Article thumbnail

Pregabalin as a Neuroprotector after Spinal Cord Injury in Rats: Biochemical Analysis and Effect on Glial Cells

By Kee-Yong Ha, Eugene Carragee, Ivan Cheng, Soon-Eok Kwon and Young-Hoon Kim

Abstract

As one of trials on neuroprotection after spinal cord injury, we used pregabalin. After spinal cord injury (SCI) in rats using contusion model, we observed the effect of pregabalin compared to that of the control and the methylprednisolone treated rats. We observed locomotor improvement of paralyzed hindlimb and body weight changes for clinical evaluation and caspase-3, bcl-2, and p38 MAPK expressions using western blotting. On histopathological analysis, we also evaluated reactive proliferation of glial cells. We were able to observe pregabalin's effectiveness as a neuroprotector after SCI in terms of the clinical indicators and the laboratory findings. The caspase-3 and phosphorylated p38 MAPK expressions of the pregabalin group were lower than those of the control group (statistically significant with caspase-3). Bcl-2 showed no significant difference between the control group and the treated groups. On the histopathological analysis, pregabalin treatment demonstrated less proliferation of the microglia and astrocytes. With this animal study, we were able to demonstrate reproducible results of pregabalin's neuroprotection effect. Diminished production of caspase-3 and phosphorylated p38 MAPK and as well as decreased proliferation of astrocytes were seen with the administration of pregabalin. This influence on spinal cord injury might be a possible approach for achieving neuroprotection following central nervous system trauma including spinal cord injury

Topics: Original Article
Publisher: The Korean Academy of Medical Sciences
OAI identifier: oai:pubmedcentral.nih.gov:3051089
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2001). Acute spinal cord injury, Part I: pathophysiologic mechanisms. Clin Neuropharmacol
  2. (2001). Apoptotic and anti-apoptotic mechanisms following spinal cord injury.
  3. (2000). Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia
  4. (2010). Astrocytes in the damaged brain: molecular and cellular insights into their reactive response and healing potential. Biochem Pharmacol
  5. (2007). Astrocytes--friends or foes in multiple sclerosis? Glia
  6. (2006). Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury.
  7. (2003). Continuous intrathecal infusion of SB203580, a selective inhibitor of p38 mitogen-activated protein kinase, reduces the damage of hind-limb function after thoracic spinal cord injury in rat. Neurosci Res
  8. (2008). Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus
  9. (2005). Current status of clinical trials for acute spinal cord injury. Injury
  10. (2008). Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury. J Pharmacol Exp Ther
  11. (1995). Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia.
  12. (2005). Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine estrogens via down-regulation of caspase-3 and prevention of mitochondrial cytochrome c release.
  13. (2008). Glutamate-induced losses of oligodendrocytes and neurons and activation of caspase-3 in the rat spinal cord. Neuroscience
  14. (1999). Induction of apoptosis signal regulating kinase 1 (ASK1) after spinal cord injury in rats: possible involvement of ASK1-JNK and -p38 pathways in neuronal apoptosis.
  15. (2008). Molecular mechanisms of Fas-mediated cell death in oligodendrocytes.
  16. (1976). Neuroprotective effects of caspase-3 inhibition on functional recovery and tissue sparing after acute spinal cord injury. Spine (Phila Pa
  17. (2005). NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature
  18. (2007). p38alpha MAP kinase mediates hypoxia-induced motor neuron cell death: a potential target of minocycline’s neuroprotective action. Neurochem Res
  19. (2004). Pathophysiology and pharmacologic treatment of acute spinal cord injury.
  20. (2006). Pregabalin action at a model synapse: binding to presynaptic calcium channel alpha2-delta subunit reduces neurotransmission in mice.
  21. (2003). Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain
  22. (2008). Pregabalin as a neuroprotector after spinal cord injury in rats.
  23. (2007). Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats. Gut
  24. (2007). Pregabalin: a novel gammaaminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clin Ther
  25. (2004). Reactive astrocytes protect tissue and preserve function after spinal cord injury.
  26. (2004). Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation.
  27. (1985). Spinal cord contusion in the rat; behavioral analysis of functional neurologic impairment. Exp Neurol
  28. (2004). The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration.
  29. (2005). The role of inducible nitric oxide synthase following spinal cord injury in rat.