ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression and the subcellular localization of HDAC9 in different brain regions of mice after cerebral ischemic injury and explore the association between HDAC9 and ischemic stroke.</p><p><b>METHODS</b>Twenty-one male C57BL/6 mice were randomly divided into sham-operated group (n=9) and operated group (n=12). In the latter group, the mice with Zea-Longa neurological deficit scores of 2 or 3 following middle cerebral artery occlusion (MCAO) were assigned into MCAO group (n=9). Immunofluorescence was performed to investigate the subcellular localization of HDAC9 in the brain tissues on day 3 after MCAO. Western blotting and qRT-PCR were used to analyze the expression of HDAC9 in different regions of the brain. Results Immunofluorescence showed more intense HDAC9 expressions in the brain tissues around the infarct focus, and in the cells surrounding the infarct, HDAC9 expression was obviously increased in the cytoplasm and reduced in the cell nuclei. Compared with the other brain regions, the ipsilesional cortex with MCAO showed more abundant HDAC9 expressions at both the mRNA and protein levels (P<0.05).</p><p><b>CONCLUSION</b>HDAC9 may be closely related to cerebral ischemic injury and participate in the pathophysiological process of ischemic stroke.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To explore the pharmacokinetics of amphotericin B (AMB) in the cerebrospinal fluid (CSF) during continuous intrathecal administration of AMB for treatment of cryptococcal neoformans meningitis (CNM).</p><p><b>METHODS</b>The concentration of AMB in the CSF was measured using reversed phase high performance liquid chromatography (RP-HPLC) in 3 patients receiving continuous intrathecal infusion of AMB for CNM.</p><p><b>RESULTS</b>AMB concentrations in the CSF of the 3 patients exceeded the minimal inhibitory concentration (MIC) of AMB against Cryptococcus neoformans. The concentration-time curve showed that AMB concentration in the CSF underwent obvious variations on the first day of intrathecal infusion and after additional AMB doses, but maintained a stable level (0.61-1.21 µg/ml) on the next day.</p><p><b>CONCLUSION</b>[corrected] Continuous intrathecal administration of AMB can enhance the drug concentration in the CSF and maintain a stable and effective drug level for treatment of CNM.</p>
Subject(s)
Adolescent , Female , Humans , Male , Amphotericin B , Pharmacokinetics , Antifungal Agents , Pharmacokinetics , Cerebrospinal Fluid , Metabolism , Cryptococcus neoformans , Infusions, Spinal , Methods , Meningitis, Cryptococcal , Drug Therapy , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To establish a rat model of focal lymphatic encephalopathy by partial ligation of the cerebral superficial artery for observation of the changes of Virchow-Robin spaces (VRS).</p><p><b>METHODS</b>Thirty male SD rats were randomized into 3 groups (n=10), including two model groups and a sham-operated group. The rats in the model groups were subjected to partial ligation of the cerebral superficial arteries under EEG monitoring to induce focal lymphatic encephalopathy, and those in the sham-operated group underwent only dissociation of the cerebral superficial artery without ligation. The rats in the two model groups were executed at 24 and 48 h, and those in the sham-operated group at 48 h following the operation, respectively. Frozen sections of the brain tissues were prepared for microscopic morphological observation and quantitative analysis of the VRS using HE staining and an image analysis system, respectively.</p><p><b>RESULTS</b>EEG remained normal during the operations suggesting intact brain function. Partial ligation of the cerebral superficial arteries resulted in obvious dilation of the VRS in the cerebral cortex and subcortical medulla, and the tissues around the dilated VRSs appeared pale and structurally loosened. The two model groups showed significantly enlarged VRS areas as compared to the sham-operated group (P<0.01), but no significant differences were found in the mean VRS areas between the two model groups.</p><p><b>CONCLUSION</b>Partial dilation of the cerebral superficial artery is effective and convenient to induce focal lymphatic encephalopathy in rats, and this model can be ideal for studying focal cerebral lymph circulation.</p>
Subject(s)
Animals , Male , Rats , Brain Edema , Cerebral Arteries , General Surgery , Disease Models, Animal , Ligation , Lymphatic System , Random Allocation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study the protective effects of nerve growth factor (NGF) and Danshen on hippocampal neurons in gerbils (Meriones unguiculatus) with global ischemia-reperfusion injury.</p><p><b>METHODS</b>Global ischemia-reperfusion model was established in 54 male Z:ZCLA gerbils by occlusion of the bilateral carotid arteries. The animal models were randomized into 3 groups to receive treatment with normal saline, NGF, and Danshen 30 min after the reperfusion. At 6 h, 3 and 7 days after the reperfusion, the survival of the hippocampal CA1 pyramidal neurons was observed using optical and electron microscopy, and immunohistochemistry was employed to detect the expressions of Bcl-2 and Bax in the neurons.</p><p><b>RESULTS</b>Neuronal apoptosis was not observed in the hippocampus 6 h after the reperfusion, but at 3 and 7 days, the number of apoptotic neurons increased significantly in the CA1 region. Compared with normal saline, treatments with NGF and Danshen both significantly reduced the number of apoptotic neurons at 3 and 7 days. The number of apoptotic neurons showed no significant difference between NGF and Danshen treatment groups at 3 days, but at 7 days, the apoptotic cell number was significantly lower in NGF group (P<0.05). Bcl-2 expression was the highest in NGF group, and its highest expression occurred at 6 h after the reperfusion; Bax expression was detected in saline group, and underwent no significant changes with the passage of time.</p><p><b>CONCLUSION</b>Both NGF and Danshen show protective effects against global ischemia-reperfusion injury. NGF has a stronger protective effect than Danshen, and this finding provides experimental evidence for selecting appropriate protective agents in the treatment of ischemic brain damage.</p>