Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats.
BACKGROUND
Hyperglycemia exacerbates focal ischemic brain damage supposedly through various mechanisms. One such mechanism is oxidative stress involving reactive oxygen and nitrogen species (RONS) production. Nitrones attenuate oxidative stress in various models of brain injury. Sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) can be administered experimentally and has been shown to be neuroprotective in experimental brain trauma.


OBJECTIVE
We hypothesized that S-PBN might be neuroprotective in hyperglycemic focal cerebral ischemia.


METHODS
Rats were made hyperglycemic by an intraperitoneal bolus injection of glucose (2 g/kg) and then subjected to 90 min transient middle cerebral artery occlusion (MCAO). They were randomized to a therapeutic regime of S-PBN (156 mg/kg) or saline given intravenously. Neurological testing according to Bederson and tetrazolium red staining were performed after 1 day.


RESULTS
S-PBN improved the neurological performance at day 1 both in Bederson score (1.3+/-0.8 versus 2.7+/-0.48) and on the inclined plane (74.5%+/-4.6 (S-PBN) versus 66%+/-8.3 (control), P<0.05) but did not reduce the infarct size. Physiological data did not differ between groups.


CONCLUSIONS
S-PBN may improve neurological performance at short-term survival (1 day) in the present model of hyperglycemic-ischemic brain injury in rats. This effect appeared not to be primarily related to reduced infarct size.
Molnar
Maria
M
Department of Surgical Sciences, Section of Anesthesiology and Intensive Care, Uppsala University Hospital, Uppsala, Sweden. maria.molnar@akademiska.se
Lennmyr
Fredrik
F
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D006943:Hyperglycemia / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001557:Benzenesulfonates; D018696:Neuroprotective Agents; C094272:N-tert-butyl-(2-sulfophenyl)nitrone