Biomedical subjects

Gang Zhu

Publications and source records attributed to Gang Zhu.

25 records · Page 2Linked to original sources

PubMed2004

Dural arteriovenous fistulae after forehead knife-cut injury.

Dural arteriovenous fistulae (DAVF) is a rare intracranial vascular disease. It is pathologically characterized by direct shunting of the intracranial artery and vein, which results in cerebral ischemia, intracranial hemorrhage, neural deficit and intracranial murmur. The etiological mechanism of DAVF is not well known, but most researchers think it is associated with congenital abnormal development, especially abnormal development of dural blood vessels at the stage of embryogenesis. Recently, some researchers have found that DAVF is also associated with some acquired factors. This article reports a case who developed DAVF within 2 years after debridement of frontal bone fragmentation, depressed fracture, left frontal lobe contusion and superior sagittal sinus injury due to forehead knife-cut injury. The pathogenic mechanism was explored through a review of the related literatures.

Adult↗

PubMed2004

[Methodological consideration in studying the exocytosis mechanisms using microdialysis].

Microdialysis has become an effective and frequently used technique to study the extracellular levels of monoamine, i.e. dopamine, serotonin and norepinephrine in the central nervous system. However, the detailed exocytosis mechanisms of monoamine using microdialysis has remained to be clarified. The present report introduces methods for administration of voltage-sensitive calcium channel (VSCC) inhibitors and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) inhibitors to clarify the mechanisms of monoamine exocytosis using in vivo microdialysis. The N-type and P-type VSCCs are inhibited by perfusion with omega-conotoxin GVIA and omega-agatoxin IVA, respectively; however, their diffusion rate from internal to external spaces of the microdialysis probe is lower than 1%. Unlike VSCC inhibitors, SNAP-25, synaptobrevin and syntaxin can be cleavaed with botulinum toxin type A, B and C, respectively. These toxins (with molecular weights over 500,000) bind specifically to the presynaptic membrane via the heavy chain, while the light chain enters the cytosol, where it displays zinc-endopeptidase activity directed to proteins of the neuroexocytosis apparatus. Therefore, to prevent SNARE activity, botulinum toxins are microinjected. These two methods, perfusion with VSCC inhibitors and microinjection with botulinum toxins, can contribute to the clarification of the mechanisms of monoaminergic exocytosis.

Animals↗

PubMed2003

Combination of microdissection and microarray analysis to identify gene expression changes between differentially located tumour cells in breast cancer.

Comparison of gene expression changes between cancer cells at the periphery and in the centre of breast cancers was performed using a combination of microdissection and microarray analysis. Cancer cells from the two areas were pooled separately from five patients with ductal carcinoma in situ and separately from five patients with frankly invasive cancer. Limited total RNA, 100-200 ng, from this microdissected tissue required use of the Atlas SMART trade mark Probe Amplification Kit to synthesize and amplify cDNA and make (33)P-labelled probes. Probes were then hybridized to Atlas Human Cancer 1.2 Arrays containing 1176 known genes. Triplicate analysis revealed that 22 genes changed their expression levels in the periphery relative to the central region: 15 upregulated and seven downregulated (arbitrary threshold of 1.5-fold or greater). Differences in RNA levels were confirmed by quantitative real-time PCR for two of the genes and by changes in protein levels, detected by immunohistochemistry, for a couple of representative gene products. Thus, changes in gene expression associated with variation in microanatomical location of neoplastic cells can be detected within even small developing tumour masses.

Adenocarcinoma↗

PubMed2003

Age-dependent modulation of hippocampal excitability by KCNQ-channels.

Recently, mutations of KCNQ2 or KCNQ3, members of the KCNQ-related K(+)-channel (KCNQ-channel) family, were identified as cause of benign familial neonatal convulsions (BFNC). However, the exact pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC remain to be elucidated. To clarify the age-dependent etiology of BFNC, we determined age-dependent functional switching of KCNQ-channels, GABAergic- and glutamatergic-transmission in rat hippocampus. The effects of inhibitors of KCNQ-channel, GABA- and glutamate-receptors on propagation of neuronal-excitability and neurotransmitter release were determined by 64-channel multielectrode-dish (MED64), whole-cell recording, in vitro release technique and in vivo microdialysis biosensor, using rat hippocampus from day of birth (P0) to postnatal-day 56 (P56). Inhibition of KCNQ-channels enhanced depolarization-induced glutamate and GABA releases during P0-P7, but not during P14-P28. Inhibition of KCNQ-channels magnified neuronal-excitability propagation from P0 to P14: maximal at P3, but this effect disappeared by P28. GABA(A)-receptor inhibition surprisingly reduced neuronal-excitability propagation during P0-P3, but not at P7. AMPA/glutamate-receptors inhibition reduced propagation of neuronal-excitability throughout the study period. KCNQ-channels inhibition shortened spike-frequency adaptation, but this stimulation was more predominant during P<7 than P>14. During the first week of life, KCNQ-channels performed as a predominant inhibitory system, whereas after this period GABAergic-transmission switched from excitatory to inhibitory function. Contrary, glutamatergic-transmission has acquired as excitatory function from P0. These findings suggest that the pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC are, at least partially, associated with the interaction between age-dependent reduction of inhibitory KCNQ-channel activity and age-dependent functional switching of the GABAergic-system from excitatory to inhibitory action in neonatal CNS.

