Biomedical subjects

Hung-Dong Joh

Publications and source records attributed to Hung-Dong Joh.

3 recordsLinked to original sources

PubMed2006

Estradiol alters only GAD67 mRNA levels in ischemic rat brain with no consequent effects on GABA.

The present study tested the hypothesis that estradiol reduces tissue infarction after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by augmenting glutamic acid decarboxylase (GAD) expression and thus activity, leading to increases in gamma-amino-butyric acid (GABA) tissue levels. Glutamic acid decarboxylase is the principal enzyme for GABA synthesis and has two isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25 microg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic cohorts. Selected cortical and striatal regions were microdissected from harvested brains. GAD65/67 mRNA levels were determined by microlysate ribonuclease protection assay. End-ischemic GABA concentrations were determined by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA levels. In most brain regions evaluated, regional GABA concentrations increased with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases in GABA concentration only in dorsomedial cortex. These data suggest that estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels but does not alter steady-state GABA concentrations. It may be that estradiol under ischemic conditions is attenuating GABA metabolism rather than enhancing synthesis or is augmenting other aspects of GABAergic transmission such as GABA transporters and receptors.

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PubMed2002

Postischemic angiogenic factor expression in stroke-prone rats.

Spontaneously hypertensive stroke-prone rats (SHRSP), a model for genetic stroke susceptibility, suffer spontaneous stroke and enhanced injury after experimental stroke, in part due to abnormal cerebrovascular development. We hypothesized that angiopoietin system genes in SHRSP may follow unique patterns of expression after experimentally induced stroke. SHRSP, hypertensive control rats (SHR), and normotensive controls (WKY) were subjected to experimental middle cerebral artery occlusion, and brain RNA was analyzed for expression of angiogenic genes. Expression of angiopoietin-2 increased after stroke in all rat strains and was significantly enhanced in SHRSP compared with control strains. In addition, expression of angiopoietin-1 and the angiopoietin receptor dropped markedly after stroke in SHRSP animals, but was not different after ischemia in SHR and WKY strains. Thus, the SHRSP brain elaborates a unique and specific pattern of angiopoietin system gene expression after stroke which may underlie stroke susceptibility of these rats.

Angiogenesis Inducing Agents↗

PubMed2002

Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) is a risk factor for stroke. However, TIA may also serve as a preconditioning stimulus, reducing damage from subsequent stroke. We tested the hypothesis that experimental TIA induces expression of P450 2C11, an arachidonic acid epoxygenase that produces vasodilator epoxyeicosatrienoic acids, leading to increased tissue perfusion and reduced stroke damage. METHODS: Wistar rats underwent three 10-minute middle cerebral artery occlusions (TIA) or sham surgery. Three days later, animals were subjected to 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. Brains were stained with 2,3,5-triphenyltetrazolium chloride for infarct size measurement or processed for quantification of P450 2C11 mRNA and protein with the use of RNase protection assay and Western blotting. Regional cerebral blood flow (CBF) at the end of 2-hour ischemia was measured in separate groups of rats with iodoantipyrine autoradiography. RESULTS: Cerebral infarct was reduced by >50% in TIA- versus sham-preconditioned animals. 2C11 mRNA and protein were increased in ipsilateral hemisphere by 3 days after TIA but not sham surgery. Induction of 2C11 by TIA was also evident in ipsilateral hemisphere at 24 hours after 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. End-ischemic regional CBF was not different between TIA- and sham-pretreated groups. CONCLUSIONS: We conclude that experimental TIA induces ischemic tolerance by a mechanism temporally linked to upregulation of P450 2C11. Enzyme induction does not attenuate ischemic severity by amplifying end-ischemic CBF.

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