Adenosine A2a receptors modulate TrkB receptor-dependent respiratory plasticity in neonatal rats.

Neuroplasticity is a fundamental property of the respiratory control system, enabling critical adaptations in breathing to meet the challenges, but little is known whether neonates express neuroplasticity similar to adults. We tested the hypothesis that, similar to adults, tyrosine receptor kinase B (TrkB) or adenosine A2a receptor activation in neonates are independently sufficient to elicit respiratory motor facilitation, and that co-induction of TrkB and A2a receptor-dependent plasticity undermines respiratory motor facilitation. TrkB receptor activation with 7,8-dihydroxyflavone (DHF) in neonatal brainstem-spinal cord preparations induced a long-lasting increase in respiratory motor output in 55 % of preparations, whereas adenosine A2a receptor activation with CGS21680 only sporadically induced respiratory motor plasticity. CGS21680 and DHF co-application prevented DHF-dependent respiratory motor facilitation, whereas co-application of MSX-3 (adenosine A2a receptor antagonist) and DHF more rapidly induced respiratory motor plasticity. Collectively, these data suggest that mechanisms underlying respiratory neuroplasticity may be only partially operational in early neonatal life, and that adenosine A2a receptor activation undermines TrkB-induced respiratory plasticity.

One bout of neonatal inflammation impairs adult respiratory motor plasticity in male and female rats.

Neonatal inflammation is common and has lasting consequences for adult health. We investigated the lasting effects of a single bout of neonatal inflammation on adult respiratory control in the form of respiratory motor plasticity induced by acute intermittent hypoxia, which likely compensates and stabilizes breathing during injury or disease and has significant therapeutic potential. Lipopolysaccharide-induced inflammation at postnatal day four induced lasting impairments in two distinct pathways to adult respiratory plasticity in male and female rats. Despite a lack of adult pro-inflammatory gene expression or alterations in glial morphology, one mechanistic pathway to plasticity was restored by acute, adult anti-inflammatory treatment, suggesting ongoing inflammatory signaling after neonatal inflammation. An alternative pathway to plasticity was not restored by anti-inflammatory treatment, but was evoked by exogenous adenosine receptor agonism, suggesting upstream impairment, likely astrocytic-dependent. Thus, the respiratory control network is vulnerable to early-life inflammation, limiting respiratory compensation to adult disease or injury.

Comparative analgesic efficacy of morphine sulfate and butorphanol tartrate in koi (Cyprinus carpio) undergoing unilateral gonadectomy.

OBJECTIVE: To identify pain-related behaviors and assess the effects of butorphanol tartrate and morphine sulfate in koi (Cyprinus carpio) undergoing unilateral gonadectomy. Design-Prospective study. ANIMALS: 90 adult male and female koi. PROCEDURES: Each fish received saline (0.9% NaCl) solution (which is physiologically compatible with fish) IM, butorphanol (10 mg/kg [4.5 mg/lb], IM), or morphine (5 mg/kg [2.3 mg/lb], IM) as an injection only (6 fish/treatment); an injection with anesthesia and surgery (12 fish/treatment); or an injection with anesthesia but without surgery (12 fish/treatment). Physiologic and behavioral data were recorded 12 hours before and at intervals after treatment. RESULTS: Compared with baseline values, the saline solution-surgery group had significantly decreased respiratory rates (at 12 to 24 hours), food consumption assessed as a percentage of floating pellets consumed (at 0 to 36 hours), and activity score (at 0 to 48 hours). Respiratory rate decreased in all butorphanol-treated fish; significant decreases were detected at fewer time points following morphine administration. In the butorphanol-surgery group, the value for food consumption initially decreased but returned to baseline values within 3 hours after treatment; food consumption did not change in the morphine-surgery group. Surgery resulted in decreased activity, regardless of treatment, with the most pronounced effect in the saline solution-surgery group. Changes in location in water column, interactive behavior, and hiding behavior were not significantly different among groups. Butorphanol and morphine administration was associated with temporary buoyancy problems and temporary bouts of excessive activity, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol and morphine appeared to have an analgesic effect in koi, but morphine administration caused fewer deleterious adverse effects. Food consumption appeared to be a reliable indicator of pain in koi.

Brain slice on a chip: opportunities and challenges of applying microfluidic technology to intact tissues.

Isolated brain tissue, especially brain slices, are valuable experimental tools for studying neuronal function at the network, cellular, synaptic, and single channel levels. Neuroscientists have refined the methods for preserving brain slice viability and function and converged on principles that strongly resemble the approach taken by engineers in developing microfluidic devices. With respect to brain slices, microfluidic technology may 1) overcome the traditional limitations of conventional interface and submerged slice chambers and improve oxygen/nutrient penetration into slices, 2) provide better spatiotemporal control over solution flow/drug delivery to specific slice regions, and 3) permit successful integration with modern optical and electrophysiological techniques. In this review, we highlight the unique advantages of microfluidic devices for in vitro brain slice research, describe recent advances in the integration of microfluidic devices with optical and electrophysiological instrumentation, and discuss clinical applications of microfluidic technology as applied to brain slices and other non-neuronal tissues. We hope that this review will serve as an interdisciplinary guide for both neuroscientists studying brain tissue in vitro and engineers as they further develop microfluidic chamber technology for neuroscience research.

Spinal cord injury-induced changes in breathing are not due to supraspinal plasticity in turtles (Pseudemys scripta).

After occurrence of spinal cord injury, it is not known whether the respiratory rhythm generator undergoes plasticity to compensate for respiratory insufficiency. To test this hypothesis, respiratory variables were measured in adult semiaquatic turtles using a pneumotachograph attached to a breathing chamber on a water-filled tank. Turtles breathed room air (2 h) before being challenged with two consecutive 2-h bouts of hypercapnia (2 and 6% CO2 or 4 and 8% CO2). Turtles were spinalized at dorsal segments D8-D10 so that only pectoral girdle movement was used for breathing. Measurements were repeated at 4 and 8 wk postinjury. For turtles breathing room air, breathing frequency, tidal volume, and ventilation were not altered by spinalization; single-breath (singlet) frequency increased sevenfold. Spinalized turtles breathing 6-8% CO2 had lower ventilation due to decreased frequency and tidal volume, episodic breathing (breaths/episode) was reduced, and singlet breathing was increased sevenfold. Respiratory variables in sham-operated turtles were unaltered by surgery. Isolated brain stems from control, spinalized, and sham turtles produced similar respiratory motor output and responded the same to increased bath pH. Thus spinalized turtles compensated for pelvic girdle loss while breathing room air but were unable to compensate during hypercapnic challenges. Because isolated brain stems from control and spinalized turtles had similar respiratory motor output and chemosensitivity, breathing changes in spinalized turtles in vivo were probably not due to plasticity within the respiratory rhythm generator. Instead, caudal spinal cord damage probably disrupts spinobulbar pathways that are necessary for normal breathing.