Increased cyclin D1 in vulnerable neurons in the hippocampus after ischaemia and epilepsy: a modulator of in vivo programmed cell death?

Several observations suggest that delayed neuronal death in ischaemia, epilepsy and other brain disorders includes an apoptotic component, involving programmed cell death (PCD). PCD is hypothesized to result, in part, from aberrant control of the cell cycle. Because they are instrumental in mitosis, cyclins D are key markers to evaluate whether neurons indeed progress into the cell cycle in situations of pathology. Therefore, we investigated in rat brains, the expression of cyclins D in the delayed neuronal death that occurs following transient global ischaemia and kainate-induced seizures. Following a four-vessel occlusion insult, quantitative in situ hybridization revealed a highly significant and persistent 100% increase of cyclin D1 mRNA in the vulnerable pyramidal neurons of the CA1 hippocampal region. Ischaemia also induced a smaller and transient cyclin D1 mRNA increase in the resistant CA3 area and dentate gyrus. In contrast, the cyclin D2 and D3 mRNAs, expressed constitutively in the adult rat hippocampus, were not upregulated. Following kainate-induced seizures, cyclin D1 mRNA was induced in the vulnerable CA3 region, and to a lesser extent, in non-vulnerable regions. Cyclin D1 immunohistochemistry revealed increased protein levels in the cytoplasm and nucleus of neurons commited to die after ischaemia. Double labelling experiments indicate that cyclin D1 is also expressed in reactive astrocytes but not in microglial cells. Finally, we report that in neurons, cyclin D1 expression peaks before nuclear condensation and the appearance of DNA fragmentation. We propose that cyclin D1, when expressed at high levels in lesioned neurons, may act as a modulator of apoptosis.

Transcutaneous cranial electrical stimulation (Limoge's currents) decreases early buprenorphine analgesic requirements after abdominal surgery.

Transcutaneous cranial electrical stimulation with Limoge's currents (TCES) consists of high frequency, low intensity currents which decreased anesthetic requirements during elective surgery. This action is likely to be mediated by the release of central endogenous opioids. In the present study, we hypothesized that TCES applied intraoperatively may decrease early postoperative narcotic requirements. Thirty-nine ASA physical status I and II patients undergoing elective abdominal surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled study. Just before induction of anesthesia, patients were connected to the electrical stimulator and randomly allocated to be either stimulated (TCES group, n = 20) or not (control group, n = 19) during surgery. The managing anesthesiologist was unaware of which group the patient was assigned. Postoperatively, patients were given a patient-controlled analgesia (PCA) device delivering buprenorphine for the first four postoperative hours. The recorded variables included postoperative buprenorphine requirements, pain scores (0-10 visual analog scale [VAS]), sedation (0-4 scale), and intraoperative isoflurane requirements. Patients were comparable with respect to age, sex ratio, weight, duration of surgery, intraoperative hemodynamics, fentanyl requirements, and time from skin closure to tracheal extubation. Buprenorphine requirements were significantly reduced in the TCES group versus the control group (2.36 vs 3.43 micrograms.kg-1.h-1; P = 0.002). Intraoperative isoflurane anesthetic requirements, as well as hourly postoperative scores for pain and sedation, were the same for the two groups. These data indicate that TCES reduces narcotic requirements for early postoperative analgesia. This technique might have potential to facilitate early postoperative analgesia in patients undergoing elective abdominal surgery.

[Pocket informatics in anesthesia]. / L'informatique de poche en anesthésie.

A simple, easy to use and inexpensive computerized system could optimize the evaluation of anaesthetic activities. Full processing of information remains our ideal but its difficulties and cost make it hardly possible yet. On the other hand, each anaesthetist can use, for example, a pocket Psion Computer which allows to register 15 items for each anaesthesia. All data are subsequently transferred to a Macintosh central computer. However this activity recording cannot be a substitute for the medical anaesthesia chart which remains essential.