Persistent region-dependent neuroinflammation, NMDA receptor loss and atrophy in an animal model of penetrating brain injury

Dynamic changes in neuroinflammation and glutamate NMDA receptors (NMDAR) have been noted in traumatic and ischemic brain injury. Aim: Here we investigate the time course and regional distribution of these changes and their relationship with atrophy in a rat model of penetrating brain injury. Materials & methods: Quantitative autoradiography, with the neuroinflammation marker [ ³H]PK11195 and the NMDAR antagonist [ ¹²⁵I]iodoMK801, was performed on brains of animals subjected to a unilateral wireknife injury at the level of striatum and killed 3-60 days later. Regional atrophy was measured by morphometry. Results: The injury produced large increases in [ ³H]PK11195 binding density in cortical and septal regions adjacent to the knife track by day 7, with modest increases in the striatum. [ ¹²⁵I]iodoMK801 binding was reduced in cortical and hippocampal regions showing marked neuroinflammation, which showed marked atrophy at subsequent time points. Conclusion: These results indicate that neuroinflammaton and loss of NMDAR precede and predict tissue atrophy in cortical and hippocampal regions.