Monitoring of CBFV and time characteristics of oxygen-induced acute CNS toxicity in humans.

BACKGROUND: Hyperbaric oxygen can cause central nervous system (CNS) toxicity with seizures. We tested the hypothesis that CNS toxicity could be predictable by cerebral blood flow velocity (CBFV) monitoring. METHOD: We monitored 369 mandatory oxygen tolerance tests (30 min, 280 kPa O(2)) by video-documentation and since May 2005 by additional CBFV registration (n = 61). RESULTS: The onset of early manifestations of CNS toxicity was documented in 11 of 369 tests within 22 +/- 3 min. These included twitches and/or agitation, 6 of 11 and tonic-clonic seizures in 5 of 11 cases. In both cases with CBFV monitoring, an increase in CBFV preceded symptom onset, once followed by seizure, once without seizure after timely oxygen reduction. CONCLUSIONS: During exposure to 280 kPa oxygen at rest a constant delay of approximately 20 min precedes the onset of central nervous oxygen toxicity. An increase in CBFV may indicate the impending seizure.

Neuroprotection by oxygen in acute transient focal cerebral ischemia is dose dependent and shows superiority of hyperbaric oxygenation.

The neuroprotective effect of oxygen after acute stroke in rats has been shown previously. However, the question of optimal dosing still remains unanswered. Thus, we investigated the use of oxygen at different concentrations by either normobaric oxygenation (NBO) or hyperbaric oxygenation (HBO) at different pressures in a model of transient ischemia/reperfusion in rats. Animals underwent 90 min of middle cerebral artery occlusion (MCAO) followed by 90 min of reperfusion before oxygen treatment. Oxygen was applied either by NBO (100% O(2); 1.0 absolute atmosphere, ATA) or HBO (100% O(2); 1.5, 2.0, 2.5 or 3.0 ATA) for 1 h. Primary endpoints were infarct volume and clinical outcome measured 24 h and 7 days following the MCAO. A statistically significant and long-lasting reduction in infarct volume was seen in the HBO 2.5 ATA and 3.0 ATA groups over a period of 7 days. The reduced infarct volume was accompanied with a statistically significant improvement in clinical outcome in the high-dose oxygen-treated groups. The presented data indicate that oxygen is a highly neuroprotective molecule in transient focal cerebral ischemia in rats, when applied early and at high doses. The effect is dose dependent and shows a superiority of HBO over NBO, when the primary endpoints infarct volume reduction and clinical outcome are analyzed. These data are important for the development of new acute stroke treatment studies in humans.

Platelet-leukocyte interaction and platelet activation in acute stroke with and without preceding infection.

OBJECTIVE: Acute coronary syndromes and ischemic cerebral stroke share similarities regarding elevated platelet activation. In coronary syndromes, the importance of inflammation with platelet-leukocyte interaction has been demonstrated. Recent infection is an established risk factor for ischemic stroke; the role of platelet-leukocyte interaction in these patients had not been investigated. METHODS AND RESULTS: Using a flow cytometric assay we investigated 58 stroke patients, 21 with and 37 without infection 1 week before acute cerebral ischemia, and compared them to 58 controls with regard to platelet-leukocyte aggregation and platelet activation on admission and on day 7. Patients with previous infection were significantly up-regulated with regard to platelet activation and platelet-leukocyte aggregation compared with patients without infection. On day 7, these increases in the postinfective group had drawn level with the lower values of the other patients. As reported previously, recent infection was associated with a more severe postischemic deficit. CONCLUSIONS: These results suggest an important role of intercellular platelet-leukocyte interaction in the pathophysiology of acute cerebral ischemia which may also contribute to the increased incidence and clinical severity of ischemic stroke following infection. This may lead to therapeutic considerations of blocking intercellular adhesion molecules like P-selectin or the P-selectin glycoprotein ligand.

Alterations of cortical electrical activity in patients with sacral neuromodulator.

OBJECTIVES: Sacral neuromodulation represents chronic stimulation of the sacral (S3) nerve. So far, the mode of action and neuro-anatomical basis is unclear. Sacral reflex mechanisms as well as pontine or cortical centers of modulation have been postulated. Our aim was to evaluate possible alterations in electroencephalogram (EEG) activity as an indicator of a supraspinally mediated mechanism of sacral neuromodulation. MATERIALS AND METHODS: We analyzed serial EEGs (apparatus: Kölner Vitaport System) using electrodes placed at Fz, Cz, Cz' and Pz in 10 patients. Subsequently, the sacral (S3) nerve was stimulated by means of an impulse generator (Medtronic, Interstim 3023) using an on-off paradigm with a 1.5s "on" interval followed by a 10s stimulation break. Raw data were analyzed using both Matlab 4.0 software and a specially developed averaging routine. RESULTS: All patients demonstrated a cortical potential complex following sacral root stimulation with an early electronegative component at 50 ms with a mean amplitude of 23 microV followed by a late potential component with a mean latency of 253 ms and a mean amplitude of 5 microV, both with a maximum at Cz, corresponding to the post-central gyrus. This finding occurred irrespective of patient's reports of actually feeling the neuromodulator being switched on and off. CONCLUSION: In neuromodulation responders, both short and long latency cortical potentials can be reproduced with a maximum at the sensory cortical area. Although these potentials are similar to cognitively mediated "event-related potentials", they are clearly distinct from any subjective sensory or even painful response since several patients of this series have not been able to feel any neuromodulator action. Therefore, this pilot study indicates a supraspinally mediated site of modulation, most probably in sensory cortex areas.

Involvement of substance P in ultraviolet irradiation-induced inflammation in rat skin.

The possible involvement of substance P released from primary afferents in rat skin was investigated in cutaneous inflammation following ultraviolet (UV) irradiation. Recordings from c-fibres innervating the UV-exposed hindpaw skin showed long-lasting low-frequency (0.8-1.25 Hz) spontaneous activity. Spontaneously active c-fibres increased to constitute 35.3% of the total population 72 h after UV exposure. Immunohistochemical analysis of substance P-containing nerve fibres in hindpaw skin revealed a significant increase in substance P immunoreactivity 24 h after UV irradiation. Average length of substance P-immunolabelled nerve fibres was about two times higher in UV-exposed compared to control skin. UV-induced oedema was investigated in rat ears using an ear-swelling test. Intradermal injection of either peptide (Spantide) or nonpeptide (CP-96,345) substance P antagonists and epicutaneous application of CP-96,345 reduced UV-induced oedema significantly in the late phase of sunburn (> 12 h after UV exposure). The UV-induced increase in skin blood flow was investigated in hindpaw skin up to 72 h by the laser Doppler technique. Epicutaneous application of CP-96,345 reduced erythema significantly between 12 and 72 h after UV exposure. Thus, our findings suggest the involvement of neurogenic substance P as a proinflammatory mediator in the late phase of UV-induced cutaneous inflammation in rats.