Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion.

Abstract

The methionine analogue methionine sulfoximine was administered to 10 rats 24 hours before occlusion of the proximal left middle cerebral artery. Three days later the rats were decapitated and the brain infarct volumes were compared with those in 10 control rats that received saline before middle cerebral artery occlusion. The mean volume of the infarct in the cerebral cortex was reduced by 33% in the group treated with methionine sulfoximine (/?<0.01). This protective effect may be mediated by a presynaptic mechanism; methionine sulfoximine profoundly inhibits brain glutamine synthetase, thereby interrupting the astrocyte-neuron glutamate shuttle and impairing neuronal glutamate release. Methionine sulfoximine also increases brain glycogen stores, and this increased energy reserve may benefit penumbral tissue during the peri-infarct period. Further study of the mechanisms by which methionine sulfoximine decreases infarct volume could lead to new therapeutic approaches for stroke. (Stroke 1990;21:322-327)

Astrocyte Glycogen Sustains Neuronal Activity during Hypoglycemia: Studies with the Glycogen Phosphorylase Inhibitor CP-316,819 ([R-R*,S*]-5-Chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide)

“…Two hours after the final injection, the rats were used for either brain glycogen determinations or hypoglycemia studies. For brain glycogen determinations, the rats were euthanized by high-energy (3 kW) focused microwave irradiation (Gerling Applied Engineering, Inc., Modesto, CA) (Swanson et al, 1990). Parietal cortex and hippocampus from both hemispheres was dissected free of underlying white matter and solubilized in 0.1 N NaOH/0.01% SDS for subsequent glycogen determinations by the amyloglucosidase method (Swanson et al, 1990).…”

Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia

“…As described in our previous study (Chen et al, 2005), 2 mm coronal slices were made and stained for 20 min at 37°C with 2% 2, 3, 5,-triphenyltetrazolium chloride monohydrate (TTC). Infarction volume was calculated using NIH image analysis software as described by Swanson et al (1990). Brain swelling in the ischemic hemisphere was taken into consideration during the analysis.…”

Postischemic (6-Hour) Treatment With Recombinant Human Tissue Plasminogen Activator and Proteasome Inhibitor PS-519 Reduces Infarction in a Rat Model of Embolic Focal Cerebral Ischemia

“…28 To reduce errors associated with processing of tissue for histological analysis, the ischemic volume is presented as the percentage of infarct volume of the contralateral hemisphere (indirect volume calculation). 29 …”