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The cerebral pressure reactivity index (PRx), through intracranial pressure (ICP) measurements, informs clinicians about the cerebral autoregulation (CA) status in adult-sedated patients with traumatic brain injury (TBI). Using PRx in clinical practice is currently limited by variability over shorter monitoring periods. We applied an innovative method to reduce the PRx variability by ventilator-induced slow (1/min) positive end-expiratory pressure (PEEP) oscillations. We hypothesized that, as seen in a previous animal model, the PRx variability would be reduced by inducing slow arterial blood pressure (ABP) and ICP oscillations without other clinically relevant physiological changes. Patients with TBI were ventilated with a static PEEP for 30 min (PRx period) followed by a 30-min period of slow [1/min (0.0167 Hz)] +5 cmH 2 O PEEP oscillations (induced ( i PRx period). Ten patients with TBI were included. No clinical monitoring was discontinued and no additional interventions were required during the i PRx period. The PRx variability [measured as the standard deviation (SD) of PRx] decreased significantly during the i PRx period from 0.25 (0.22-0.30) to 0.14 (0.09-0.17) ( P = 0.006). There was a power increase around the induced frequency (1/min) for both ABP and ICP ( P = 0.002). In conclusion, 1/min PEEP-induced oscillations reduced the PRx variability in patients with TBI with ICP levels <22 mmHg. No other clinically relevant physiological changes were observed. Reduced PRx variability might improve CA-guided perfusion management by reducing the time to find "optimal" perfusion pressure targets. Larger studies with prolonged periods of PEEP-induced oscillations are required to take it to routine use. NEW & NOTEWORTHY Cerebral autoregulation assessment requires sufficient slow arterial blood pressure (ABP) waves. However, spontaneous ABP waves may be insufficient for reliable cerebral autoregulation estimations. Therefore, we applied a ventilator "sigh-function" to generate positive end-expiratory pressure oscillations that induce slow ABP waves. This method demonstrated a reduced variability of the pressure reactivity index, commonly used as continuous cerebral autoregulation measure in a traumatic brain injury population.

In the core of a brain infarct, loss of neuronal function is followed by neuronal death within minutes. In an area surrounding the core (penumbra), some perfusion remains. Here, neurons initially remain structurally intact, but massive synaptic failure strongly reduces neural activity. Activity in the penumbra may eventually recover or further deteriorate toward massive cell death. Besides activity recovery, return of brain functioning requires restoration of connectivity. However, low activity has been shown to initiate compensatory mechanisms that affect network connectivity. We investigated the effect of transient hypoxia and compensatory mechanisms on activity and functional connectivity using cultured cortical networks on multielectrode arrays. Networks were exposed to hypoxia of controlled depth (10-90% of normoxia) and duration (6-48 h). First, we determined how hypoxic depth and duration govern activity recovery. Then, we investigated connectivity changes during and after hypoxic incidents, mild enough for activity to recover. Shortly after hypoxia onset, activity and connectivity decreased. Following 4-6 h of ongoing hypoxia, we observed partial recovery. Only if the hypoxic burden was limited did connectivity show further recovery upon return to normoxia. Partial recovery during hypoxia was dominated by restored baseline connections, rather than newly formed ones. Baseline strengths of surviving (persisting or recovered) and lost connections did not differ nor did baseline activity at their "presynaptic" electrodes. However, "postsynaptic" electrodes of surviving connections were significantly more active during baseline than those of lost connections. This implies that recovery during hypoxia reflects an effective mechanism to restore network activity, which does not necessarily conserve prehypoxia connectivity. NEW & NOTEWORTHY Hypoxia reduced the firing rates of cultured neurons. Depending on hypoxic depth and duration, activity recovered during hypoxia and upon return to normoxia. Recovery (partial) during hypoxia was associated with restored baseline connections rather than newly formed ones. Predominantly, baseline connections with most active postsynaptic electrodes recovered, supporting the notion of effective activity homeostasis. This compensatory mechanism remained effective during ~20 h of hypoxia. Beyond 20 h of compensation, loss of activity and connectivity became irreversible., (Copyright © 2017 the American Physiological Society.)

In this study we measured urethral pressure changes in response to efferent pudendal nerve stimulation in rats. All other neural pathways to the urethra were transected, and the urethra was continuously perfused. We found fast twitch-like contractions, superimposed on a slow relaxation. The amplitude of the twitches was independent of the stimulation frequency below 26 Hz, whereas the relaxation depended highly on this frequency. The twitches were caused by striated urethral muscles, and the relaxation was caused by smooth muscles. Both were mediated by acetylcholine. We calculated the effective urethral relaxation as the absolute relaxation multiplied by the time fraction between the twitches. Maximum effective relaxation occurred at 8-10 Hz, exactly the frequency of spontaneous oscillations during bladder voiding in rats. Although the oscillatory sphincter contractions in rats during voiding may be needed in other mechanisms for efficient voiding, our data suggest that they may be a side effect of the actual purpose: urethral relaxation.

In this study, the mechanism involved in the initiation of voiding was investigated. Bladder pressure and bladder and urethral nerve activity were recorded in the anesthetized rat. Bladder nerve activity was resolved into afferent and efferent activity by means of a theoretical model. The beginning of an active bladder contraction was defined as the onset of bladder efferent firing at a certain time (t0). From t0 onward, bladder efferent activity increased linearly during deltat seconds (rise time) to a maximum. The pressure at t0 was 1.0 +/- 0.4 kPa, the afferent nerve activity at t0 was 2.0 +/- 0.6 microV (53 +/- 15% of maximum total nerve activity), and deltat was 11 +/- 13 s. Between contractions the afferent activity at t0 was never exceeded. Urethral afferent nerve activity started at bladder pressures of 2.1 +/- 1.1 kPa. Therefore, we concluded that urethral afferent nerve activity does not play a role in the initiation of bladder contractions; voiding contractions presumably are initiated by bladder afferent nerve activity exceeding a certain threshold.

In male urethan-anesthetized rats, activity was measured in nerves that run over the proximal urethra. The urethral nerve response to stepwise urethral perfusion could be described by a four-parameter model (fit error < 6%). At the onset of perfusion, the urethra was closed and the pressure increased with the infused volume. The nerve activity (NA) increased linearly with this inserted volume to a maximum (NAmax), which was proportional to the instantaneous pressure. The duration of this first episode (delta t) was inversely proportional to the perfusion rate. After infusion of a fixed volume, the urethra opened and the NA decreased with a time constant phi -1 (approximately 1.8 s) to an elevated level (NAlevel). NAlevel was linearly related to the steady-state pressure. Accordingly, sensors in the urethra are sensitive to pressure rather than to the perfusion rate. The parameters NAmax, NAlevel, and delta t showed very good reproducibility (SD approximately 19% of mean). The measured activity was most likely afferent and conducted to the major pelvic ganglion.