Aging↗

PubMed2002

Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel on acetylcholine release in rat frontal cortex.

To clarify the mechanisms of action of antiepileptic drugs (AEDs), carbamazepine (CBZ) and zonisamide (ZNS), on exocytosis mechanisms, the present study determined the concentration-dependent action of CBZ and ZNS, as well as the interaction between these AEDs and voltage-sensitive Ca(2+) channel (VSCC) activity on basal, Ca(2+)- and K(+)-evoked acetylcholine (ACh) release in frontal cortex of freely moving rat using in vivo microdialysis. Perfusion with therapeutic-relevant concentrations of CBZ and ZNS increased basal ACh release, which was regulated by N-type VSCC predominantly and P-type VSCC weakly, whereas supratherapeutic-relevant concentrations of these AEDs reduced this release. The 3.4 mM Ca(2+)-evoked release, which was regulated by N-type VSCC selectively, but not by P-type VSCC, was increased by therapeutic-relevant concentrations of CBZ and ZNS, whereas this release was reduced by supratherapeutic-relevant concentrations of them. The 50 mM K(+)-evoked release, which was regulated by P-type VSCC predominantly and N-type VSCC weakly, was decreased by CBZ and ZNS, in a concentration-dependent manner. These findings indicate that the interplay between enhancement of basal ACh release and reduction of depolarization-related ACh release in the frontal cortex are at least partially involved in a common mechanism of antiepileptic action between CBZ and ZNS.

Acetylcholine↗

PubMed2002

Impaired M-current and neuronal excitability.

PURPOSE: Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ-related K+-channel (KCNQ-channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ-related M- current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability. METHODS: To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64-channel multielectrode dish (MED64) system for novel two-dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP). RESULTS: Dup996, a selective KCNQ-channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The gamma-aminobutyric acid (GABA)A-receptor antagonist, bicuculline, enhanced their propagation, whereas alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/glutamate-receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABAA-receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX. CONCLUSIONS: These results suggest that the occurrence of BFNC cannot be produced by KCNQ-channel dysfunction alone but by reciprocal action between impaired KCNQ channel and the other unknown.

Age Factors↗

PubMed2002

[Mechanisms of interaction between adenosine receptor subtypes on hippocampal serotonin release].

To clarify the mechanisms of interaction between adenosine receptor subtypes (A1R and A2R) on 5-HT release, the present study determined the effects of adenosine receptor subtypes on voltage-sensitive Ca(2+)-channels (VSCCs), protein-kinases (PKs) and synaptic-proteins (SNAREs) related 5-HT release using microdialysis in freely moving rat. A1R-antagonists increased basal 5-HT release, which was reduced by inhibitors of N-VSCC, PKC and syntaxin predominantly, and by inhibitors of PKA and synaptobrevin weakly, but was not affected by P-VSCC inhibitor. In the presence of A1R-antagonist, A2R-agonists increased basal 5-HT release, whose action was inhibited by P-VSCC, PKA and synaptobrevin inhibitors predominantly and reduced by N-VSCC, PKC and syntaxin inhibitors weakly. Under the condition of adenylate-cyclase activation in the absence of A1R-antagonists, A2R-agonists increased basal 5-HT release. K(+)-evoked 5-HT release was enhanced by A1R-antagonist and A2R-agonist, whose actions were inhibited by P-VSCC, PKA and synaptobrevin inhibitors predominantly. These results suggest that an activation of A1R suppresses 5-HT release via an inhibition of N-VSCC/PKC/syntaxin and P-VSCC/PKA/synaptobrevin, and an activation of A2-R stimulates 5-HT release via an enhancement of P-VSCC/PKA/synaptobrevin. Therefore PKA activity plays an important role in the interaction between A1R and A2R on hippocampal 5-HT release.

Animals↗