Isoflurane induces c-Fos expression in the area postrema of the rat.

INTRODUCTION: Volatile anesthetics are speculated to cause postoperative nausea and vomiting via stimulation of the chemoreceptor trigger zone (CTZ). However, the precise mechanism underlying the emetic action of these drugs is not well understood. In this study, we assessed whether isoflurane induced the expression of c-Fos, a neuronal activation marker, in the area postrema (AP), the locus of the CTZ, in rats, which do not have vomiting action. MATERIALS AND METHODS: Male rats were exposed to 1.3% isoflurane for 0-240 min, or to various concentrations of isoflurane (0, 1.3%, or 2.6%) for 120 min. Finally, the rats were exposed to 1.3% isoflurane for 120 min after ondansetron administration. After the treatments, immunohistochemistry of the rat AP was performed using c-Fos antibody staining. RESULTS: One-way analysis of variance showed that isoflurane exposure significantly increased c-Fos expression in the AP; however, the rats pretreated with 4 mg/kg ondansetron showed significantly decreased c-Fos expression. Moreover, we evaluated the effect of the anesthetic on inducing pica in the rats, and found that kaolin intake was not influenced by isoflurane exposure. CONCLUSION: Overall, these results suggest that isoflurane activates AP neurons and may be involved in the emetic mechanism of isoflurane. This study further suggests the feasibility of using rats as a model for studying emetic mechanisms of drugs, despite their lack of vomit action.

Influence of nitrous oxide on granule cell migration in the dentate gyrus of the neonatal rat.

For several decades, the neurotoxicities of anesthetics to the developing brain have been reported by many researchers focusing on various phenomena such as apoptosis, neurodegeneration, electrophysiological aberrations, and behavioral abnormalities. According to these reports, signals via N-methyl-D-aspartate receptors (NMDA-r) and/or γ-aminobutyric acid type A receptors (GABAA-r) are implicated in the anesthetic neurotoxicity. On the other hand, during brain development, NMDA-r and GABAA-r are also recognized to play primary roles in neural cell migration. Therefore, anesthetics exposed in this period may influence the neural cell migration of neonates, and increase the number of hilar ectopic granule cells, which are reported to be a cause of continuous neurological deficits. To examine this hypothesis, we investigated immunohistochemically granule cell distribution in the hippocampal dentate gyrus of Wistar/ST rats after nitrous oxide (N2O) exposure. At postnatal day (P) 6, 5-bromo-2'-deoxyuridine (BrdU) was administered to label newly generated cells. Then, rats were divided into groups (n = 6 each group), exposed to 50% N2O at P7, and evaluated at P21. As a result, we found that ectopic ratios (ratio of hilar/total granule cells generated at P6) were decreased in rats at P21 compared with those at P7, and increased in N2O exposed rats for over 120 min compared with the other groups. These results suggest that 50% N2O exposure for over 120 min increases the ratios of ectopic granule cells in the rat dentate gyrus.

Plantar injection of formalin in rats reduces the expression of a potassium chroride cotransporter KCC2 in the spinal cord and a kinase inhibitor suppresses this reduction.

Brain-derived neurotrophic factor (BDNF) is released from activated microglia during neuropathic pain and is hypothesized to downregulate the expression of the potassium chloride cotransporter 2 (KCC2) via the TrkB receptor. Previous studies reported that KCC2 is downregulated 5 min after the plantar injection of formalin in rats; however, the mechanism behind this decrease in KCC2 expression during acute inflammatory pain remains unknown. In this study, we determined whether the TrkB receptor contributes to the expression of KCC2 during the acute pain. Five minutes after the plantar injection of formalin in rats, the ratio of KCC2-immunoreactive area in layer II of the spinal cord significantly decreased on the stimulated side compared to the unaffected side. On the other hand, this response was inhibited by the injection of a kinase inhibitor, K252a, in the subarachnoid space 15 min before the formalin injection. These findings suggest that in acute pain, the TrkB receptor may contribute to the decrease in the expression of KCC2.

Co-existing liver disease increases the risk of postoperative thrombocytopenia in patients undergoing hepatic resection: implications for the risk of epidural hematoma associated with the removal of an epidural catheter.

PURPOSE: A common surgical diagnosis for hepatic resection in Japan is hepatocellular carcinoma secondary to chronic viral hepatitis. It is known that chronic liver disease causes a decrease in blood platelet count. We retrospectively reviewed the perioperative changes in blood platelet count associated with hepatic resection at a Japanese institution and evaluated the incidence and risk factors for postoperative thrombocytopenia, which may increase the potential risk of epidural hematoma. METHODS: We analyzed the data of 165 patients who underwent hepatic resection between 1 March 2010 and 30 June 2012 at Hokkaido University Hospital. The criterion of the platelet count for the unsafe removal of epidural catheter was <100,000/µL. Logistic regression was used to model the association between postoperative thrombocytopenia and co-existing liver disease, estimated blood loss and type of hepatic resection. RESULTS: After hepatic resection, 42.4 % of patients without preoperative thrombocytopenia experienced thrombocytopenia. The presence of co-existing liver disease was identified as a risk factor for postoperative thrombocytopenia [odds ratio 3.17 (95 % confidence interval 1.63-6.18)]. There was no epidural hematoma in the 149 patients who had epidural anesthesia. CONCLUSION: Hepatic resection can cause postoperative thrombocytopenia that may increase the potential risk of epidural hematoma associated with catheter removal, and the presence of co-existing liver disease heightens concerns for postoperative crucial thrombocytopenia.

[Coagulation profiles following donor hepatectomy and implications for the risk of epidural hematoma associated with epidural anesthesia].

BACKGROUND: Continuous epidural analgesia has become an accepted technique used in laparotomy including liver resections. Although American Society of Regional Anesthesia and Pain Medicine recommends that epidural catheter be removed with prothrombin time-international normalized ratio (PT-INR) less than 1.5, it is possible that liver surgery causes coagulation disturbances. We examined the postoperative changes in coagulation profiles of living liver donors to elucidate whether hepatectomy increases the risk of epidural hematoma related to removal of epidural catheters or not. METHODS: From January 2007 to October 2009, 42 living liver related transplantations were performed in Hokkaido University Hospital. We reviewed the donor data including PT-INR obtained during perioperative days [preoperative, immediately postoperative, postoperative day 1, 3 and 7] and epidural catheter-related-complications, retrospectively. RESULTS: While in all donors values of PT-INR obtained during preoperative periods were within normal limits, 14 donors had a PT-INR over 1.5 during postoperative periods. There was no epidural hematoma case in this study. CONCLUSIONS: Our study suggested that hepatectomy increases the risk of epidural hematoma related to removal of epidural catheters, even in the living liver transplant donors with normal liver function.