Changes in AMPA glutamate and dopamine D2 receptors in hypoxic-ischemic basal ganglia necrosis

Changes in the AMPA glutamate receptor subunits (GluR1, 2-3, and 4) and dopamine D2 receptor (D2R) were investigated in 16 cases of hypoxic-ischemic basal ganglia necrosis (BGN) by immunohistochemistry. Immunoreactivity to GluR1, 2-3, and 4 was observed in the cytoplasm and dendrites of small and large neurons in the basal ganglia. Neuronal immunoreactivity to GluR1, 2-3, and 4 was decreased in cases with acute BGN as compared with that in age-matched controls, the areas of decreased immunoreactivity corresponding to the damaged regions observed on hematoxylin and eosin staining. Glia in the basal ganglia exhibited immunoreactivity to GluR4 in 4 patients with acute BGN, 3 of the 4 surviving for 12 to 35 days. In addition, neuronal immunoreactivity to D2R was also decreased in cases of acute BGN, the decrease being similar to that of GluR1, 2-3, and 4. Our results suggest that excitotoxicity mediated by GluR1, 2-3, and 4 is involved in the pathogenesis of hypoxic-ischemic neuronal damage, and that GluR4 expressed in glia of the BG in the late stage of hypoxic-ischemic injury may participate in the delayed and long-term response of the glia to injury. The decrease in neuronal D2R may be related to downregulated synthesis of the D2R protein induced by the decrease in GluR1-4 in the basal ganglia.