Enolase inhibition is a potential therapeutic strategy currently being investigated for treatment of
spinal cord injury (SCI) as it reduces pro-inflammatory
cytokines and
chemokines, alters metabolic factors, and reduces
gliosis in acute SCI. Herein, the role of
enolase in SCI has been examined to better understand the effects of this
enzyme on
inflammation, metabolic
hormones, glial cell activation, and neuroprotection under these shorter injury conditions. Immunohistochemical analyses of inflammatory markers
vimentin, Cox-2, and caspase-1 indicated that
enolase inhibition attenuated the elevated levels of
inflammation seen following SCI. Iba1, GFAP, NFP, and CSPG staining indicated that
enolase inhibition with prolonged administration of
ENOblock reduced microglia/astrocyte activation and lead to enhanced neuroprotection in SCI. An analysis of metabolic
hormones revealed that
ENOblock treatment significantly upregulated plasma concentrations of
peptide YY,
glucagon-like peptide 1,
glucose-dependent insulinotropic peptide,
glucagon, and
insulin hormones as compared to vehicle-treated controls (Mann-Whitney, p ≤ 0.05).
ENOblock did not have a significant effect on plasma concentrations of
pancreatic polypeptide. Interestingly,
ENOblock treatment inhibited
chondroitin sulfate proteoglycan (CSPG), which is produced by activated glia and serves to block regrowth of axons across the lesion site following injury. An increased level of NeuN and MBP with reduced caspase-1 was detected in SCI tissues after
ENOblock treatment, suggesting preservation of myelin and induction of neuroprotection.
ENOblock also induced improved motor function in SCI rats, indicating a role for
enolase in modulating inflammatory and metabolic factors in SCI with important implications for clinical consideration.