DEVELOPMENTAL-CHANGES IN NMDA-INDUCED CELL SWELLING AND ITS TRANSITION TO NECROSIS MEASURED WITH H-1 MAGNETIC-RESONANCE-IMAGING, IMPEDANCE AND HISTOLOGY

The vulnerability of the rat brain to intracerebrally injected N-methy l-D-aspartate (NMDA) drastically changes with age. We evaluated the de velopmental changes in the early and late responses to NMDA using H-1 magnetic resonance imaging (MRI), cortical impedance and histology. NM DA, injected in the striatum of rats at postnatal days (P) 4, 7, 10, 1 4 and 21, induced a significant age-dependent reduction in the apparen t diffusion coefficient (ADC) of tissue water in the striatum and the cerebral cortex monitored 1 h later using diffusion-weighted MRT. The reduction in ADC amounted 65% at P4 with lower values thereafter and w as about 30% at P21. NMDA similarly induced a reduction in the cortica l extracellular space (by 50% at P7 and 10% at P16) as measured with i mpedance recordings. The progressive decrease in the effect of NMDA wi th brain development was also indicated by a decrease in the volume of tissue in which the changes in ADC occurred (50 mm(3) at P4 and 8 mm( 3) at P21). The diffusion of extracellular tracer molecules Mn2+ or -3 ]-(R)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA ) injected in the striatum and monitored with T-1-weighted MRI and aut oradiography respectively showed a similar age dependence with the dif fusion volume being twofold larger in P7 than in P21 brain. Thus restr iction in diffusion during brain development may contribute to the dec rease in NMDA-induced injury with age. The volume of tissue necrosis a nd gliosis, measured with T-2-weighted MRI and histology 5 days after NMDA injection, was similar to that outlined by the ADC reduction dete cted soon after the insult at P4, P7 and P21. However, at P10 and P14 only 50% of the tissue showing a hyperintense signal in DW images disp layed necrosis and gliosis 5 days later. This study shows that during development the early response to NMDA in terms of cytotoxic cell swel ling (indicated both with impedance recordings and diffusion-weighted MRI) decreases with age. In addition, with maturation only part of the brain tissue acutely affected by NMDA does proceed into necrosis and gliosis, indicating an increased capacity of cells in the developing r at brain to survive NMDA-induced cell swelling.