Paraplegic Mice Research Articles

Role of NMDA receptor activation in serotonin agonist-induced air-stepping in paraplegic mice.

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.

Two Serologic Markers to Monitor the Engraftment, Growth, and Treatment Response of Human Leukemias in Severe Combined Immunodeficient Mice

We have investigated human lactate dehydrogenase (LDH) isoenzymes and human nuclear matrix protein 41/7 (NMP 41/7) as potential serologic markers to monitor the course of human leukemia in severe combined immunodeficient (SCID) mice. Following the transplantation of 10(6) human acute lymphoblastic leukemia (ALL) Nalm-6 cells, human specific LDH isoenzymes were measurable in the serum of SCID mice as early as 7 days after transplantation, although serum total LDH increased in some animals as early as 5 days after transplantation. Human NMP 41/7 was measurable in all animals at day 15 after leukemia cell injection. Serum levels of total LDH, human specific LDH and NMP 41/7 increased progressively over time, reaching total LDH levels as high as 50,000 U/L at day 25 after transplantation. To determine whether the levels of LDH and NMP 41/7 in serum were a reflection of human tumor burden, we studied these serologic markers in SCID mice bearing measurable subcutaneous human neuroblastoma tumors, or compared the serum levels of these markers with the number of human leukemia CD10+ cells in the bone marrow of the SCID mice. The serum levels of total LDH, human specific LDH isoenzymes, and NMP 41/7 correlated well with tumor burden, and they drastically decreased or disappeared from serum after the human leukemia or neuroblastoma cells were selectively killed with a single intravenous (IV) injection of 1 to 3 micrograms diphtheria toxin (DT) (the cellular receptor for DT is present on human cells, but not on mouse cells). Paraplegic mice with central nervous system leukemia completely recovered after DT treatment. We conclude that measurements of serum levels of total LDH, human LDH isoenzymes, and NMP 41/7 are sensitive, quantitative, rapid, and easy to perform serologic methods useful to monitor the engraftment, progression, and treatment response of human leukemia in SCID mice.

Developmental aspects of the effects of spinal cord transection upon audiogenic seizures in mice

The contributions of somatic sensory and motor processes during audiogenic seizures were investigated in mice. Subjects were 395 DBA/2J mice which received either complete transection of the lower thoracic spinal cord or an identical sham operation without actual cordotomy. Additional control procedures were also employed to detect “side effects” of surgery. Paraplegic mice, lacking substantial input from the posterior body, were compared with control mice for seizures. Postoperative intervals of 1 h, 1 day, 4–5 days, or 12 days were used in mice of various ages. Convulsions cephalad to paralysis were studied in two experiments. In 21 day-old-mice (at the ontogenic peak of susceptibility to audiogenic seizures), paraplegic subjects had substantially reduced incidences of wild-running attacks, clonic-tonic convulsions, and fatalities induced by a 95-dB SPL noise band (Experiment 1). In contrast to 21-day-olds, younger and older paraplegic mice did not differ from their respective control mice in seizure incidence. In fact, there was a tendency for paraplegic mice to be more susceptible to audiogenic seizures at these ages (Experiment 2). The findings indicate that interruption of spinal cord pathways influenced paroxysmal activity in the brain, and this influence was related to ontogenic factors.

Excitation of afferent cardiac sympathetic nerve fibers during coronary occlusion

Excitation of afferent cardiac sympathetic nerve fibers during coronary occlusion