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Cardio-respiratory coupling is reflected as respiratory sinus arrhythmia (RSA) and inspiratory-related bursting of sympathetic nerve activity. Inspiratory-related inhibitory and/or postinspiratory-related excitatory drive of cardiac vagal motoneurons (CVMs) can generate RSA. Since respiratory oscillations may depend on synaptic inhibition, we investigated the effects of blocking glycinergic neurotransmission (systemic and local application of the glycine receptor (GlyR) antagonist, strychnine) on the expression of the respiratory motor pattern, RSA and sympatho-respiratory coupling. We recorded heart-rate, phrenic, recurrent laryngeal and thoracic sympathetic nerve activities (PNA, RLNA, t-SNA) in a working-heart-brainstem preparation of rats, and show that systemic strychnine (50–200 ​nM) abolished RSA and triggered a shift of postinspiratory RLNA into inspiration, while t-SNA remained unchanged. Bilateral strychnine microinjection into the ventrolateral medullary area containing CVMs and laryngeal motoneurons (LMNs) of the nucleus ambiguus (NA/CVLM), the nucleus tractus solitarii, pre-Bötzinger Complex, Bötzinger Complex or Kölliker-Fuse nuclei revealed that only NA/CVLM strychnine microinjections mimicked the effects of systemic application. In all other target nuclei, except the Bötzinger Complex, GlyR-blockade attenuated the inspiratory-tachycardia of the RSA to a similar degree while evoking only a modest change in respiratory motor patterning, without changing the timing of postinspiratory-RLNA, or t-SNA. Thus, glycinergic inhibition at the motoneuronal level is involved in the generation of RSA and the separation of inspiratory and postinspiratory bursting of LMNs. Within the distributed ponto-medullary respiratory pre-motor network, local glycinergic inhibition contribute to the modulation of RSA tachycardia, respiratory frequency and phase duration but, surprisingly it had no major role in the mediation of respiratory-sympathetic coupling., Graphical abstract Image 1, Highlights • Glycinergic inhibition controls inspiratory tachycardia via inhibition of cardiac vagal motoneurons. • Glycinergic inhibition controls the discharge pattern of expiratory laryngeal motoneurons. • Glycinergic neurotransmission has no major role in pattern formation at the pre-motor level. • Glycinergic inhibition has no role in sympatho-respiratory coupling.

ObjectiveTo assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD).MethodsWe combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed.ResultsOf 1,958 patients with CeAD (mean ± SD age 44.3 ± 10 years, 43.9% women), 1,588 (81.1%) had single nonrecurrent CeAD, 340 (17.4%) had multiple CeAD, and 30 (1.5%) presented with single CeAD at admission and had early recurrent CeAD. Patients with multiple or early recurrent CeAD did not significantly differ with respect to putative risk factors, clinical presentation, and outcome. In multivariable analyses, patients with multiple or early recurrent CeAD more often had recent infection (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.29–2.53), vertebral artery dissection (OR 1.82, 95% CI 1.34–2.46), family history of stroke (OR 1.55, 95% CI 1.06–2.25), cervical pain (OR 1.36, 95% CI 1.01–1.84), and subarachnoid hemorrhage (OR 2.85, 95% CI 1.01–8.04) at initial presentation compared to patients with single nonrecurrent CeAD. Patients with multiple or early recurrent CeAD also had a higher incidence of cerebral ischemia (hazard ratio 2.77, 95% CI 1.49–5.14) at 3 to 6 months but no difference in functional outcome compared to patients with single nonrecurrent CeAD.ConclusionPatients with multiple and early recurrent CeAD share similar risk factors, clinical characteristics, and functional outcome. Compared to patients with single nonrecurrent CeAD, they are more likely to have recurrent cerebral ischemia at 3 to 6 months, possibly reflecting an underlying transient vasculopathy.

The core circuit of the respiratory central pattern generator (rCPG) is located in the ventrolateral medulla, especially in the pre-Bötzinger complex (pre-BötC) and the neighboring Bötzinger complex (BötC). To test the hypothesis that this core circuit is embedded within an anatomically distributed pattern-generating network, we investigated whether local disinhibition of the nucleus tractus solitarius (NTS), the Kölliker-Fuse nuclei (KFn), or the midbrain periaqueductal gray area (PAG) can similarly affect the respiratory pattern compared to disinhibition of the pre-BötC/BötC core. In arterially-perfused brainstem preparations of rats, we recorded the three-phase respiratory pattern (inspiration, post-inspiration and late-expiration) from phrenic and vagal nerves before and after bilateral microinjections of the GABA(A)R antagonist bicuculline (50 nl, 10 mM). Local disinhibition of either NTS, pre-BötC/BötC, or KFn, but not PAG, triggered qualitatively similar disruptions of the respiratory pattern resulting in a highly significant increase in the variability of the respiratory cycle length, including inspiratory and expiratory phase durations. To quantitatively analyze these motor pattern perturbations, we measured the strength of phase synchronization between phrenic and vagal motor outputs. This analysis showed that local disinhibition of all brainstem target nuclei, but not the midbrain PAG, significantly decreased the strength of phase synchronization. The convergent perturbations of the respiratory pattern suggest that the rCPG expands rostrally and dorsally from the designated core but does not include higher mid-brain structures. Our data also suggest that excitation-inhibition balance of respiratory network synaptic interactions critically determines the network dynamics that underlie vital respiratory rhythm and pattern formation.

Objective:In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged ≥60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged Methods:We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i.e., Cervical Artery Dissection and Ischemic Stroke Patients–Plus consortium). We dichotomized cases into 2 groups, age ≥60 and Results:Among 2,391 patients diagnosed with CeAD, we identified 177 patients (7.4%) aged ≥60 years. In this age group, cervical pain (ORadjusted 0.47 [0.33–0.66]), headache (ORadjusted 0.58 [0.42–0.79]), mechanical trigger events (ORadjusted 0.53 [0.36–0.77]), and migraine (ORadjusted 0.58 [0.39–0.85]) were less frequent than in younger patients. In turn, hypercholesterolemia (ORadjusted 1.52 [1.1–2.10]) and hypertension (ORadjusted 3.08 [2.25–4.22]) were more frequent in older patients. Key differences between age groups were confirmed in secondary analyses. In multivariable, adjusted analyses, favorable outcome (i.e., modified Rankin Scale score 0–2) was less frequent in the older age group (ORadjusted 0.45 [0.25, 0.83]).Conclusion:In our study population of patients diagnosed with CeAD, 1 in 14 was aged ≥60 years. In these patients, pain and mechanical triggers might be missing, rendering the diagnosis more challenging and increasing the risk of missed CeAD diagnosis in older patients.