期刊
JOURNAL OF NEUROSCIENCE
卷 25, 期 18, 页码 4550-4559出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5135-04.2005
关键词
spinal cord injury; cervical; hemicontusion; respiration; serotonin 1A; buspirone
资金
- NINDS NIH HHS [1-R01 NS40822, R01 NS040822] Funding Source: Medline
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% CO2 challenge that correlated significantly with lesion severities (no injury or 12.5, 25, or 50 mm x 10 g weight drop; New York University impactor; p < 0.001) and ipsilateral motor neuron loss (p = 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-HT1A receptors on post-C5 SCI respiratory dysfunction. Treatment with the 5-HT1A agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH DPAT) (250 mu g/kg, i.p.) restored hypercapnic Ve at 2 and 4 weeks after injury (i.e., similar to 39.2% increase vs post-SCI baseline; p <= 0.033). Improvements in hypercapnic Ve response after single administration of 8-OH DPAT were dose dependent and lasted for similar to 4 h (p <= 0.038 and p <= 0.024, respectively). Treatment with another 5-HT1A receptor agonist, buspirone (1.5 mg/kg, i.p.), replicated the results, whereas pretreatment with a 5-HT1A-specific antagonist, 4-iodo-N-[2[4(methoxyphenyl)-1-piperazinyl]ethyl]-N-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-HT1A agonists for post-SCI respiratory disorders.
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