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Aihua Li

Publications and source records attributed to Aihua Li.

26 records · Page 2Linked to original sources
PubMed2002

Muscimol inhibition of medullary raphé neurons decreases the CO2 response and alters sleep in newborn piglets.

Medullary raphé neurons are chemosensitive in vitro (Wang et al., J. Physiol. Lond. 511 (1998)), are involved in the ventilatory response to CO(2) in vivo (Dreshaj et al., Respir. Physiol. 111 (1998); Nattie and Li, J. Appl. Physiol. 90 (2001)), and are abnormal in many Sudden Infant Death Syndrome (SIDS) victims (Panigrahy et al., J. Neuropathol. Exp. Neurol. 59 (2000)). In this study we determine whether the ventilatory response to CO(2) is altered when medullary raphé neuronal function is focally and reversibly inhibited in chronically instrumented newborn piglets. Ventilation was measured by whole body plethysmography in room air and in 5% CO(2) before and during microdialysis of muscimol, a gamma-amino butyric acid (GABA(A)) receptor agonist, into the medullary raphé. Muscimol (10 mM in the dialysate), had no effect on eupneic ventilation, but reduced significantly the CO(2) response by 17% during wakefulness. Sleep cycling was also disrupted, as characterized by a significant increase in the percentage of time spent awake and a significant decrease in the percentage of time spent in NREM sleep. Disturbances of medullary raphé function can alter central chemoreception and normal sleep architecture, which may contribute to the pathogenesis of SIDS.

Analysis of Variance↗
PubMed2002

CO2 dialysis in one chemoreceptor site, the RTN: stimulus intensity and sensitivity in the awake rat.

We stimulate single central chemoreceptor sites in the unanesthetized rat by focal microdialysis of artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO(2). Here, in the retrotrapezoid nucleus (RTN) we measured the focal stimulus intensity with a pH electrode adjacent to the dialysis probe. During 25% CO(2) dialysis, RTN pH decreased by 0.069 (0.013, SEM) pH units (N=5), 44% of the change observed during 7% CO(2) breathing, -0.157 (0.019) pH units (N=4). During 7% CO(2) breathing, Pa(CO(2)) increased by 15 Torr (N=5). We calculate the deltaPa(CO(2)) that would produce a deltapH at the RTN approximately like that observed during 25% CO(2) dialysis as 44% of 15 Torr, or 6.6 Torr deltaPa(CO(2)). Using ventilatory response data from our lab, we estimate overall chemoreceptor sensitivity as 13% deltaVE/Torr deltaPa(CO(2)) and RTN sensitivity as 3% deltaVE/Torr deltaPa(CO(2)). The RTN provides 23% of the overall response. This may be an underestimate. During RTN stimulation Pa(CO(2)) decreases by 4.9 (0.7) Torr (N=5), which may inhibit other chemoreceptor sites. Multiple chemoreceptor sites may interact to provide high sensitivity in systemic hypercapnia and stability during heterogeneous stimulation and inhibition.

Animals↗
PubMed2002

Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity.

All medullary central chemoreceptor sites contain neurokinin-1 receptor immunoreactivity (NK1R-ir). We ask if NK1R-ir neurons and processes are involved in chemoreception. At one site, the retrotrapezoid nucleus/parapyramidal region (RTN/Ppy), we injected a substance P-saporin conjugate (SP-SAP; 0.1 pmol in 100 nl) to kill NK1R-ir neurons specifically, or SAP alone as a control. We made measurements for 15 days after the injections in two groups of rats. In group 1, with unilateral injections made in the awake state via a pre-implanted guide cannula, we compared responses within rats using initial baseline data. In group 2, with bilateral injections made under anaesthesia at surgery, we compared responses between SP-SAP- and SAP-treated rats. SP-SAP treatment reduced the volume of the RTN/Ppy region that contained NK1R-ir neuronal somata and processes by 44 % (group 1) and by 47 and 40 % on each side, respectively (group 2). Ventilation (.V(E)) and tidal volume (V(T)) were decreased during air breathing in sleep and wakefulness (group 2; P < 0.001; two-way ANOVA) and P(a,CO2) was increased (group 2; P < 0.05; Student's t test). When rats breathed an air mixture containing 7 % CO(2) during sleep and wakefulness, .V(E) and V(T) were lower (groups 1 and 2; P < 0.001; ANOVA) and the Delta.V(E) in air containing 7 % CO(2) compared to air was decreased by 28-30 % (group 1) and 17-22 % (group 2). SP-SAP-treated rats also slept less during air breathing. We conclude that neurons with NK1R-ir somata or processes in the RTN/Ppy region are either chemosensitive or they modulate chemosensitivity. They also provide a tonic drive to breathe and may affect arousal.

Animals↗
PubMed2002

Capsaicin regulates vascular endothelial cell growth factor expression by modulation of hypoxia inducing factor-1alpha in human malignant melanoma cells.

