@entity191 ( @entity191 ) is characterized by progressive death of @entity935 (DA) neurons in the substantia nigra pars compacta. We report a @entity35 model that exhibits progressive death of nigral neurons following unilateral injection of @entity4176 in the striatum. In situ end-labeling revealed significant numbers of dying nigral neurons ipsilateral to the lesion during the first 3 weeks following injection. An indication of the gradual nature of death was that similar small numbers of cells were detected at each time point. These early morphological markers of @entity528 led to a significant reduction (20%) at 5 months of @entity669 hydroxylase-positive neurons and total number of neurons in the ipsilateral substantia nigra compared with the contralateral control. To examine the role of nigrostriatal DA metabolism in the observed nigral @entity528 , we manipulated DA metabolism during the initial 2 weeks following @entity4176 lesion. Neurons in the ventral tier of the substantia nigra pars compacta were protected from death by treatment with @entity24270 ( @entity54019 ), an inhibitor of @entity3007 cyclohydrolase, the initial enzyme in the synthesis of the @entity669 hydroxylase co-substrate, @entity8083 ( @entity8084 ). Neurons in both the dorsal and ventral tier of substantia nigra pars compacta were protected from death by treatment with DAHP and @entity3034 . These experiments suggest that intrastriatal @entity4176 lesion is an in vivo model of trophic support withdrawal. This experimental procedure is useful for studying mechanisms underlying protracted death of nigral DA neurons and may provide valuable mechanistic information relevant to understanding the etiology of @entity191 .

XXXX lesion-induced nigral @entity528 .

@entity3007 :: ('MESH:D006160', 'Chemical') :: ['GTP'] @entity3034 :: ('MESH:D007980', 'Chemical') :: ['L-DOPA'] @entity8083 :: ('MESH:C003402', 'Chemical') :: ['tetrahydrobiopterin'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity8084 :: ('CHEBI:15372', 'Chemical') :: ['BH(4)'] @entity24270 :: ('MESH:C017202', 'Chemical') :: ['2,4-diamino-6-hydroxy-pyrimidine'] @entity191 :: ('MESH:D010300', 'Disease') :: ["Parkinson's disease", 'PD'] @entity4176 :: ('MESH:D007608', 'Chemical') :: ['kainic acid'] @entity54019 :: ('MESH:C017182', 'Chemical') :: ['DAHP'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity528 :: ('MESH:D009410', 'Disease') :: ['neuronal death']
@entity4176 :: (MESH:D007608,Chemical) :: ['Kainic acid']
