Ventrolateral lesions at the ponto-medullary junction and the effects of noradrenaline on respiratory rhythm in rat brainstem-spinal cord preparations
ABSTRACT We examined whether responses of respiratory frequency (fR) to noradrenaline (NA) were eliminated by mechanical lesions in the ventrolateral area at the ponto-medullary junction in preparations of newborn rat pons-medulla-spinal cord (PMS).
Preparations obtained from 2- to 4-day-old rats were superfused with artificial cerebrospinal fluid that was equilibrated with oxygenated (95% O2 plus 5% CO2 gas, and fR was monitored at the C4 ventral root at 24 degrees C. Bilateral lesions were made in the ventrolateral area between the VIth cranial nerve root and the anterior inferior cerebellar artery in PMS (n=11). The resting fR and response to exogenous NA (7 microM) were compared with those of medulla-spinal cord (MS) preparations (n=6). Immunohistochemistry of PMS preparations was performed to detect tyrosine hydroxylase (TH)-positive neurons at the ponto-medullary junction.
PMS preparations with the lesions had (1) a significantly higher resting fR but 2 significantly less fR facilitation after NA application than those of intact PMS preparations, and (3) significantly lower resting fR and (4) significantly less fR reduction after NA application than those of MS preparations. TH-positive neurons were detected in the region from the rostral dorsolateral to the caudal ventrolateral pons (the A5 area), as well as in the ventral area near the facial nucleus.
Results suggest that ventrolateral area at ponto-medullary junction plays a significant role in exogenous NA-induced fR changes under the influence of pons-induced tonic fR inhibition in newborn rat brainstem-spinal cord preparations.
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ABSTRACT: Orexins (hypocretins) play a crucial role in arousal, feeding, and endocrine function. We previously reported that orexin-B activated respiratory neurons in the isolated brainstem-spinal cords of neonatal rats. We herein determined whether orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil. We recorded C4 nerve bursts as an index of inspiratory activity in a brainstem-spinal cord preparation. The preparation was superfused with a solution equilibrated with 3% sevoflurane alone for 10 min and the superfusate was then switched to a solution containing sevoflurane plus orexin-B. Sevoflurane decreased the C4 burst rate and the integrated C4 amplitude. The C4 burst rate and amplitude were reversed by 0.5 μM orexin-B, but not by 0.1 μM orexin-B. The decrease induced in the C4 burst rate by 10 μM propofol or 0.01 μM remifentanil was significantly antagonized by 0.1 μM orexin-B. Respiratory depression induced by a higher concentration (0.1 μM) of remifentanil was not restored by 0.1 μM orexin-B. These results demonstrated that orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil.Respiratory Physiology & Neurobiology 10/2014; 205. DOI:10.1016/j.resp.2014.10.013 · 1.97 Impact Factor