Cerebral reactive oxygen species assessed by electron spin resonance spectroscopy in the initial stage of ischemia-reperfusion are not associated with hypothermic neuroprotection.

Using an in vivo L-band electron spin resonance (ESR) system, we determined changes in reactive oxygen species (ROS) levels during the early stage (within 60 minutes) of global cerebral ischemia-reperfusion (IR) under normothermic and hypothermic conditions in rats. To confirm the neuroprotective role of hypothermia in this IR model, we immunohistochemically evaluated the levels of active caspase-3 in the hippocampal CA1 sector. ROS levels increased within the first 15 minutes following IR under both normothermic and hypothermic conditions; however, the ROS levels did not differ significantly between normothermic and hypothermic conditions. In the later periods of IR, there were no significant changes in ROS levels for either normothermic or hypothermic conditions relative to the control. As expected, normothermia increased the number of active caspase-3 immunoreactive nuclei in the IR model. However, this induction was prevented by hypothermia. These results suggest that the neuroprotective role of hypothermia does not correlate with the early ROS-induced oxidative stress following IR as measured by ESR.

Use of moderate sedation for a patient with Down syndrome, intellectual disability, and Eisenmenger syndrome: a case report.

For patients who have Eisenmenger syndrome (ES), perioperative risks are high even for noncardiac surgery, such as dental extractions. We report on the case history of a 38-year-old male patient with Down syndrome (DS), intellectual disability (ID), and ES. The patient was scheduled for extraction of the right maxillary second molar tooth. His physical health was poor. Following oxygenation, midazolam was administered intravenously very slowly until the optimum sedative level was obtained, with a total dosage of 3.5 mg. There were no marked changes in vital signs during the perioperative period, and the patient was discharged the same day. This case suggests that moderate or conscious sedation using midazolam for dental treatment of a patient with DS, ID, and ES was well tolerated. Several critical points are presented in this review.

Immunohistochemical localization of chemokine CXCL14 in rat hypothalamic neurons.

We immunohistochemically investigated the distribution of CXCL14, also called BRAK protein in the rat hypothalamus using anti-human CXCL14 serum. CXCL14-immunoreactive somata were localized in the periventricular area and paraventricular and supraoptic hypothalamic nuclei. In the former, immunoreactive neuronal somata, confirmed by double staining with a neuronal marker, NeuN, contained diffuse CXCL14-like immunoreactivity in their perikarya. In contrast, immunoreactive somata in the latter contained immunoreactive puncta within their perikarya. Very dense immunoreactive fibers and puncta were seen in the median eminence. Dense immunoreactive fibers were seen in the arcuate nucleus and ventromedial hypothalamic nucleus. Other hypothalamic areas contained a few immunoreactive fibers and puncta. These results demonstrated for the first time that CXCL14 protein is present in a subset of hypothalamic neurons and suggest that CXCL14 participates in hypothalamic functions such as control of autonomic nervous systems and/or participates in immune cell recruitment via the median eminence.

Occlusal disharmony in mice transiently activates microglia in hippocampal CA1 region but not in dentate gyrus.

Occlusal disharmony is induced by various conditions such as the loss of teeth and inappropriate vertical dimension of crowns, bridges, or dentures. Occlusal disharmony sometimes causes indefinite complaint syndromes, which may be associated with astrocytic hypertrophy and the reduction of numbers of neuronal somata and their dendritic spines in the hippocampus. Microglia monitors the condition of neurons and responds to their degeneration accompanying with astrocytes. However, the effect of occlusal disharmony on the microglia has not yet been investigated. We artificially increased the occlusal vertical dimension by placing dental resin on the upper molars in mice and immunohistochemically investigated the effects of the increase in the vertical dimension on microglia of the hippocampal formation using an antibody against ionized calcium-binding adaptor molecule 1 (Iba-1), a marker protein for microglia. We measured the area occupied by Iba-1-immunoreactive microglia in the hippocampal CA1 region and dentate gyrus 1, 3, and 5 days after increasing the vertical dimension, and compared it with that of control mice. The hippocampal CA1 region contains vulnerable neurons and the dentate gyrus durable neurons. We found that the areas occupied by microglia in the hippocampal CA1 region increased, with the peak on the third day after increasing the vertical dimension, and it gradually declined by the fifth post-operative day. However, such an increase of the area occupied by microglia was not seen in the dentate gyrus. In conclusion, abnormal mastication may activate microglia in the area harboring vulnerable neurons, but not in the area harboring durable neurons.

Hypothermic and normothermic ischemia-reperfusion activate microglia differently in hippocampal formation.

Using immunohistochemical methods, we investigated microglial profiles under normothermic ischemia and hypothermic ischemia using an anti-ionized calcium-binding adapter molecule 1 (Iba-1) antibody. In the early stages of ischemia-reperfusion, Iba-1-immunoreactive microglial cells under normothermic ischemia were characterized by swollen somata with short and thick processes, while fine long-branched processes in greater numbers were seen emanating from microglial somata under hypothermic ischemia. In animals subjected to hypothermic ischemia, immunoreactive microglial areas in the hippocampal CA1 sector were significantly increased after 5 and 8 h of reperfusion when compared with those under normothermic ischemia. In the dentate gyrus, an increase in the microglial area under hypothermic ischemia was already evident at 2 h after reperfusion; this increased level was maintained up to 8 h. Considering the various neuroprotective roles of hypothermic ischemia, the characteristic features of microglia under hypothermic ischemia may be associated with the formation of a neuroprotective environment.

Measurement of cerebral reactive hyperemia at the initial post-ischemia reperfusion stage under normothermia and moderate hypothermia in rats.

Inhibition of the initial events occurring immediately after ischemia-reperfusion seems to be beneficial for reducing the extent of subsequent chronic neuronal cell injury. We investigated the effects of moderate hypothermia (32 degrees C) commencing 30 min before ischemia on reactive hyperemia by measuring cerebral blood flow (CBF) with a laser-Doppler flowmeter at the initial ischemia-reperfusion stage (60 min) following 10 min of global cerebral ischemia in rats. In normothermia, CBF was increased to approximately 240% and decreased thereafter, although it remained at approximately 150% after 60 min of ischemia-reperfusion. In contrast, hypothermia increased CBF to more than 270% after ischemia-reperfusion, then recovered to the basal level within 30 min. The period of reactive hyperemia under normothermia tended to be shortened by pre-administration of an NMDA antagonist, in a manner similar to hypothermia. Furthermore, hypothermia inhibited the presence of cells with caspase-3-like immunoreactivity in the hippocampal CA1 sector after 8 h of ischemia-reperfusion. Our findings indicate that hypothermia tends to shorten the period of reactive hyperemia during the initial ischemia-reperfusion stage. This phenomenon may be partly associated with activation of NMDA receptors and a beneficial effect of hypothermia in resisting progression of the neurotoxic cascade in the first 8 h after ischemia-reperfusion.

Usefulness of noninjectable anesthetic gel for intraperiodontal gingival retraction.

This study aimed to determine the efficacy of local anesthesia using Oraqix for gingival retraction in 35 healthy adult patients. The median visual analogue scale value was 20.5 +/- 24.2 (range: 0 to 81) for pain encountered during the procedure. In most patients, a lower verbal rating scale value corresponded with a lower visual analogue scale value. More than 80% of the operators evaluated the procedure as simple to perform, and more than 65% considered it useful compared with conventional injectable anesthesia. The results suggest that Oraqix is an attractive alternative to injectable anesthesia generally performed for gingival retraction at dental clinics.

Hypothermic, but not normothermic, ischemia causes a drastic increase in cyclooxygenase-2 immunoreactive granule cells in rat dentate gyrus after 4 hours of ischemic reperfusion.

We investigated cyclooxygenase-2 (Cox-2) immunoreactive cells in the hippocampus and dentate gyrus of Sprague-Dawley rats at 4 h after the induction of normothermic and hypothermic ischemia and reperfusion. Under the normothermic condition, Cox-2 immunoreactive cells showed more intense staining and clearer proximal dendrite configurations as compared with the control animals, whereas the numbers of immunoreactive cells in the hippocampus and dentate gyrus were not remarkably increased. In contrast to the normothermic condition, long-term (pre- and intra-ischemic) and short-term (exclusively intra-ischemic) hypothermic conditions caused a drastic increase in immunoreactive cells in the dentate gyrus. Nearly all granule cells were immuno-positive for Cox-2, whereas the CA3 and hilus sectors showed no remarkable increase in immunoreactive cell numbers. In sham-operated animals exposed to long-term hypothermia - but not ischemia, Cox-2 staining profiles were similar to those in the control animals. These results suggest that, for a drastic increase in Cox-2 immunoreactive granule cells to occur within a short time period (4 h), at a minimum, both hypothermia and ischemia, are required. Considering the neuroprotective roles of the hypothermia, a rapid increase in Cox-2 in the dentate gyrus might be associated with this temperature-sensitive phenomenon.