Cortical spreading depression induces the expression of iNOS, HIF-1alpha, and LDH-A.
The mechanisms of tolerance to subsequent episodes of ischemia induced by cortical spreading depression (CSD) are not clear. The effects of CSD on the expression of inducible nitric oxide synthase (iNOS), hypoxia inducible factor-1alpha (HIF-1alpha), and lactate dehydrogenase-A (LDH-A) were evaluated in the present experiment. Unilateral CSD was induced in Sprague-Dawley rats by application of KCl on the right cortex and the mRNA levels of iNOS, HIF-1alpha, and LDH-A were evaluated at 15 min, 2 h, 4 h, 6 h or 24 h after CSD. RT-PCR analysis showed: 1) an increase of iNOS mRNA at 15 min, 2 h, 4 h; 2) an increase of HIF-1alpha mRNA at 6 h; 3) an increase of LDH-A mRNA at 4 h. In situ hybridization with specific digoxigenin-labeled oligonucleotides revealed that the mRNA levels were increased at 15 min-2 h for iNOS, 2-4 h for LDH-A and 6 h for HIF-1 after CSD. Immunohistochemistry analysis revealed that levels of iNOS and HIF-1alpha were increased, respectively, at 2 h and 6 h after CSD. These data suggest that CSD promotes the expression of iNOS, HIF-1alpha, and LDH-A in nervous cells giving a neuroprotective effect.
Viggiano
E
E
Department of Experimental Medicine, Section of Human Physiology, Second University of Naples, Via Costantinopoli 16, 80138 Napoli, Italy. emanuela.viggiano@unina2.it
Ferrara
D
D
Izzo
G
G
Viggiano
A
A
Minucci
S
S
Monda
M
M
De Luca
B
B
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000502:physiology*; D019610:Cytoprotection / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008297:Male; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D012333:RNA, Messenger; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat