Hypoxia/reoxygenation induces cell injury via different mechanisms in cultured rat cortical neurons and glial cells.
Hypoxia/reoxygenation (H/R) causes cell injury/death. We examined the protection by drugs intervening at various stages of the injury cascade in cultured neurons and glia. Primary cultures of rat cortical neurons and mixed glia were subjected to H/R. Measurements of cell death (by lactate dehydrogenase release into the medium) and viability (by MTT reduction) indicated that H/R led to time-dependent injury in both neuronal and mixed glial cultures. The extent of cell injury in neurons was significantly greater than in glia cells. Pretreatment with (+)-MK-801 hydrogen maleate (MK-801) (an N-methyl-D-aspartate antagonist), N(omega)-nitro-L-arginine methyl ester (L-NAME) (an inhibitor of nitric oxide synthase) or free radical scavengers reduced the extent of the H/R-elicited neuronal damage. MK-801, in contrast, was without effect on glial cells while L-NAME was effective. Our results suggest differential mechanism(s) and susceptibility to injury caused by H/R for neurons and mixed glia.
Wang
Ju-Yu
JY
Department of Basic Medical Science, Hung-Kuang Institute of Technology, Sha-Lu, Taichung, Taiwan. jywang@ndmctsgh.edu.tw
Shum
Andrew Y-C
AY
Wang
Jia-Yi
JY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005609:Free Radicals / Q000633:toxicity; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000975:Antioxidants; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C022616:thiazolyl blue; D019331:NG-Nitroarginine Methyl Ester