NDLI: SCH58261 the Selective Adenosine A$_{2A}$ Receptor Blocker Modulates Ischemia Reperfusion Injury Following Bilateral Carotid Occlusion: Role of Inflammatory Mediators

Content Provider	Springer Nature Link
Author	Mohamed, R. A. Agha, A. M. Nassar, N. N.
Copyright Year	2011
Abstract	In the present study, the effects of SCH58261, a selective adenosine A$_{2A}$ receptor antagonist that crosses the blood brain barrier (BBB) and 8-(4-sulfophenyl) theophylline (8-SPT), a non-selective adenosine receptor antagonist that acts peripherally, were investigated on cerebral ischemia reperfusion injury (IR). Male Wistar rats (200 - 250 g) were divided into four groups: (1) sham-operated (SO), IR pretreated with either (2) vehicle (DMSO); (3) SCH58261 (0.01 mg/kg); (4) 8-SPT (2.5 mg/kg). Animals were anesthetized and submitted to occlusion of both carotid arteries for 45 min. All treatments were administered intraperitoneally (i.p.) post carotid occlusion prior to exposure to a 24 h reperfusion period. Ischemic rats showed increased infarct size compared to their control counterparts that corroborated with histopathological changes as well as increased lactate dehydrogenase (LDH) activity in the hippocampus. Moreover, ischemic animals showed habituation deficit, increased anxiety and locomotor activity. IR increased hippocampal glutamate (Glu), GABA, glycine (Gly) and aspartate (ASP). SCH58261 significantly reversed these effects while 8-SPT elicited minimal change. IR raised myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), prostaglandin E$_{2}$ (PGE$_{2}$) accompanied by a decrease in interleukin-10 (IL-10), effects that were again reversed by SCH58261, but 8-SPT elicited less changes. Results from the present study point towards the importance of central blockade of adenosine A$_{2A}$ receptor in ameliorating hippocampal damage following IR injury by halting inflammatory cascades as well as modulating excitotoxicity.
Starting Page	538
Ending Page	547
Page Count	10
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	37
Issue Number	3
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2011-11-10
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Adenosine Ischemia reperfusion injury Hippocampus Neurotransmitters NO TNF-α Neurology Cell Biology Neurochemistry Neurosciences Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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