OBJECTIVETo investigate the cerebral uptake and regional distribution of propofol when plasma propofol concentration reaches equilibrium in the internal carotid artery and internal jugular vein in dogs.

METHODSEight male hybrid dogs aged 12-18 months weighing 10-12 kg were anesthetized with propofol at a single bolus (7 mg/kg) in 15 s followed by propofol infusion at a constant rate of 70 mg.kg(-1).h(-1) via the great saphenous vein of the right posterior limb. Blood samples were taken from the internal carotid artery and internal jugular vein at 30 min (T30) after propofol infusion for measurement of plasma propofol concentrations by high-pressure liquid chromatography (HPLC). The thalamus, epithalamus, metathalamus, hypothalamus, subthalamus, frontal lobe, parietal lobe, temporal lobe, hippocampus, cingulate gyrus, cerebellum, midbrain, pons, medulla oblongata and cervical cord were then dissected to determine propofol concentrations in these tissues by HPLC.

RESULTSThe propofol concentrations in the internal carotid artery and internal jugular vein blood plasma were comparable at T30 (6.16-/+1.02 vs 6.17-/+1.00 microg/ml, P>0.05). The propofol concentration was 6.11-/+1.07 microg/g in the epithalamus, 6.14-/+0.98 microg/g in the metathalamus, 6.12-/+1.02 microg/g in the hypothalamus, 6.15-/+1.00 microg/g in the subthalamus, 6.20-/+1.03 microg/g in the frontal lobe, 6.18-/+1.02 microg/g in the parietal lobe, 6.13-/+1.00 microg/g in the temporal lobe, 6.07-/+0.99 microg/g in the hippocampus, 6.14-/+1.06 microg/g in the cingulate gyrus, 6.15-/+1.00 microg/g in the cerebellum, 6.13-/+1.05 microg/g in the midbrain, 6.18-/+1.01 microg/g in the pons, 6.15-/+0.93 microg/g in the medulla oblongata, and 6.13-/+1.00 microg/g in the cervical cord, showing no significant differences in the distributions (P>0.05). Propofol concentration in the thalamus (8.68-/+0.88 microg/g) was significantly higher than those in the other brain tissues (P<0.05).

CONCLUSIONSAt the constant intravenous propofol injection rate of 70 mg.kg(-1).h(-1), plasma propofol concentration reaches equilibrium 30 min after the injection in the internal carotid artery and internal jugular vein with even distribution in the cerebral tissues in dogs, but the thalamus contains high propofol concentration.

Absorption ; Anesthetics, Intravenous ; blood ; pharmacokinetics ; Animals ; Brain ; metabolism ; Carotid Artery, Internal ; metabolism ; Dogs ; Jugular Veins ; metabolism ; Male ; Propofol ; blood ; pharmacokinetics ; Thalamus ; metabolism

BACKGROUND: To investigate the effects of topiramate (TPM) or lamotrigine (LTG) on cerebral glucose metabolism, we performed 18F-fluorodeoxy glucose positron emission tomography (FDG-PET) before and after medication in patients with drug naive idiopathic generalized epilepsy. METHODS: Thiry-three patients with newly diagnosed as idiopathic generalized epilepsy (IGE) or IGE without antiepileptic drugs after diagnosis were included. Pre- and post-antiepileptic drug FDG-PET were performed (before and after TPM or LTG administration) in 33 subjects treated with TPM or LTG who had been seizure free for at least 8 weeks. Sixteen of patients received TPM (M/F=8/8, aged 29.2+/-12.3 years) and 17 LTG (M/F=8/9, 26.8+/-9.3 years). For statistical paramateric (SPM) analysis, all PET images were spatially normalized to the standard PET template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- and post-medication FDG-PET images. RESULTS: SPM analysis of post- and pre-medication FDG-PETs showed TPM reduced glucose metabolism markedly in the thalamus, corpus callosum, and white matters, whereas LTG decreased glucose metabolism in cortico-striato-entorhinal areas with a false discovery rate corrected p<0.05. No brain region showed post-medication hypermetabolism in either group. CONCLUSION: Our study demonstrates that both TPM and LTG affect the cerebral glucose metabolism in drug naive idiopathic generalized epilepsy patients.
Anticonvulsants ; Brain ; Corpus Callosum ; Diagnosis ; Epilepsy ; Epilepsy, Generalized* ; Glucose* ; Humans ; Immunoglobulin E ; Metabolism* ; Positron-Emission Tomography ; Seizures ; Thalamus

Studies of brain magnetic resonance imaging (MRI) of neonatal white matter damage are few, and descriptions of this type of brain damage are limited. During the past three years, we have encountered three full-term infants with selective white matter damage over the course of their viral illness. All three neonates presented with seizures a few days after showing symptoms of a viral illness. The results of bacterial cultures of the blood, CSF, and stool were negative. Newborn screening tests for organic aciduria, amino acid metabolism disorders, and fatty acid oxidation defects were also negative. In two infants, an electroencephalogram (EEG) showed slow basic activity, which is a typical finding in patients with encephalitis/encephalopathy. The Diffusion-weighted MRI (DWI) showed abnormally high signal intensity localized to the white matter of the corpus callosum, thalamus, internal capsule, or hippocampus. The findings of DWI suggested that the neonates' lesions had occurred recently. All patients recovered completely.
Brain ; Corpus Callosum ; Electroencephalography ; Hippocampus ; Humans ; Infant ; Infant, Newborn* ; Internal Capsule ; Magnetic Resonance Imaging ; Mass Screening ; Metabolism ; Seizures ; Thalamus

BACKGROUND: The purpose of this study was to investigate the differences of cerebral glucose metabolism between narcoleptic patients and normal controls. METHODS: We enrolled 24 patients with narcolepsy who underwent night polysomnography and multiple sleep latency tests to confirm the narcolepsy. 18F-fluorodeoxy glucose positron emission tomography scan was performed in all narcoleptic patients and 24 normal age-sex matched controls. To compare the cerebral glucose metabolism between the two groups, statistical parametric mapping (SPM99) was used. RESULTS: Patients with narcolepsy showed significant decreases of cerebral glucose metabolism in the bilateral rectal and subcallosal gyri, right superior frontal gyrus, right medial frontal gyrus, bilateral precuneus, right inferior parietal lobule, and left supramarginal gyrus of the parietal lobe at the uncorrected P<0.001. The bilateral posterior hypothalami and mediodorsal thalamic nuclei showed glucose hypometabolism at the level of corrected P<0.05 with small volume correction. CONCLUSIONS: This study showed cerebral glucose hypometabolism of hypothalamus-thalamus-orbitofrontal pathways in narcoleptic brains. The distribution of abnormal glucose metabolism is concordant to the cerebral pathways of the hypocretin system.
Brain ; Glucose* ; Humans ; Hypothalamus ; Metabolism* ; Narcolepsy* ; Parietal Lobe ; Polysomnography ; Positron-Emission Tomography ; Rabeprazole ; Thalamic Nuclei ; Thalamus ; Orexins

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
Animals ; Mice ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics* ; Neuralgia ; RNA, Small Interfering ; Thalamus/metabolism* ; Up-Regulation

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

OBJECTIVE: To determine, using proton magnetic resonance spectroscopy (1H MRS) whether thalamotomy in patients with Parkinson's disease gives rise to significant changes in regional brain metabolism. MATERIALS AND METHODS: Fifteen patients each underwent stereotactic thalamotomy for the control of medically refractory parkinsonian tremor. Single-voxel 1H MRS was performed on a 1.5T unit using a STEAM sequence (TR/TM/TE, 2000/14/20 msec), and spectra were obtained from substantia nigra, thalamus and putamen areas, with volumes of interest of 7-8ml, before and after thalamotomy. NAA/Cho, NAA/Cr and Cho/Cr metabolite ratios were calculated from relative peak area measurements, and any changes were recorded and assessed. RESULTS: In the substantia nigra and thalamus, NAA/Cho ratios were generally low. In the substantia nigra of 80% of patients (12/15) who showed clinical improvement, decreased NAA/Cho ratios were observed in selected voxels after thalamic surgery (p < 0.05). In the thalamus of 67% of such patients (10/15), significant decreases were also noted (p < 0.05). CONCLUSION: Our results suggest that the NAA/Cho ratio may be a valuable criterion for the evaluation of Parkinson's disease patients who show clinical improvement following surgery. By highlighting variations in this ratio, 1H MRS may help lead to a better understanding of the pathophysiologic processes occurring in those with Parkinson's disease.
Adult ; Aged ; Aspartic Acid/*analogs & derivatives/metabolism ; Brain/*metabolism/pathology ; Choline/metabolism ; Female ; Human ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Middle Age ; Parkinson Disease/*metabolism/pathology/*surgery ; Protons ; Putamen/metabolism/pathology ; Substantia Nigra/metabolism/pathology ; Thalamus/*metabolism/pathology/*surgery

