Oxidative stress and glutamate excitotoxicity contribute to apoptosis in cerebral venous sinus thrombosis.
Cerebral venous sinus thrombosis (CVST) is an important cause of stroke in young especially in the developing countries. There is paucity of studies on the mechanism of cell damage in CVST. Aim of this study is to explore the role of glutamate excitotoxicity, oxidative stress; and apoptosis in an experimental model of CVST. Cerebral venous sinus thrombosis was induced by putting a strip of filter paper soaked in 40% ferric chloride on superior sagittal sinus. Brain was removed on day 1, 2 and 7 and oxidative stress markers (Mn-SOD, Catalase, GPx, LPO and GSH) were estimated spectrophotometrically. Glutamate level and its receptors NR1, NR2A and NR2B were estimated by real time polymerase chain reaction. The markers of apoptosis were evaluated by expression of cleaved Caspase-3 and specrtin break down product (SBDP) by western blot. In CVST, the evidence of oxidative stress (reduced activity of Mn-SOD, Catalase, GPx, GSH and increased level of LPO) was noted. Glutamate level was elevated and its receptors NR1, NR2A and NR2B were reduced. Increased expression of cleaved Caspase-3 on day 2 and 7 and SBDP on day 1 and 2 were noted. Oxidative stress, glutamate excitotoxicity and apoptosis seem to have important role in CVST induced cell damage.
Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
Hari Shanker
HS
Tiwari
Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India. Electronic address: drukmisra@rediffmail.com.
Usha Kant
UK
Misra
Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
Jayantee
J
Kalita
Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India.
Akanksha
A
Mishra
Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India.
Shubha
S
Shukla
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012851:Sinus Thrombosis, Intracranial / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism
D002712:Chlorides; D005290:Ferric Compounds; D018698:Glutamic Acid; D013482:Superoxide Dismutase; C024555:ferric chloride
Antioxidant enzymes; Cerebral venous sinus thrombosis; Cleaved caspase −3; Oxidative stress; Specrtin breakdown product; Stroke