Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting

Aldric T. Hama, James R. Unnerstall, Julie B. Siegan, Jacqueline Sagen

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Excessive activation of N-methyl-d-aspartate (NMDA) receptors in the spinal cord consequent to peripheral injury has been implicated in the initiation of neuropathologic events leading to a state of chronic hyperexcitability and persistence of exaggerated sensory processing. In other CNS disease or injury states, NMDA-mediated neurotoxic damage is associated with a loss of NMDA receptors, and outcome may be improved by agents reducing NMDA activation. Previous findings in our laboratory have demonstrated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory abnormalities and reduce the induction of a putative nitric oxide synthase consequent to peripheral nerve injury. In order to determine changes in NMDA receptor expression in the spinal cord following peripheral nerve injury and adrenal medullary grafting, NMDA receptor binding using a high-affinity competitive NMDA receptor antagonist, CGP-39653, and NMDAR1 subunit distribution using immunocytochemistry were investigated. Two weeks following peripheral nerve injury by loose ligation of the right sciatic nerve, either adrenal medullary or striated muscle (control) tissue pieces were implanted in the spinal subarachnoid space. Binding studies revealed a marked reduction in [3H]CGP-39653 binding at L4-L5 levels ipsilateral to peripheral nerve injury in control transplanted animals. In contrast, NMDA binding was normalized in adrenal medullary grafted animals. In addition, NMDAR1 immunoreactivity was reduced in both the dorsal horn neuropil and motor neurons of the ventral horn in animals with peripheral nerve injury, while levels in adrenal medullary grafted animals appeared similar to intact controls. These results suggest that adrenal medullary transplants reduce abnormal sensory processing resulting from peripheral injury by intervening in the spinal NMDA-excitotoxicity cascade.

Original languageEnglish (US)
Pages (from-to)103-113
Number of pages11
JournalBrain Research
Volume687
Issue number1-2
DOIs
StatePublished - Jul 31 1995
Externally publishedYes

Keywords

  • CGP-39653
  • Dorsal horn
  • Excitotoxicity
  • Motor neuron
  • Neural transplant
  • NMDAR1 subunit
  • Nociception
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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