter et al., 2009

β-APP, β-amyloid precursor protein; CAP, compound action potential; HRP, horseradish peroxidase; NFL, neurofilament light; IA, intra-arterial; IV, intravenous