OBJECTIVE: To examine the differential expression of protein of thalamus in rats with diffuse axonal injury. METHODS: Twenty-five rats were randomly divided into a normal group (n=10) and a trauma group (n=15). Total proteins of brain trauma tissue and normal brain tissue were extracted separately, and then proteins were separated by two dimensional gel electrophoresis and stained with Coomassie brilliant blue. The differentially expressed protein spots were identified with biospectrometry. Images were analyzed by PDQuest 7.0. RESULTS: The distribution of protein spots in the trauma group was similar to that of the normal group, the matching rate was 95%, and the repeatability was good. Proteins were mainly displayed at pI 3-8, with relative molecular mass 14.4-75.0 kD. Compared with the normal group, 16 spots of proteins increased and 18 spots of proteins decreased in the trauma group. CONCLUSION There is some difference in protein expression between the normal group and the trauma group. Brain trauma may lead to changes of proteins in the thalamus.
Animals ; Diffuse Axonal Injury ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Male ; Proteome ; analysis ; Proteomics ; methods ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thalamus ; metabolism

OBJECTIVETo investigate the expressions of gamma aminobutyric acid transporter 1 (GAT-1) and glutamate decarboxylase 65 (GAD65) mRNA in different brain regions at brain propofol uptake equilibrium in dogs.

METHODSEighteen 12- to 18-month-old healthy hybrid dogs were randomized equally into control group (group C), low dose group (group L), and high dose group (group H). In groups L and H, anesthesia was administered by intravenous injection of 5.5 and 7.0 mg/kg propofol followed by propofol infusion at a constant rate of 55 and 70 mg·kg(-1)·h(-1) for 50 min, respectively. Blood samples were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations, and the brain tissues of the hypothalamus, sub thalamus, dorsal thalamus, hippocampus, pons, parietal lobe and frontal lobe were examined for GAT-1 and GAD65 mRNA expressions using quantitative real-time PCR.

RESULTSIn groups L and H, propofol infusion at a constant rate for 50 min resulted in comparable plasma propofol concentrations between the internal carotid artery and jugular vein (P>0.05), but the concentrations differed significantly between the two groups (P<0.01). GAT-1 mRNA levels in the hypothalamus and hippocampus were significantly higher in groups L and H than in group C (P<0.05 and P<0.01), but comparable between the former two groups. The variations of GAT-1 mRNA levels between the hypothalamus and hippocampus were similar in both group L [(61.26∓7.17)% and (79.34∓39.95)%, P>0.05] and group H [(74.64∓19.63)% and (97.12∓32.31)%, P>0.05]. GAT-1 mRNA levels in other brain regions showed no significant difference among the 3 groups. GAD65 mRNA levels were similar between group L and group H, but both significantly higher than that in group C (P<0.01). GAD65 mRNA in other brain regions had no significant difference among the 3 groups.

CONCLUSIONGAT-1 mRNA in the hypothalamus and hippocampus and GAD65 mRNA in the dorsal thalamus are upregulated when propofol uptake reaches an equilibrium in the brain of dogs.

Animals ; Brain ; drug effects ; metabolism ; Dogs ; GABA Plasma Membrane Transport Proteins ; genetics ; metabolism ; Glutamate Decarboxylase ; genetics ; metabolism ; Hippocampus ; drug effects ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Propofol ; pharmacology ; RNA, Messenger ; genetics ; Thalamus ; drug effects ; metabolism

OBJECTIVETo investigate the presence of abnormal metabolism in the thalamus and hypothalamus in patients with first-episode depression.

METHODSThirty drug-naive patients with first-episode depression and 30 age-matched controls were scanned with proton magnetic resonance spectroscopy ((1)H-MRS) for Naa, Cho, Cr and mI.

RESULTSCompared with the control group, the patients showed significantly reduced mI and mI/Cr of the hypothalamus, reduced mI/Cr of the left thalamus, and lowered Cho, ml, and ml/Cr of the right thalamus (P<0.05).

CONCLUSIONPatients with first-episode depression may have myo-inositol and phosphoric acid metabolism disorder in the thalamus and hypothalamus with malfunction of cellular osmotic pressure adjustment mechanism. Abnormal mI/Cr in the thalamus and hypothalamus may represent an important biochemical change in advanced patients with depression.

Adolescent ; Adult ; Case-Control Studies ; Choline ; metabolism ; Creatine ; metabolism ; Depression ; diagnosis ; Female ; Humans ; Hypothalamus ; metabolism ; Inositol ; metabolism ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Protons ; Thalamus ; metabolism ; Young Adult