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Dihydrokainic acid

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Dihydrokainic acid is a chemical compound used in laboratory research. It is a derivative of kainic acid, a natural compound found in certain marine algae. Dihydrokainic acid is primarily used as a tool for studying the function and distribution of glutamate receptors in the central nervous system.

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2 protocols using dihydrokainic acid

1

Neuroprotective Interventions in Hippocampal Injury

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For pharmacologic interventions, the specific GLT-1 inhibitor dihydrokainic acid (DHK, 2 nmol and 4 nmol, respectively; Tocris Bioscience, USA and Canada, 200 μmol/L in 0.01 M PBS; John et al., 2015 (link); Zhang M. et al., 2007 (link)), Gap26 (a connexin mimetic peptide, 10 μL and 20 μL, respectively; BIOPIKE, 300 μmol/L in 0.01 M PBS; Sun et al., 2012 (link)), or the vehicle (25% dimethylsulfoxide (DMSO) in PBS) was injected intracerebroventricularly at 30 min before HPC (ICV, Bregma:1.5 mm lateral, 0.8 mm posterior, 4.0 mm deep). L-methionine-DL-sulfoximine (methionine sulfoximine (MSO), GS inhibitor, Sigma Aldrich, St. Louis, MO, USA; Trabelsi et al., 2017 (link)) was dissolved in 0.9% normal saline and administered intraperitoneally in a dose of 170 mg/kg at 2 h before HPC. Sham animals were injected only with normal saline. A selective Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo (3, 4-d) pyrimidine (PP2, 10 μL and 20 μL, repectively; EMD Chemicals, Inc. San Diego, USA and Canada, 3 mg/L in 100% DMSO; Lennmyr et al., 2004 (link); Hou et al., 2007 (link)), or the vehicle (25% DMSO in PBS) was administered at 24 h before tGCI. To evaluate the cytotoxicity of abovementioned inhibitors to CA1, DHK, Gap26 and PP2 were injected intracerebroventricularly and MSO injected intraperitoneally to Sham animals.
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2

Isoflurane-Induced Neuronal Cell Death in Co-Cultures

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Primary neuronal and mixed neuronal-astrocyte co-cultures at neuronal DIV 7 were exposed for 1 hr to either 2% isoflurane (assessed with a Datex 245 Airway Gas Monitor, Datex Corp., North Clearwater, Fl, USA) in pre-mixed carrier gas (5% C02, 21% O2, balance N2), or to carrier gas alone. Gas flow was maintained at a rate of 2 L/min in a sealed, humidified incubator at 37°C. Neurons were assessed for cell death 24 hrs following isoflurane exposure. In additional experiments, isoflurane-induced neuronal cell death was assessed in primary neuronal cultures following application of conditioned medium from neuronal-astrocyte co-cultures, in co-cultures following astrocyte-targeted knockdown of p75NTR, and in co-cultures with and without the astrocyte-glutamate transporter inhibitor dihydrokainic acid (Tocris Bioscience, Bristol, UK). Finally, neuronal cell death was assessed in neuronal, astrocyte and neuronal-astrocyte co-cultures 24 hrs following application of recombinant proBDNF (1–100 pg/ml, R+D Systems, Minneapolis, MN, USA) plus protease inhibitor (diluted to 1X, G-Biosciences, St. Louis, MO), with and without the p75NTR inhibitor trans-activating transcriptional activator peptide 5 (TAT-Pep5, 10 μM, EMD Millipore, Billerica, MA).
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