Preconditioning with sublethal ischemia or intermittent normobaric hyperoxia up-regulates glutamate transporters and tumor necrosis factor-alpha converting enzyme in the rat brain.
BACKGROUND
Recent studies suggest that sublethal ischemia and intermittent normobaric hyperoxia (InHO) protect the brain from subsequent ischemic injury. In this, changes in the expression of excitatory amino-acid transporters (EAATs) and tumor necrosis factor-alpha converting enzyme (TACE) may play a role. We sought to identify and clarify the nature of any such changes.


METHODS
Rats were divided into 3 experimental groups, each of 15 animals. The first group was exposed to normobaric hyperoxia (fractional inspired oxygen concentration 95%) for 4 hours/day for 6 consecutive days (InHO). The second group acted as controls, and was exposed to 21% oxygen in the same chamber (room air). The third group acted as a model of ischemic preconditioning, and was exposed to 21% oxygen in the same chamber and subjected to 10 minutes of temporary middle cerebral artery (MCA) occlusion (tMCAO). After 24 hours, 9 animals from each group were subjected to 60 minutes of right MCA occlusion (MCAO). After 24 hours of reperfusion, neurologic deficit score and infarct volume were assessed in MCAO-operated subgroups. The remaining 6 animals in each group remained intact and, 48 hours after pretreatment, were killed for assessment of EAATs and TACE expression in the ipsilateral hemisphere.


RESULTS
Preconditioning with InHO and tMCAO decreased neurologic deficit score and infarct volume, and increased expression of EAAT1, EAAT2, EAAT3, and TACE.


CONCLUSIONS
InHO and tMCAO are associated with expression of EAAT1, EAAT2, EAAT3, and TACE, consistent with an active role in the genesis of ischemic protection.
Bigdeli
Mohammad Reza
MR
Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran. bigdelimohammadreza@yahoo.com
Rahnema
Mehdi
M
Khoshbaten
Ali
A
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D001274:Atmospheric Pressure; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat