dizocilpine-maleate and Paraplegia

Catheterization of the subarachnoid space provides a convenient means to deliver drugs to, or collect cerebrospinal fluid from, the spinal cord in animal experiments, and has been instrumental to our understanding of spinal mechanisms that underlie anesthesia, analgesia, or cardiovascular regulation. Experience gained over the years has revealed several shortcomings of this technique. We report a procedure that encompasses the benefits of direct subarachnoid catheterization of the rat thoracic spinal cord but circumvents the known shortcomings. An intrathecal catheter was fabricated with a small silicon bead at one end of a PE-10 catheter, which was cannulated with a 4/0 suture that served as a guide. Using the L-shape hook of the suture guide as an anchorage, the catheter was advanced into the subarachnoid space until the silicon bead was lodged on a drilled hole (2 x 2 mm) over the lamina proper on the T13 vertebrae. With less surgical trauma, greater precision of placement and firmer anchorage of the catheter, less leakage of cerebrospinal fluid, and minimal mortality or morbidity, our modified procedure for catheterization of the thoracic spinal subarachnoid space in the rat compared favorably to previously reported methods.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Anesthesia, Spinal; Animals; Catheterization; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Male; Muscle, Smooth, Vascular; Paraplegia; Pentobarbital; Radiography; Rats; Rats, Sprague-Dawley; Subarachnoid Space; Thoracic Vertebrae

Experimental laboratory investigation of the effects of serotonergic and glutamatergic drugs in early paraplegic mice.. To examine whether NMDA and 5-HT receptors synergistically participate to generate basic stepping movements in paraplegic mice.. Laval University Medical Center, Quebec, Canada.. Adult mice completely spinalized at the low-thoracic level 1 week earlier were suspended in harnesses for experiments. Acute drug-induced effects were examined on hindlimb movements filmed with a digital video camera. Detailed kinematic analyses included stick diagrams reconstructions of hindlimb movements and analysis of bilateral coordination, angular excursion, stepping amplitude and frequency.. A single treatment with the 5-HT2 agonist quipazine (>0.7 mg/kg, i.p.) induced episodes of air-stepping movements in the hindlimbs of paraplegic mice. In contrast, injection of the glutamatergic agonist NMDA (1-45 mg/kg i.p.) failed to induce rhythmicity, although nonlocomotor rhythmic movements were observed with higher doses (45-60 mg/kg i.p.). Subthreshold doses of NMDA (22-30 mg/kg) could induce episodes of hindlimb air-stepping if combined with subthreshold doses of quipazine (0.3-0.7 mg/kg). Air-stepping was entirely blocked by administration of the selective NMDA antagonist MK-801.. A single treatment with quipazine can trigger episodes of locomotor-like movements in early chronic spinal mice. Even though NMDA alone could not generate bilaterally coordinated air-stepping, NMDA receptor activation was nonetheless critical for spinal locomotor rhythmogenesis induced by 5-HT agonists in awake behaving animals.

Topics: Animals; Dizocilpine Maleate; Drug Synergism; Excitatory Amino Acid Antagonists; Male; Mice; Motor Activity; N-Methylaspartate; Paraplegia; Quipazine; Receptors, N-Methyl-D-Aspartate; Serotonin Receptor Agonists; Signal Transduction; Spinal Cord Injuries; Thoracic Vertebrae

Much evidence has been gathered to show that neurotoxicity of excitatory amino acids is mainly activated through an N-methyl-D-aspartate (NMDA) receptor cascade. We evaluated the protective effects of NMDA receptor antagonists, MK-801 and CGS19755 on spinal cord neurons using the NMDA receptor mediated neurotoxicity model in vivo.. New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate (50 mM) infusion for 10 minutes. Group B animals (n = 6) were pretreated with MK-801 (6mg/kg), a noncompetitive NMDA receptor antagonist, that was administrated intravenously for 3 hours beginning 1 hour before the segmental infusion of aspartate (50 mM) of 10 minutes. Group C animals (n = 6) received pretreatment with CGS19755 (30mg/kg), a competitive NMDA receptor antagonist, that was administrated in the same fashion as group B, followed by the segmental infusion of aspartate (50 mM). Neurologic status was scored at 12, 24, and 48 hours after operation using the Tarlov score. All the animals were sacrificed for histologic assessment at 48 hours.. Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals showed significantly better neurologic function compared with group A (p = 0.0013, A vs. B) (p = 0.0011, A vs. C). Pathohistological change was not observed in group B and C animals.. NMDA receptor antagonists can have protective effects on spinal cord neurons against aspartate induced neurotoxicity. This model may be useful in assaying protective agents in the spinal cord against neuronal injury mediated by NMDA receptors in vivo.

Topics: Animals; Aspartic Acid; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Male; Neurons; Neuroprotective Agents; Paraplegia; Pipecolic Acids; Rabbits; Spinal Cord

Considerable evidence exists that neurotoxicity of excitatory amino acids is related to the neuronal injury, including paraplegia. However, little is known about aspartate neurotoxicity in the spinal cord in vivo. We evaluated the detrimental effects of exogenous aspartate on spinal cord neurons under metabolic stress.. New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate 50 mmol/L) infusion for 10 minutes. Group B animals (n = 7) received saline as a negative control. Group C animals (n = 5) received segmental aspartate 100 mmol/L) infusion for 5 minutes. Group D animals (n = 7) were pretreated with segmental infusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (MK-801) (6 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist for 1 minute, followed by segmental infusion of aspartate (50 mmol/L) for 9 minutes. Group E animals (n = 7) received vehicle only, followed by aspartate (50 mmol/L) infusion as a control of group D. Neurologic status was assessed at 12, 24, and 48 hours after operation using the Tarlov score.. Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals recovered fully. Group D animals showed significantly better neurologic function (p = 0.0007) compared with group E animals that exhibited paraplegia or paraparesis.. Exogenous aspartate can have detrimental effects on spinal cord neurons under metabolic stress. This model may be useful in assaying neuronal injury mediated by NMDA receptor in vivo.

Topics: Animals; Aspartic Acid; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Male; Models, Animal; Neurons; Paraplegia; Rabbits; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Stress, Physiological