Animal experiment:

Rats[2]To investigate the effects of Indomethacin treatment on both microglia activation, neuroprotection and adult neurogenesis, rats are divided in four experimental groups: animals injected with ET-1, treated with sterile saline (i.p.) for 7 days and perfused at 8 days following ET-1 injection (group 1, n=4); animals injected with ET-1, treated with Indomethacin (2.5 mg/kg, i.p) for 7 days and perfused at 8 days following ET-1 injection (group 2, n=4); animals injected with ET-1, treated with sterile saline (i.p.) for 7 days and perfused at 14 days following ET-1 injection (group 3, n=4); animals injected with ET-1, treated with Indomethacin (2.5 mg/kg, i.p) for 7 days and perfused at 14 days following ET-1 injection (group 4, n=4). After survival times of 7 or 14 days, animals are deeply anesthetized with a mixture of ketamine hydrochloride (72 mg/kg, i.p.) and xylazine hydrochloride (9 mg/kg, i.p.). After the verification of complete absence of both the corneal and the paw withdraw reflexes, the animals are transcardially perfused with heparinized 0.9% warm phosphate-buffered saline (PBS) followed by 4% cold paraformaldehyde in 0.1 M phosphate buffer (PB), pH 7.4. Brains are post-fixed for 24 h in the same fixative and cryoprotected in different gradients of sucrose-glycerol solutions over 7 days. The tissue is then frozen in an embedding medium, and cut at 30 μM in the coronal plane using a cryostat. Sections are then mounted onto gelatinized slides and stored in a freezer at –20℃[2].

Indomethacin is a potent and nonselective inhibitor of COX1 and COX2, with IC50s of 18 nM and 26 nM for human COX-1 and COX-2, respectively, in CHO cells.

Indomethacin is a potent and nonselective inhibitor of COX1 and COX2, with IC50s of 18 nM and 26 nM for human COX-1 and COX-2, respectively, in CHO cells. Indomethacin inhibits lipopolysaccharide (LPS)-induced PGE2 production (COX-2) in a human whole blood assay with a potency (IC50=0.68±0.17 μM), and suppresses coagulation-induced TXB2 production (COX-1) (IC50=0.19±0.02 μM). Indomethacin blocks COX-1 with an IC50 of 20±1 nM in U937 cell microsomes at a low arachidonic acid concentration (0.1 μM)[1].

Indomethacin dose-dependently inhibits both the carrageenan-induced rat paw oedema (ED50, 2.0 mg/kg), hyperalgesia (ED50, 1.5 mg/kg), and is also effective at reversing LPS-induced pyrexia in rats (ED50, 1.1 mg/kg)[1]. Indomethacin (2.5 mg/kg, i.p) decreases the number of NeuN+ cells in the animals at 8 days after ET-1 injection. Indomethacin also reduces microglia/macrophage activation at 14 days. Indomethacin significantly increases the number of SVZ DCX+ cells/field at 14 days post stroke[2]. Indomethacin (22.9 mg/kg, p.o.) produces 8 to 10 linear mucosal lesions extended from the fundic to pyloric area of stomach wall[3].

References:
[1]. Riendeau D, et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol. 1997 May;121(1):105-17.
[2]. Lopes RS, et al. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia. J Biosci. 2016 Sep;41(3):381-94.
[3]. Afroz S, et al. Concentrated phosphatidic acid in cereal brans as potential protective agents against indomethacin-induced stomach ulcer. J Agric Food Chem. 2016 Aug 26.
[4]. Qixiong Zhang, et al. Structure-Property Correlations of Reactive Oxygen Species-Responsive and Hydrogen Peroxide-Eliminating Materials with Anti-Oxidant and Anti-Inflammatory Activities. Chem Mater. 2017, 29(19):8221-8238.