Poonlarp Cheepsunthorn

Bio: Poonlarp Cheepsunthorn is an academic researcher from Chulalongkorn University. The author has contributed to research in topics: Microglia & Neuroinflammation. The author has an hindex of 11, co-authored 20 publications receiving 827 citations. Previous affiliations of Poonlarp Cheepsunthorn include AstraZeneca & Pennsylvania State University.

Characterization of a novel brain-derived microglial cell line isolated from neonatal rat brain

Abstract: We observed highly aggressively proliferating immortalized (HAPI) cells growing in cultures that had been enriched for microglia. The cells were initially obtained from mixed glial cultures prepared from 3-day-old rat brains. HAPI cells are typically round with few or no processes when cultured in 10% serum containing medium. As the percentage of serum in the medium is decreased, the HAPI cells have more processes. HAPI cells stain for the isolectin B4, OX-42, and GLUT5, which are markers for microglial cells, but the cells do not immunolabel with A2B5, a marker of cells in the oligodendroglial cell lineage, or with the astrocyte-specific marker, glial fibrillary aciidic protein (GFAP). In addition, HAPI cells are capable of phagocytosis. We conclude that HAPI cells are of microglia/macrophage lineage. Exposing HAPI cells to lipopolysaccharide (LPS) induces the mRNAs for tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS). LPS exposure also induces secretion of TNF-α and production of nitric oxide (NO) in HAPI cells. Because activation of microglia is associated with an increase in iron accumulation and ferritin expression, we tested the hypothesis that iron status affects the production of TNF-α and NO. Our studies demonstrate that both iron chelation and iron loading diminished the LPS-induced effect of TNF-α and NO. The results of this study indicate that HAPI cells possess the characteristics of microglia/brain macrophages, providing an alternative cell culture model for the study of microglia. In addition, we demonstrate that the activation of microglial cells could be modified by iron. GLIA 35:53–62, 2001. © 2001 Wiley-Liss, Inc.

Cellular distribution of ferritin subunits in postnatal rat brain.

Abstract: The normal development of the brain requires finely coordinated events, many of which require iron. Consequently, iron must be available to the brain in a timely manner and in a bioavailable form. However, the brain also requires stringent mechanisms to protect itself from iron-induced oxidative damage. The protein that is best suited to making iron available but also adequately protecting the cell is the intracellular iron storage protein ferritin. Typically, ferritin is composed of 24 subunits of H and L chains, which are functionally distinct. This study was undertaken to determine the expression of ferritin subunits during normal development of the postnatal rat brain. There is a shift in ferritin-containing cell types during development from predominantly microglia at postnatal day 5 (PND 5) to predominantly oligodendrocytes by PND 30. At PND 5, microglia are found throughout gray and white matter areas of the brain, but only amoeboid microglia in discrete foci in the subcortical white matter are ferritin positive. At PND 15, some oligodendrocytes in the subcortical white matter express ferritin, but the majority of ferritin-containing cells within white matter are still microglia. By PND 30, the predominant ferritin-containing cell type within white matter are oligodendrocytes. Generally, the cellular distribution of both ferritin subunits were identical with one major exception; H-ferritin, but not L-ferritin, was present in neuronal nuclei in the cortex. These data suggest that microglia play a role in brain iron homeostasis during normal postnatal development and may influence myelination by competing with oligodendrocytes for iron.

Characterization of putative Japanese encephalitis virus receptor molecules on microglial cells

Abstract: Japanese encephalitis virus (JEV) a mosquito-borne flavivirus is a major cause of viral encephalitis in Asia. While the principle target cells for JEV in the central nervous system are believed to be neurons, microglia are activated in response to JEV and have been proposed to act as a long lasting virus reservoir. Viral attachment to a host cell is the first step of the viral entry process and is a critical mediator of tissue tropism. This study sought to identify molecules associated with JEV entry to microglial cells. Virus overlay protein-binding assay (VOPBA) and liquid chromatography-mass spectrometry (LC/MS/MS) identified the 37/67 kDa high-affinity laminin receptor protein and nucleolin as a potential JEV-binding proteins. These proteins were subsequently investigated for a contribution to JEV entry to mouse microglial BV-2 cells together with other possible candidate receptor molecules including Hsp70, Hsp90, GRP78, CD14, and CD4. In antibody mediated inhibition of infection experiments, both anti-laminin receptor and anti-CD4 antibodies significantly reduced virus entry while anti-Hsp70 and 90 antibodies produced a slight reduction. Significant inhibition of virus entry (up to 80%) was observed in the presence of lipopolysaccharide (LPS) which resulted in a complete down-regulation of CD4 and moderate down-regulation of CD14. These results suggest that multiple receptor proteins may mediate the entry of JEV to microglial cells, with CD4 playing a major role.

Biomedical Applications of Biodegradable Polymers

Abstract: Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. In order to fit functional demand, materials with desired physical, chemical, biological, biomechanical and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications.

Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment.

Abstract: Free radicals and other so-called 'reactive species' are constantly produced in the brain in vivo. Some arise by 'accidents of chemistry', an example of which may be the leakage of electrons from the mitochondrial electron transport chain to generate superoxide radical (O2*-). Others are generated for useful purposes, such as the role of nitric oxide in neurotransmission and the production of O2*- by activated microglia. Because of its high ATP demand, the brain consumes O2 rapidly, and is thus susceptible to interference with mitochondrial function, which can in turn lead to increased O2*- formation. The brain contains multiple antioxidant defences, of which the mitochondrial manganese-containing superoxide dismutase and reduced glutathione seem especially important. Iron is a powerful promoter of free radical damage, able to catalyse generation of highly reactive hydroxyl, alkoxyl and peroxyl radicals from hydrogen peroxide and lipid peroxides, respectively. Although most iron in the brain is stored in ferritin, 'catalytic' iron is readily mobilised from injured brain tissue. Increased levels of oxidative damage to DNA, lipids and proteins have been detected by a range of assays in post-mortem tissues from patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis, and at least some of these changes may occur early in disease progression. The accumulation and precipitation of proteins that occur in these diseases may be aggravated by oxidative damage, and may in turn cause more oxidative damage by interfering with the function of the proteasome. Indeed, it has been shown that proteasomal inhibition increases levels of oxidative damage not only to proteins but also to other biomolecules. Hence, there are many attempts to develop antioxidants that can cross the blood-brain barrier and decrease oxidative damage. Natural antioxidants such as vitamin E (tocopherol), carotenoids and flavonoids do not readily enter the brain in the adult, and the lazaroid antioxidant tirilazad (U-74006F) appears to localise in the blood-brain barrier. Other antioxidants under development include modified spin traps and low molecular mass scavengers of O2*-. One possible source of lead compounds is the use of traditional remedies claimed to improve brain function. Little is known about the impact of dietary antioxidants upon the development and progression of neurodegenerative diseases, especially Alzheimer's disease. Several agents already in therapeutic use might exert some of their effects by antioxidant action, including selegiline (deprenyl), apomorphine and nitecapone.

Glucose-6-phosphate dehydrogenase deficiency.

Abstract: Glucose-6-phosphate dehydrogenase deficiency is a genetic disorder that occurs almost exclusively in males. This condition mainly affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. In affected individuals, a defect in an enzyme called glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely. This destruction of red blood cells is called hemolysis.