Experimental treatment for focal hyperglycemic ischemic brain injury in the rat.
Hyperglycemia aggravates ischemic brain injury, possibly due to the activation of signaling pathways involving reactive oxygen species, Src and mitogen-activated protein kinases. The aim of this study was to investigate the effects of the spin trap agent alpha-phenyl-N-tert-butyl nitrone (PBN), the Src family kinase inhibitor PP2 and the MEK1-inhibitor U0126 on focal hyperglycemic ischemic brain injury. Temporary middle cerebral artery occlusion (90 min) was induced in four groups of rats (PBN, PP2, and U0126 vs. control). Neurological testing and tetrazolium red staining were performed after 1 day. PBN decreased the infarct volume by 70% compared with the control (P<0.05) and a tendency towards reduced infarcts was seen in the PP2 or U0126 groups. Furthermore, neurological testing was consistent with the volumetric analysis. In conclusion, PBN appears to be a potential neuroprotective agent in hyperglycemic, focal ischemic brain injury, while the efficacy of PP2 and U0126 could not be confirmed by the present data.
Farrokhnia
Nasim
N
Department of Medical Sciences, Stroke Unit, Uppsala University Hospital, Sweden. nasim.farrokhnia@medsci.uu.se
Roos
Magnus W
MW
Terént
Andreas
A
Lennmyr
Fredrik
F
D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002070:Butadienes / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000097:blood; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006943:Hyperglycemia / Q000150:complications* / Q000473:pathology; D008297:Male; D009460:Neurologic Examination / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011743:Pyrimidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013997:Time Factors
C412373:AG 1879; D001786:Blood Glucose; D002070:Butadienes; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D009570:Nitriles; D009589:Nitrogen Oxides; D011743:Pyrimidines; D013778:Tetrazolium Salts; C113580:U 0126; D002245:Carbon Dioxide; C029217:phenyl-N-tert-butylnitrone; D010100:Oxygen