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Minocycline modulates chemokine receptors but not interleukin‐10 mRNA expression in hypoxic‐ischemic neonatal rat brain
Author(s) -
Kremlev Sergey G.,
Roberts Rebecca L.,
Palmer Charles
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21380
Subject(s) - chemokine , receptor , interleukin 10 , medicine , cxcr3 , chemokine receptor , endocrinology , biology , cytokine
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‐1α), interferon‐inducible protein (IP‐10), C‐C chemokine receptor 5 (CCR5; MIP‐1α 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‐1α, 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. © 2007 Wiley‐Liss, Inc.