Glycine site antagonist attenuates infarct size in experimental focal ischemia. Postmortem and diffusion mapping studies.

Background And Purpose: The glycine site on the N-methyl-D-aspartate (NMDA) receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of most side effects associated with competitive and noncompetitive NMDA antagonists.

Methods: A novel glycine receptor antagonist, ZD9379, was studied in 70 Sprague-Dawley rats using the suture occlusion model of permanent middle cerebral artery occlusion (MCAO). In the first experiment, 20 rats received an initial bolus of vehicle or 10 mg/kg ZD9379 (n = 10 in each group) 30 minutes after MCAO, followed by a continuous infusion of the same dose per hour for 4 hours.

Severe transient hypoglycemia causes reversible change in the apparent diffusion coefficient of water.

Background And Purpose: The aim of this study was to determine the effects of temporary severe hypoglycemia on the apparent diffusion coefficient (ADC) acquired by diffusion-weighted MRI of brain water with the use of serial multislice ADC mapping in rats. Severe hypoglycemia reduces the extracellular space volume, as does ischemia. Demonstrating a reduction of ADC with hypoglycemia should increase our understanding of the mechanisms underlying ADC changes in ischemia and other conditions.

The role of spreading depression in focal ischemia evaluated by diffusion mapping.

This study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occlusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCl group; n = 7) and saline (NaCl group; n = 5) was performed at 15, 30, 45, and 60 minutes following MCAO, and SD was detected electrophysiologically.

Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain.

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.

Spreading waves of decreased diffusion coefficient after cortical stimulation in the rat brain.

A method is demonstrated for the noninvasive detection and study of spreading cortical depression. Spreading depression (SD) was elicited in rats by topical application of potassium chloride to the exposed cortex. The apparent diffusion coefficient (Dapp) of water in a region of the cortex, measured using a PFG-NMR spin echo sequence with an observation time of 40 ms, declines 35% within 30 s and recovers to the normal value within the next 30 s.