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Respiratory Abnormalities Resulting from Midcervical Spinal Cord Injury and their Reversal by Serotonin 1A Agonists in Conscious Rats
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| Zeitschriftentitel: | The Journal of Neuroscience |
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| Personen und Körperschaften: | , , , , , , , , , , |
| In: | The Journal of Neuroscience, 25, 2005, 18, S. 4550-4559 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>Respiratory dysfunction after cervical spinal cord injury (SCI) has not been examined experimentally using conscious animals, although clinical SCI most frequently occurs in midcervical segments. Here, we report a C5 hemicontusion SCI model in rats with abnormalities that emulate human post-SCI pathophysiology, including spontaneous recovery processes. Post-C5 SCI rats demonstrated deficits in minute ventilation (Ve) responses to a 7% CO<jats:sub>2</jats:sub>challenge that correlated significantly with lesion severities (no injury or 12.5, 25, or 50 mm × 10 g weight drop; New York University impactor;<jats:italic>p</jats:italic>< 0.001) and ipsilateral motor neuron loss (<jats:italic>p</jats:italic>= 0.016). Importantly, C5 SCI resulted in at least 4 weeks of respiratory abnormalities that ultimately recovered afterward. Because serotonin is involved in respiration-related neuroplasticity, we investigated the impact of activating 5-HT<jats:sub>1A</jats:sub>receptors on post-C5 SCI respiratory dysfunction. Treatment with the 5-HT<jats:sub>1A</jats:sub>agonist 8-hydroxy-2-(di-<jats:italic>n</jats:italic>-propylmino)tetralin (8-OH DPAT) (250 μg/kg, i.p.) restored hypercapnic Ve at 2 and 4 weeks after injury (i.e., ∼39.2% increase vs post-SCI baseline;<jats:italic>p</jats:italic>≤ 0.033). Improvements in hypercapnic Ve response after single administration of 8-OH DPAT were dose dependent and lasted for ∼4 h(<jats:italic>p</jats:italic>≤ 0.038 and<jats:italic>p</jats:italic>≤ 0.024, respectively). Treatment with another 5-HT<jats:sub>1A</jats:sub>receptor agonist, buspirone (1.5 mg/kg, i.p.), replicated the results, whereas pretreatment with a 5-HT<jats:sub>1A</jats:sub>-specific antagonist, 4-iodo-<jats:italic>N</jats:italic>-[2-[4(methoxyphenyl)-1-piperazinyl]ethyl]-<jats:italic>N</jats:italic>-2-pyridinyl-benzamide (3 mg/kg, i.p.) given 20 min before 8-OH DPAT negated the effect of 8-OH DPAT. These results imply a potential clinical use of 5-HT<jats:sub>1A</jats:sub>agonists for post-SCI respiratory disorders.</jats:p> |
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| Umfang: | 4550-4559 |
| ISSN: |
0270-6474
1529-2401 |
| DOI: | 10.1523/jneurosci.5135-04.2005 |