Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrauterine infection produces an inflammatory response in the fetus characterized by increased inflammatory cytokines in the fetal brain and activation of brain microglial cells. Intrauterine infection can release bacterial cell wall products into the fetal circulation. Lipopolysaccharides (LPS) are derived from the cell walls of gram negative organisms. The degree of microglial cell activation may influence the extent of brain injury following an inflammatory stimulus. Chemokines, which are released by activated microglia, regulate the influx of inflammatory cells to the brain. Accordingly, therapeutic strategies that reduce the extent of chemokine expression in microglial cells may prove neuroprotective. Minocycline (MN), a semisynthetic tetracycline derivative, protects brain against global and focal ischemia in rodents and inhibits microglial cell activation. To determine if minocycline can reduce the production of chemokines and chemokine receptors in response to LPS, microglial-like BV-2 and HAPI cells were cultured in the presence or absence of 100 ng/ml of LPS. Enzyme-linked immunosorbent assay (ELISA) and semi-quantitative RT-PCR were used to examine changes in inflammatory chemokines (macrophage inflammatory protein-1 (MIP-1alpha), regulated upon activation, normal T cell expressed and secreted (RANTES), and inducible protein-10 (IP-10)) and chemokine receptor (C-C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 3 (CXCR3)) production, respectively. We found that in both cell lines chemokine release after 4-, 8-, and 16-h exposure to LPS was significantly higher compared to non-exposed cells for all the chemokines measured, P<0.001. Minocycline inhibited chemokine release of LPS-stimulated BV-2 cells. There was even greater inhibition (up to 50%) of mRNA expression after exposure to LPS (P<0.001). We conclude that endotoxin enhanced the expression of chemokines and chemokine receptors in microglial-like cell lines. Modulation of this expression was achieved with minocycline. Recognition of the mechanisms whereby minocycline exerts its anti-inflammatory effect on microglia may uncover specific targets for pharmacologic intervention.
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PMID:Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. 1502 59

Hypoxic-ischemic (HI) brain injury in the perinatal period causes significant morbidity. Minocycline (MN) is a tetracycline derivative that has reduced brain injury in various animal models of neurodegeneration, including perinatal ischemia. To determine whether MN can modulate the expression of chemokine receptors and interleukin-10 (IL10) in a model of neonatal brain injury, we produced an HI insult to the right cerebral hemisphere (ipsilateral) of the 7-day-old rat (PD7) by right common carotid artery ligation and 2.25 hr of hypoxia in 8% oxygen. MN (45 mg/kg, i.p.) or vehicle (PBS) was injected twice: 2 days and immediately before the HI insult. At 0, 1, 3, and 24 hr and 14 days after HI, total RNA from the ipsilateral and contralateral (exposed to hypoxia only) hemispheres was extracted, reverse transcribed, and amplified with gene-specific primers using a semiquantitative RT-PCR for macrophage inflammatory protein-1alpha), interferon-inducible protein (IP-10), C-C chemokine receptor 5 (CCR5; MIP-1alpha receptor), C-X-C chemokine receptor 3 (CXCR3; IP-10 receptor), and IL10. We found that, in the ipsilateral hemisphere, a significant (P < 0.05) increase in MIP-1alpha, IP-10, CCR5, and CXCR3 mRNA levels was observed. MN treatment decreased mRNA levels for CCR5 and CXCR3. In contrast, the levels of antiinflammatory cytokine IL10 were markedly decreased as a result of HI insult. Treatment with MN, however, had no effect on IL10. We conclude that MN decreased proinflammatory chemokine receptor expression but had little or no influence on the expression of antiinflammatory cytokine IL10. These effects confirm the antiinflammatory effect of MN in neonatal HI brain injury.
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PMID:Minocycline modulates chemokine receptors but not interleukin-10 mRNA expression in hypoxic-ischemic neonatal rat brain. 1754 54

A strong therapeutic target of ischemic stroke is controlling brain inflammation. Recent studies have implicated the critical role of C-C chemokine receptor 5 (CCR5) in neuroinflammation during ischemic stroke. It has been reported that the expression of the matrix metalloproteinases, MMP-3, MMP-12, and MMP-13, is controlled by CCR5; however, their expressional regulation in the infarct brain has not been clearly understood. This study investigated the mRNA expression of Mmp-3, -12, and -13 in the ischemic cerebral cortex of photothrombosis mouse model. The three Mmps were highly upregulated in the early stages of ischemic stroke and were expressed in different types of cells. Mmp-3 and Mmp-13 were expressed in blood vessel endothelial cells after ischemia-induction, whereas Mmp-12 was expressed in activated microglia. The expression of Mmp-13 in resting microglia and in neurons of uninjured cerebral cortex was lost in the infarct region. Therefore, the MMPs responding to CCR5 are differentially regulated during ischemic stroke.
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PMID:Induced mRNA expression of matrix metalloproteinases Mmp-3, Mmp-12, and Mmp-13 in the infarct cerebral cortex of photothrombosis model mice. 3298 31