Functional magnetic resonance imaging within the rat spinal cord following peripheral nerve injury

Functional magnetic resonance imaging (fMRI) was used to detect the effects of graded peripheral nerve injury at the spinal level. Graded peripheral nerve injury in rats was accomplished by transection of nerves entering the spinal cord at the L3 and L4 levels of the spinal cord segments. Electrical stimulation of the hindpaw was used to elicit activity within the spinal cord. The stimulation experimental paradigm consisted of 62 functional images, 5 slices each, with a total of 3 rest and 2 stimulation periods. A 9.4 T MRI system and a quadrature volume rf coil covering the lumbar spinal cord were used for the fMRI study. Sets of fast spin echo images were acquired repeatedly following sham preparatory surgery under control conditions and in rats following sham surgery (pre nerve cut), followed by L3 nerve and then L4 nerve section. In rats with sham surgery, there was a significant activation within the dorsal horn of slices corresponding to L3 and L4 spinal cord segments. Following section of the L3 nerve, there was a reduction in the number of active voxels in the L3 and L4 spinal cord segments. The activation was reduced further by sectioning of the L4 nerve. Thus, following an increasing loss of axonal connections to the spinal cord, there was a decreasing number of active voxels within the spinal cord. The results demonstrate that spinal fMRI in the rat has sufficient sensitivity to detect within the spinal cord the effects of a graded reduction in peripheral connectivity.

[1]  Patrick W Stroman,et al.  Functional imaging of the rat cervical spinal cord , 2002, Journal of magnetic resonance imaging : JMRI.

[2]  S. Dohi,et al.  Effects of succinylcholine on spinal antinociception with lidocaine in rats , 2005 .

[3]  T. Gordh,et al.  Variation in rat sciatic nerve anatomy: Implications for a rat model of neuropathic pain , 2000, Journal of the peripheral nervous system : JPNS.

[4]  J E Swett,et al.  The somatotopic organization of primary afferent terminals in the superficial laminae of the dorsal horn of the rat spinal cord , 1985, The Journal of comparative neurology.

[5]  Mehmet Bilgen.  Comparison of spinal vasculature in mouse and rat: investigations using magnetic resonance angiography , 2006 .

[6]  Hiroshi Baba,et al.  Peripheral nerve injury alters excitatory synaptic transmission in lamina II of the rat dorsal horn , 2003, The Journal of physiology.

[7]  D Le Bars,et al.  Effects of heterotopic noxious stimuli on activity of neurones in subnucleus reticularis dorsalis in the rat medulla. , 1994, The Journal of physiology.

[8]  Patrick D. Wall,et al.  Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input , 1987, Nature.

[9]  S. Harris,et al.  Plantar motoneuron columns in the rat , 1987, The Journal of comparative neurology.

[10]  R. Coghill,et al.  Spatial distribution of nociceptive processing in the rat spinal cord. , 1991, Journal of neurophysiology.

[11]  Marc-Antoine Rousseau,et al.  Ventral Approach to the Lumbar Spine of the Sprague-Dawley Rat , 2004, Lab Animal.

[12]  P. Stroman,et al.  Functional MRI of motor and sensory activation in the human spinal cord. , 2001, Magnetic resonance imaging.

[13]  Xiao Ming Xu,et al.  Innervation and Properties of the Rat FDSBQ Muscle: An Animal Model to Evaluate Voluntary Muscle Strength after Incomplete Spinal Cord Injury , 1999, Experimental Neurology.

[14]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[15]  Ravi S. Menon,et al.  On the characteristics of functional magnetic resonance imaging of the brain. , 1998, Annual review of biophysics and biomolecular structure.

[16]  S. Abram,et al.  Spinal cord metabolic response to noxious radiant heat stimulation of the cat hind footpad , 1986, Brain Research.

[17]  M. Norenberg,et al.  The pathology of human spinal cord injury: defining the problems. , 2004, Journal of neurotrauma.

[18]  I-Ming Jou,et al.  The Effects From Lumbar Nerve Root Transection in Rats on Spinal Somatosensory and Motor-Evoked Potentials , 2004, Spine.

[19]  R Baumgartner,et al.  Comparison of two exploratory data analysis methods for fMRI: fuzzy clustering vs. principal component analysis. , 2000, Magnetic resonance imaging.

[20]  A. Blight,et al.  Cellular morphology of chronic spinal cord injury in the cat: Analysis of myelinated axons by line-sampling , 1983, Neuroscience.

[21]  Toshiki Endo,et al.  Blood Oxygenation Level-Dependent Visualization of Synaptic Relay Stations of Sensory Pathways along the Neuroaxis in Response to Graded Sensory Stimulation of a Limb , 2006, The Journal of Neuroscience.

[22]  E C Wong,et al.  Magnetic resonance imaging of human brain function. Principles, practicalities, and possibilities. , 1997, Neurosurgery clinics of North America.

[23]  Mathias Hoehn,et al.  Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition , 2007, NMR in biomedicine.

[24]  Patrick W. Stroman,et al.  Comparison of functional activity in the rat cervical spinal cord during alpha-chloralose and halothane anesthesia , 2007, NeuroImage.

[25]  P Sabbah,et al.  Sensorimotor cortical activity in patients with complete spinal cord injury: a functional magnetic resonance imaging study. , 2002, Journal of neurotrauma.

[26]  Patrick W. Stroman,et al.  Functional magnetic resonance imaging of the human brain and spinal cord by means of signal enhancement by extravascular protons , 2003 .

[27]  M. Yoshimura,et al.  Analysis of receptive fields revealed by in vivo patch-clamp recordings from dorsal horn neurons and in situ intracellular recordings from dorsal root ganglion neurons. , 2004, Life sciences.

[28]  J B Green,et al.  Cortical sensorimotor reorganization after spinal cord injury , 1998, Neurology.

[29]  Mehmet Bilgen,et al.  Magnetic resonance angiography of rat spinal cord at 9.4 T: A feasibility study , 2005, Magnetic resonance in medicine.

[30]  W. M. Panneton,et al.  The central termination of sensory fibers from nerves to the gastrocnemius muscle of the rat , 2005, Neuroscience.

[31]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[32]  Donald D. Price,et al.  The roles of spatial recruitment and discharge frequency in spinal cord coding of pain: a combined electrophysiological and imaging investigation , 1993, Pain.

[33]  Jeff W Lichtman,et al.  In vivo imaging of axonal degeneration and regeneration in the injured spinal cord , 2005, Nature Medicine.

[34]  Louis Sokoloff,et al.  The [ 14 C]Deoxyglucose Method for Measurement of Local Cerebral Glucose Utilization , 1989 .

[35]  B. Tomanek,et al.  Simultaneous functional magnetic resonance imaging in the rat spinal cord and brain , 2006, Experimental Neurology.

[36]  P W Stroman,et al.  Functional magnetic resonance imaging of the human cervical spinal cord with stimulation of different sensory dermatomes. , 2002, Magnetic resonance imaging.

[37]  L. Charron,et al.  Motoneuronal and motor axonal innervation in the rat hindlimb: A comparative study using horseradish peroxidase , 2004, Experimental Brain Research.

[38]  Alyson Fox,et al.  Metabotropic Glutamate Receptor 5 Upregulation in A-Fibers after Spinal Nerve Injury: 2-Methyl-6-(Phenylethynyl)-Pyridine (MPEP) Reverses the Induced Thermal Hyperalgesia , 2002, The Journal of Neuroscience.

[39]  Mehmet Bilgen,et al.  Ex vivo magnetic resonance imaging of rat spinal cord at 9.4 T. , 2005, Magnetic resonance imaging.

[40]  Thomas Unger,et al.  Pathophysiological activity in rat dorsal horn neurones in segments rostral to a chronic spinal cord injury , 2003, Brain Research.

[41]  Walker Jm,et al.  Cannabinoid WIN 55,212-2 Inhibits the Activity-Dependent Facilitation of Spinal Nociceptive Responses , 1999 .

[42]  J. Michael Walker,et al.  Cannabinoid WIN 55,212-2 inhibits the activity-dependent facilitation of spinal nociceptive responses. , 1999, Journal of neurophysiology.

[43]  Patrick W Stroman,et al.  Correlation of functional activation in the rat spinal cord with neuronal activation detected by immunohistochemistry , 2004, NeuroImage.

[44]  S. R. Browd,et al.  Functional MRI of Motor and Sensory Cortex as a Potential Presurgical Mapping Modality and Technique for Longitudinal Studies of Neuroplasticity: A Case Study. , 1998, NeuroImage.

[45]  Ravi S. Menon,et al.  Imaging function in the working brain with fMRI , 2001, Current Opinion in Neurobiology.

[46]  Rudolf Hebel,et al.  Anatomy of the Laboratory Rat , 1976 .

[47]  Sergio Tufik,et al.  Afferent pain pathways: a neuroanatomical review , 2004, Brain Research.

[48]  P. W. Stroman,et al.  Mapping of Neuronal Function in the Healthy and Injured Human Spinal Cord with Spinal fMRI , 2002, NeuroImage.