Minocycline Prevent Microglial Activation via Suppression of Adenosine A 2A Receptor in a Rat Stroke Ischemia/Reperfusion Model

TAO Tao, FU Jie, LIU Yong-gang. et al

Abstract

To investigate whether minocycline could inhibit neuroinflammation induced by microglia activation through suppression of adenosine A2Areceptor (A2AR)expression in rats after cerebral ischemia/reperfusion (I/R) injury. Methods Thirty male Sprageue-Dawley rats were randomly divided into 3 groups: sham group, I/R group and minocycline group. The rats were subjected to occlusion of the right middle cerebral artery (MCAO) for 2 h to establish stroke I/R model, and 3 mg/kg minocycline was injected intravenously immediately after reperfusion twice a day in minocycline group. At 24 h after I/R, the inflammatory cytokines IL-1β and IL-6 in peri-infarct region were measured by Western blot, microglia activation was detected by double-immunofluorescence labeling. A2AR density was detected by immunohistofluorescence and Western blot. Results The number of CD11b-positive cells in I/R group was increased when compared with that in sham group. The expressions of IL-1β, IL-6 and A2AR were markedly up-regulated after I/R. Minocycline significantly decreased the expressions of IL-1β, IL-6 and A2AR and the number of CD11b-positive cells in peri-infarct region. Conclusion Minocycline could prevent cerebral ischemia induced neuroinflammation by the suppression of microglial activation, which may be related to down-regulation of A2ARexpression.

 

Keywords: Minocycline, Adenosine, A2Areceptor, Cerebral ischemia reperfusion, Microglia 

 

Full Text:

PDF


References


REBOLA N, SIMOES AP, CANAS PM, et al. Adenosine receptors control neuroinflammation and consequent hippocampal neuronal dysfunction. J Neurochem, 2011, 117 (1) : 100-111.

PLANE JM, SHEN Y, PLEASURE DE, et al. Prospects for minocycline neuroprotection. Arch Neurol,2010,67(12); 1442-144.

SHIGEMOTOMOGAMI Y, HOSHIKAWA K, GOLDMAN JE, et al. Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci.2014.34(6):2231-2243.

LARTEY FM, AHN GO, ALI R. et al. The relationship between serial [(18)F]PBR06 PET imaging of microglial activation and motor function following stroke in mice. Mol Imaging Biol,2014 Л6(6): 821 -829.

ZHOU R. YANG Z, TANG X, et al. Propofol protects against focal cerebral ischemia via inhibition of microglia- mediated proinflammatory cytokines in a rat model of experimental stroke. PLoS One, 2013 , 8 ( 12) ; e82729 [2016- 04-21]. http;//dx. doi. org/10. 1371/journal, pone. 0082729.

LENZ KM, NUGENT BM, HAL1YUR R, et al. Microglia are essential to masculinization of brain and behavior. J Neurosci,2013,33(7) :2761-2772.

JIN R, YANG G, LI G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol, 2010,87(5):779-787.

FRANCO ЕС, CARDOSO MM. GOUVEIA A. et al. Modulation of microglial activation enhances neuroprotection and functional recovery derived from bone marrow mononuclear cell transplantation after cortical ischemia. Neurosci Res, 2012,73(2); 122-132.

CAI ZY, YAN Y, CHEN R. Minocycline reduces astrocytic reactis'ation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model. Neurosci Bulb 2010,26(1):28-36.

TRINCAVELLI ML, MELANI A, GUIDI S, et al. Regulation of A,a adenosine receptor expression and functioning following permanent focal ischemia in rat brain. J Neurochem, 2008,104(2);479-490.


Refbacks

  • There are currently no refbacks.