Nitric oxide induces macrophage apoptosis following traumatic brain injury in rats.
This study examined the apoptotic mechanisms of macrophages following a lateral fluid percussive brain injury. A marked induction of inducible NO synthase (iNOS) immunoexpression was observed in brain macrophages in the subarachnoid space and lateral ventricles ipsilateral to the injury. Numerous apoptotic macrophages occurred in the same region 7 days after the injury as shown by in situ terminal transferase d-UTP nick-end labeling (TUNEL) and caspase-3 immunohistochemistry. Double immunofluorescence staining showed that only a small number of TUNEL positive cells were iNOS positive; many TUNEL positive cells, however, were observed in the vicinity of iNOS positive cells. Administration of aminoguanidine resulted in a marked reduction of apoptotic cells in the lesioned area suggesting that overproduction of NO is linked to diminution of brain macrophages by apoptosis.
Lu
Jia
J
Defence Medical Research Institute, Defence Science & Technology Agency, 18 Medical Drive, #01-06, MD2, Singapore 117597, Singapore. nmiv6@nus.edu.sg
Moochhala
Shabbir
S
Shirhan
Md
M
Ng
Kian Chye
KC
Tan
Mui Hong
MH
Teo
Ai Ling
AL
Ling
Eng Ang
EA
D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006146:Guanidines / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010474:Percussion; D051381:Rats; D017207:Rats, Sprague-Dawley
D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine