Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain as measured with 1H Nuclear Magnetic Resonance Imaging

The aim of this study is to characterize the evolution of excitotoxic damage in neonatal rat brain by diffusion-weighted and T2-weighted magnetic resonance imaging. Results are compared with histological findings. Magnetic resonance imaging was performed at various times (15 min, 24 h, 3 days and 5 days) after intrastriatal microinjection of N-methyl-d-aspartate (NMDA) at postnatal day 8. The transverse relaxation time (T2) and apparent diffusion coefficient of water were determined. The results show an acute reduction of the apparent diffusion coefficient, reflected by an ipsilateral hyperintensity in the diffusion-weighted images, within 15 min after intrastriatal NMDA injection. At this time no changes in the T2-weighted images were apparent. The volume of the hyperintensity was relatively large with a radius of approximately 2 mm and coincided with histological signs of pronounced karyo-dendritic swelling. Subcutaneous administration of MK-801 25 min after the intracerebral NMDA injection readily reversed the hyperintensity and resulted in complete protection as verified by histology. Areas with increased T2 values were observed 1 day after NMDA microinjection and corresponded to regions with obvious cell necrosis. Five days after NMDA injection the lesion was evident using both diffusion- and T2-weighted images and coincided with an overt lesion comprising areas of cell loss and dilatation of the ipsilateral ventricle. In conclusion, this study illustrates the possibility of using diffusion-weighted imaging as a tool to monitor efficacy of treatment strategies at an early stage of excitotoxic injury

Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat : evidence for region-specific sensitivity and delayed damage

Background and Purpose: Selective regional sensitivity and delayed damage in cerebral ischemia provide opportunities for directed and late therapy for stroke. Our aim was to characterize the spatial and temporal profile of ischemia-induced changes in cerebral perfusion and tissue status, with the use of noninvasive MRI techniques, to gain more insight in region-specific vulnerability and delayed damage. Methods: Rats underwent 20 minutes of unilateral cerebral hypoxia-ischemia (HI). We performed combined repetitive quantitative diffusion-weighted, T2-weighted, and dynamic susceptibility contrast-enhanced MRI from before HI to 5 hours after HI. Data were correlated with parallel blood oxygenation level-dependent MRI and laser-Doppler flowmetry. Finally, MRI and histology were done 24 and 72 hours after HI. Results: Severe hypoperfusion during HI caused acute reductions of the apparent diffusion coefficient (ADC) of tissue water in the ipsilateral hemisphere. Reperfusion resulted in dynamic perfusion alterations that varied spatially. The ADC recovered completely within 1 hour in the hippocampus (from 0.68 +/- 0.07 to 0.83 +/- 0.09x10 sup -3 mm2/s), cortex (from 0.56 +/- 0.06 to 0.77 +/- 0.07x10 sup -3 mm2/s), and caudate putamen (from 0.58 +/- 0.06 to 0.75 +/- 0.06x10 sup -3 mm2/s) but only partially or not at all in the thalamus (from 0.65 +/- 0.07 to 0.68 +/- 0.12x10 sup -3 mm2/s) and substantia nigra (from 0.80 +/- 0.08 to 0.76 +/- 0.10x10 sup -3 mm2/s). Secondary ADC reductions, accompanied by significant T2 elevations and histological damage, were observed after 24 hours. Initial and secondary ADC decreases were observed invariably in the hippocampus, cortex, and caudate putamen and in approximately 70% of the animals in the thalamus and substantia nigra. Conclusions: Region-specific responses and delayed ischemic damage after transient HI were demonstrated by MRI. Acute reperfusion-induced normalization of ADCs appeared to poorly predict ultimate tissue recovery since secondary, irreversible damage developed eventually