PURPOSE: Capsaicin (8-Methyl-N-Vanillyl-6-nonenamide), a known natural dietary chemopreventive agent, inhibits malignant melanoma cell proliferation. In the present study, we examined the effect of capsaicin on constitutive and induced vascular endothelial cell growth factor (VEGF) expression in malignant melanoma cells. RESULTS: Capsaicin treatment resulted in enhanced VEGF protein secretion in malignant melanoma cells independent of IL-1beta and TNF-alpha. The observed up-regulation of VEGF production by capsaicin was concentration- and duration-dependent and was inversely associated with inhibition of melanoma cell proliferation. We observed an increase in hypoxia-inducible factor (HIF)-1alpha and VEGF mRNA expression in capsaicin-treated melanoma cells. Further, an electrophoretic mobility shift assay (EMSA) from nuclear extracts from melanoma cells showed a decrease in constitutive activation of NF-kappaB and enhanced HIF-1alpha binding activity to hypoxia response element (HRE) in melanoma cells treated with different concentrations of capsaicin. CONCLUSIONS: These data suggest that inhibition of cellular proliferation by capsaicin follows enhanced VEGF production by remaining melanoma cells by enhancing HIF-1alpha expression and binding to HRE.

Capsaicin↗
PubMed2002

The retrotrapezoid nucleus (RTN): local cytoarchitecture and afferent connections.

The retrotrapezoid nucleus (RTN) provides a source of tonic drive to respiratory neurons and is one of many sites for central chemoreception. Here we evaluate in the rat the local neuronal cytoarchitecture in the RTN histologically 2-4 h after neurobiotin injection and the afferent connections to the RTN 24 h after injection. Our neurobiotin injections often overlapped the RTN and the adjacent neurons of the parapyramidal region, so we group these two regions together in this study. The RTN is made up of small and medium sized neurons and has a low neuronal density compared to other nuclei. The organization of the RTN is reticular in nature and there are prominent small neurons at the ventral medullary border. Adjacent to the pyramids there are medium sized neurons with connections to the raphé pallidus. Major afferent connections include the regions of the dorsal and ventral respiratory groups, the medullary raphé, the contralateral parapyramidal and RTN regions, portions of the nucleus paragigantocellularis lateralis, and portions of the reticular fields. Other sources of input include the Kölliker-fuse nucleus, subceruleus, A5 region, and the paralemniscal zone.

Animals↗
PubMed2002

Ventral medulla pHi measured in vivo by 31P NMR is not regulated during hypercapnia in anesthetized rat.

Chemoreceptors in the ventral medulla contribute to the respiratory response to hypercapnia. Do they 'sense' intracellular pH (pHi)? We measured pHi in the ventral medulla or cortex (control) using 31P-NMR obtained via a novel 3 x 5 mm2 surface coil in anesthetized rats breathing air or 7% CO2. During air breathing over 240 min, pHi decreased slightly from 7.13 +/- 0.02 to 7.05 +/- 0.02 (SEM; n = 5; 2 cortex, 3 ventral medulla). During 180 min of hypercapnia, cortical pHi (n = 4) decreased from 7.17 +/- 0.02 to 6.87 +/- 0.01 by 90 min and recovered by 150 min. Ventral medulla pHi showed no such regulation. It decreased from 7.11 +/- 0.02 to 6.88 +/- 0.02 at 90 min and recovered only after cessation of hypercapnia (n = 5), results consistent with pHi being the chemoreceptor stimulus. However, non-chemoreceptor neurons that contribute to our medullary NMR signal also do not appear to regulate pHi in vitro. Regional differences in pHi regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons.

Adenosine Triphosphatases↗
PubMed2002

CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness.

To evaluate the function of widely distributed central chemoreceptors during sleep and wakefulness in the rat, we focally stimulate single chemoreceptor sites during naturally occurring sleep-wake cycles by microdialysis of artificial cerebrospinal fluid equilibrated with 25% CO2. In retrotrapezoid nucleus, this increased ventilation (tidal volume) by 24% only in wakefulness (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910-919, 1999). In caudal medullary raphé, it increased ventilation (frequency) by 15-20% only in sleep (Nattie EE and Li A. J Appl Physiol 90: 1247-1257, 2001). Here, in nucleus tractus solitarius (NTS), focal acidification significantly increased ventilation by 11% in sleep and 7% in wakefulness rostrally (n = 5) and by 16% in sleep and 28% in wakefulness caudally (n = 5). The sleep-wake cycle was unaltered. Dialysis with 5% CO2 had no effect. Dialysis with 50% CO2 caudally did not further stimulate ventilation but did disrupt sleep. Central chemoreceptors in the NTS affect breathing in both sleep and wakefulness. The threshold for arousal in caudal NTS is greater than that for the stimulation of breathing.

Acidosis↗