Expression of inducible nitric oxide synthase and cyclooxygenase-2 after excitotoxic damage to the immature rat brain.
It is well established that after adult brain damage the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play an important role in the inflammatory processes and oxidative stress, which are considered to be the leading factors contributing to delayed cell death. The contribution of these enzymes to postnatal brain damage, however, is poorly understood. In our study, excitotoxic lesions were induced by the injection of N-methyl-D-aspartate in the cortex of postnatal day 9 rats. After different survival times ranging from 4 hr to 7 days post-lesion, brain sections were processed for the immunocytochemical demonstration of COX-2 and iNOS and double labeling with neuronal, glial and neutrophil markers. First and maximal de novo induction of iNOS and COX-2 expression was found at 10 hr post-lesion. Expression of both enzymes started to diminish at 24 hr, reaching basal levels at day 3. iNOS-expressing cells were mainly identified as infiltrated neutrophils as well as highly ramified protoplasmic astrocytes closely associated with blood vessels. Moreover, scattered iNOS-positive neurons were found at the lesion borders. In contrast, COX-2 was mainly observed in reactive microglial cells and neuronal cells. COX-2-positive neurons were found within the degenerating area at 10 hr and at the borders of the lesion later on. This study shows that maximal iNOS and COX-2 expression precedes the period of massive neuronal death observed at 24 hr post-lesion, and may therefore contribute to the evolution of the inflammatory response and the neurodegenerative process after an excitotoxic lesion to the postnatal brain.
Acarin
Laia
L
Unit of Histology, School of Medicine, Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Spain. laia.acarin@uab.es
Peluffo
Hugo
H
González
Berta
B
Castellano
Bernardo
B
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000201:enzymology*; D016923:Cell Death; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D018690:Excitatory Amino Acid Agonists; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D016202:N-Methylaspartate; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052248:Nitric Oxide Synthase Type I; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases