Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats

Abstract

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.

Aims of the study: We hypothesized that S-PBN might be neuroprotective in hyperglycemic focal cerebral ischemia.

Material and 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.

Conclusion: 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.

Figure 1.

Neurological scoring according to Bederson et al. (16) (ranging from: 0 = normal, 1 = forelimb flexion, 2 = decreased resistance to lateral push, or 3 = circling) indicated a better performance in the S-PBN-treated group than in the control group. *P < 0.05 (Mann-Whitney test) (S-PBN = sodium 2-sulfophenyl-N-tert-butyl nitrone).

Figure 2.

Performance on the inclined plane. The average of the three maximal angles was recorded prior to middle cerebral artery occlusion (MCAO) and after 1 day of survival. The S-PBN group managed better than the controls. Mean ± SD for 6 S-PBN-treated and 7 control rats. *P < 0.05; **P < 0.01 (unpaired t test) (S-PBN = sodium 2-sulfophenyl-N-tert-butyl nitrone).

Figure 3.

Volumetric analyses of the total brain volume and infarct size were carried out in serial 2 mm slices of brain tissue stained by tetrazolium red (TTC). Normal tissue is stained by TTC while the infarcts appear pale.