Alterations in excitatory and inhibitory brainstem interneuronal circuits after severe spinal cord injury

J Neurotrauma. 2010 Apr;27(4):721-8. doi: 10.1089/neu.2009.1089.

Abstract

Reorganization of the central nervous system following spinal cord injury (SCI) involves changes not only at the cortical level, but also at the level of the brainstem. To further understand changes in excitatory and inhibitory brainstem interneuronal circuits following SCI, we studied recovery curves of the blink reflex (BR) to paired suprathreshold stimuli at various intervals (160, 300, 500, and 1000 msec), and prepulse inhibition of the BR following right index finger stimulation 100 msec prior to supraorbital nerve stimulation. Both parameters were studied in patients with SCI without baclofen treatment (n = 19), in patients with continuous intrathecal baclofen (CITB) (n = 9), and in healthy controls (n = 13). R2 recovery, expressed as the ratio of R2 area following the second stimulus divided by the R2 area following the first stimulus, was significantly greater in SCI patients without baclofen compared to controls and patients with CITB at all intervals, while there was no difference between patients with CITB and controls. Prepulse inhibition of R2 was significantly less in patients without baclofen compared to patients with CITB and healthy controls. Our findings indicate enhanced excitability and reduced inhibition of brainstem interneuronal circuits in patients with SCI, that are restored in the presence of baclofen to levels comparable to controls. In conclusion, SCI patients show more extended alterations in brainstem circuitry than previously thought. Decreased GABAergic mechanisms seem to be related to both excitatory and inhibitory brainstem circuit alterations. Baclofen appears to effectively restore this decreased GABAeregic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Baclofen / pharmacology
  • Baclofen / therapeutic use
  • Blinking / drug effects
  • Blinking / physiology
  • Brain Stem / drug effects
  • Brain Stem / metabolism
  • Brain Stem / physiopathology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Female
  • GABA Agonists / pharmacology
  • GABA Agonists / therapeutic use
  • Humans
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Male
  • Middle Aged
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology*
  • Neuronal Plasticity / physiology
  • Physical Stimulation
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Sensory Gating / drug effects
  • Sensory Gating / physiology
  • Spinal Cord Injuries / physiopathology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Young Adult
  • gamma-Aminobutyric Acid / deficiency*

Substances

  • GABA Agonists
  • gamma-Aminobutyric Acid
  • Baclofen