Effect of Tubastatin A on the Functional Recovery of Cauda Equina Injury in Rats

World Neurosurg. 2018 Jun:114:e35-e41. doi: 10.1016/j.wneu.2018.01.190. Epub 2018 Feb 3.

Abstract

Objective: To explore the effect of the inhibitor of histone deacetylase (6HDAC6), tubastatin A, on the functional recovery of injured central branch of dorsal root ganglia (cauda equina).

Methods: A total of 30 Sprague-Dawley rats (n = 10 for each group) were divided randomly into sham operation (sham group), cauda equina compression control (CEC control group), and cauda equina compression plus tubastatin A treatment (tubastatin A group). The tail-flick test was performed to detect the sense of pain and warmth as well as motor function. Immunoblotting/immunofluorescence experiments, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and hematoxylin-eosin staining were performed to detect the amount of HDAC6 in dorsal root ganglion (DRG) neurons, degree of apoptosis in DRG neurons, and degree of cauda equina injury, respectively.

Results: The ratio of apoptotic cells in the CEC control group was greater than that in the sham group, whereas it decreased in the tubastatin A group. Hematoxylin-eosin staining revealed that the fibers of cauda equina in the tubastatin A group were more compact compared with those in the CEC control group. The expression of HDAC6 was not different between the sham and CEC control groups, whereas it decreased significantly in the tubastatin A group. Tubastatin A administration shortened tail-flick latency on the seventh day after operation compared with the CEC control group.

Conclusions: Tubastatin A significantly decreased the expression of HDAC6 in DRG neurons with injured cauda equina, inhibited the apoptosis of neural cells and axonal demyelinating changes in cauda equina, and partially promoted the recovery of neural function.

Keywords: Cauda equina injury; Deacetylation; Dorsal root ganglion; HDAC6; Tubulin post-translational modification.

MeSH terms

  • Animals
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / injuries
  • Ganglia, Spinal / physiopathology
  • Histone Deacetylase 6 / metabolism
  • Hydroxamic Acids / pharmacology*
  • Indoles / pharmacology*
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / physiopathology
  • Male
  • Neurons / drug effects
  • Peripheral Nerve Injuries / drug therapy
  • Peripheral Nerve Injuries / physiopathology
  • Radiculopathy / drug therapy
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Spinal Stenosis / drug therapy*
  • Spinal Stenosis / physiopathology

Substances

  • Hydroxamic Acids
  • Indoles
  • tubastatin A
  • HDAC6 protein, rat
  • Histone Deacetylase 6