Table 3. Effect of calpain inhibitors on axonal pathology from anoxia, ischemia, complement activation, and α-latrotoxin.

Model	Inhibitor(s)	Effect of Calpain Inhibitor(s)	Reference
OGD; cortical neuronal culture	MDL-28170 Calpastatin overexpression	Preserves βIV-spectrin labeled AIS 24 h post-OGD. IC50 for MDL-28170 = ~10 μM.	Schafer et al., 2009
MCAO (90 min) in vivo	MDL-28170 IV bolus and infusion (total dose 40 mg/kg)	Preserves βIV-spectrin and Nav labeled AIS in infarcted cortex 24 h post-MCAO.	Schafer et al., 2009
Anoxia± reoxygenation; optic nerves ex vivo	MDL-28170 (50-100 μM) ALLN (30-100 μM)	Reduces αII-spectrin proteolysis (western blot), presumably in axons. No improvement in CAP (area under the CAP).	Jiang and Stys, 2000
Anoxia or OGD; optic nerves ex vivo	MDL-28170 (50 μM) ALLN (10 μM)	Reduces NFM and NFH proteolysis, and NFH dephosphorylation (western blot). No improvement in CAP (area under the CAP).	Stys and Jiang, 2002
OGD; extensor digitorum longus preparation from mice that express YFP in motor neurons	Calpain inhibitor VI (100 μM)	Reduces NMJ denervation (loss of YFP fluorescence) 120 min post-OGD.	Talbot et al., 2012
Anti-GD1a antibody with complement; intramuscular axons in ex vivo triangularis sterni muscle	AK295 (100 μM)	Preserves immunostaining for Nav1.6, ankG, and Caspr at nodes and paranodes, and immunostaining for NF at NMJs. No improvement in perineural currents at nodes or terminals.	McGonigal et al., 2010
Anti-GD1a antibody with complement; desheathed phrenic nerves ex vivo	AK295 (100 μM)	Preserves immunostaining for Nav1.6 and Caspr, but not ankG, at nodes and paranodes. No improvement in CAP amplitude.	McGonigal et al., 2010
α-latrotoxin; NMJs in hemidiaphragm preparations	Calpeptin (50 μg/ml or 138 μM)	Preserves NFH immunostaining and “cytoskeletal bundles” in NMJs. Synaptic vesicle depletion is less pronounced with calpain inhibitor.	O’Hanlon et al., 2003
Anti-GQ1b antibody with complement; NMJs in hemidiaphragm preparations	Calpeptin (50 μg/ml or 138 μM) Calpain inhibitor V (50 μg/ml or 123 μM)	Preserves NFH immunostaining and “cytoskeletal bundles” in NMJs. Does not reduce mitochondrial damage. No effect on synaptic vesicle depletion.	O’Hanlon et al., 2003

AIS, axon initial segment; ankG, ankyrin G; CAP, compound action potential; Caspr, contactin-associated protein; MCAO, middle cerebral artery occlusion; Nav, voltage-gated Na⁺ channel; NF, neurofilament; NFH, neurofilament heavy; NFM, neurofilament medium; NMJ, neuromuscular junction; OGD, oxygen glucose deprivation