Dopamine transporter and nitric oxide synthase in hypoxic-ischemic brain

Changes in dopamine transporter and neuronal nitric oxide synthase (nNOS) w ere investigated by immunohistochemistry in 18 cases of hypoxic-ischemic ba sal ganglia necrosis, Neuropil dopamine transporter immunostaining in the s triatum was increased in seven cases, with relatively mild basal ganglia ne crosis, and decreased in four cases, with marked basal ganglia necrosis, co mpared with age-matched control subjects. Correspondingly, some striatal ne urons had increased immunoreactivity to dopamine transporter in the cases o f increased immunostaining in the neuropil, nNOS-positive neurons did not o bviously change in cases of basal ganglia necrosis within 2 days after birt h and then decreased or were not detectable in cases of basal ganglia necro sis at more than 3 days after birth. The results suggest that the synthesis of dopamine transporter is up-regulated in relatively mild basal ganglia n ecrosis to compensate for the uptake of increased dopamine, that this compe nsative ability is lost in marked basal ganglia necrosis, and that nNOS-con taining neurons in the striatum are relatively resistant to hypoxic ischemi a, We speculate that glutamate excitotoxicity mediated by glutamate recepto rs 1, 2/3, and 4 and excessive dopaminergic excitatory activity may play im portant roles in hypoxic-ischemic basal ganglia necrosis and that nNOS does not contribute to that condition. (C) 2000 by Elsevier Science Inc. All ri ghts reserved.