FUNCTIONAL INJURY OF CHOLINERGIC, GABAERGIC AND DOPAMINERGIC SYSTEMS IN THE BASAL GANGLIA OF ADULT-RAT WITH KAOLIN-INDUCED HYDROCEPHALUS

Structural and/or functional injury of the basal ganglia can lead to m otor functional disabilities, abnormal gait and posture, and intellect ual/emotional impairment, disorders also frequently seen in hydrocepha lus. Previous reports have documented changes in dopamine levels in th e neostriatum in experimental hydrocephalus. The present study was des igned to investigate possible functional injury of cholinergic, GABAer gic and dopaminergic systems in the basal ganglia immunohistochemicall y in a model of kaolin-induced hydrocephalus. Hydrocephalus was induce d in 12 Wistar rats by intracisternal injection of 0.05 ml volume of 2 5% kaolin solution under microscopic guidance. Four controls received an equal volume of sterile saline. The animals were killed at 2, 4 and 8 weeks after injection. The numbers of choline acetyltransferase (Ch AT)- and glutamic acid decarboxylase (GAD)-immunoreactive (IR) neostri atal neurons and tyrosine hydroxylase (TH) - IP nigral neurons, were c ounted in 60-mu m thick representative sections and the IR cellular de nsities (counted cell number/neostriatal area) were calculated in the neostriatum. The number of total neostriatal neurons was also counted in 15-mu m thick sections stained by cresyl violet (Nissl staining) to calculate the cellular density. The number and cellular density of ne ostriatal ChAT-IR neurons were significantly reduced at 2, 4, and 8 we eks after injection (P < 0.05), while those of GAD-IR neurons decrease d at 4 and 8 weeks (P < 0.05). There was a linear correlation between degree of ventricular enlargement, and reduction in number of ChAT- an d GAD-IR neurons (P < 0.001) as well as in the cellular density (P < 0 .001). However, Nissl staining revealed no reduction in the cellular d ensity of total neostriatal neurons (P < 0.001). TH immunoreactivity w as reduced in neostriatal axons and in nigral compacta neurons, partic ularly in the medial portion of the dopaminergic nigrostriatal pathway . These findings suggest that progressive hydrocephalus results in fun ctional injuries of cholinergic and GABAergic neurons in the neostriat um and dopaminergic neurons in the substantia nigra compacta by mechan ical distortion. The disturbance in balance of these neurotransmitter systems in the basal ganglia may explain some of motor functional disa bilities in hydrocephalus. (C) 1997 Elsevier Science B.V.