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In the central nervous system, tissue-type plasminogen activator (tPA) has been associated with both pro-death and prosurvival actions on neurons. In most cases, this has been related to exogenous tPA. In the present study, we addressed the influence of endogenous tPA. We first observed an increased transcription of tPA following either in vivo global brain ischemia in rats or in vitro oxygen glucose deprivation (OGD) on mice and rats hippocampal slices. Hippocampal slices from tPA-deficient mice were more sensitive to OGD than wild-type slices. Pharmacological approaches targeting the known receptors of tPA revealed that only the inhibition of phosphorylation of epidermal growth factor receptors (EGFRs) prevented the neuroprotective effect of endogenous tPA. This study shows that ischemic hippocampal neurons overproduce endogenous tPA as an intend to protect themselves from ischemic death, by a mechanism involving an activation of EGFRs. Thus, strategies contributing to promote either endogenous production of tPA or its associated EGFR-linked signaling pathway may have beneficial effects following brain injuries such as stroke.

We studied the potential neuroprotective effects of halothane and desflurane, compared with the awake state, on infarct size following 2 h of intraluminal middle cerebral artery occlusion (MCAo) and 22 h of reperfusion.

Background. We compared the cardioprotective effects of 1 minimum alveolar concentration (MAC) desflurane administered before, during or after ischaemia, or throughout the experiment (before, during and after ischaemia) on myocardial infarct size following 30 min occlusion of the left anterior descending coronary artery and 3 h reperfusion in adult rats. Methods. Fifty male Sprague–Dawley rats were anaesthetized with pentobarbital, intubated and mechanically ventilated. Blood gases, pH and body temperature (37.5–38°C) were controlled. Heart rate and arterial pressure were measured continuously. Animals were randomly assigned to the following groups (n=10 in each group): pentobarbital only (‘Pento’); 15 min desflurane administration followed by 10 min of washout before 30 min ischaemia and 3 h reperfusion (‘Precond’); 30 min desflurane administration during ischaemia period (‘Isch’); desflurane administration during the 15 first min of reperfusion (‘Reperf’) and desflurane administration throughout the experiment (before, during and after ischaemia; ‘Long’). Volumes at risk and infarct sizes were assessed by Indian ink and with 2,3,5‐triphenyltetrazolium chloride staining, respectively. Results. Physiological parameters and volumes at risk were not significantly different between groups. In the Pento group, mean myocardial infarct size was 65 (sd 15)% of the volume at risk; myocardial infarct size was reduced to a significant and comparable extent in the desflurane‐treated groups (Precond 42 (14)%; Isch 34 (11)%; Reperf 41 (15)%; Long 33 (10)%; P<0.0002 vs Pento group). Conclusions. In rats, desflurane 1 MAC significantly decreased myocardial infarct size whatever the period and duration of administration. Br J Anaesth 2004; 92: 552–7