Acute and Subacute Hydrocephalus in a Rat Neonatal Model: Correlation with Functional Injury of Neurotransmitter Systems

Abstract

Object: The evolution and severity of hydrocephalus in animal models varies in the species and mode of induction. This makes comparisons of the physiological system under investigation difficult between models. We noted that injection of kaolin into neonatal rats results in a dichotomous outcome into either an acute or subacute form. We investigated the clinical and functional transmitter system changes to compare these two types of hydrocephalus evolution. Methods: Hydrocephalus was induced in Wistar neonatal rats (within a week after their birth) by intracisternal injection of 0.02 ml volume of 25% kaolin solution under microscopic guidance. The same volume of sterile saline was injected into 12 neonatal rats as control group. The animals were assigned to either the acute or subacute group according to their head size, and sacrificed at 2, 4 and 8 weeks after injection. Biparietal diameter, ventricular size, cholinergic interneurons in the neostriatum and dopaminergic projection neurons in the substantia nigra were analyzed at each stage. Results: Animals affected with the acute type of hydrocephalus had obvious head enlargement, rapid ventricular enlargement, and all died at about 4 weeks. Animals with subacute type had slowly progressive ventricular enlargement, and all survived until 8 weeks. There appeared to be more kaolin ventral to the brainstem in the acute type. The number of cholinergic neostriatal neurons was significantly reduced at 2 and 4 weeks in the acute type, but only at 8 weeks in the subacute type. The number of dopaminergic nigral neurons was decreased at 4 weeks in the acute type, but unaffected in the subacute type. Conclusions: The severity of onset of hydrocephalus in this animal model also correlates with the clinical outcome and changes in functional transmitter systems.

Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood

“…The long-term effects of hydrocephalus in the rat have been studied predominantly in the kaolin (aluminium silicate) model. However, hydrocephalus has only been induced within the first week of birth in a few studies [14,[22][23][24][25][26][27]. None of these investigates longterm survival beyond 8 weeks.…”

Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

“…In animal models, monoamine neurotransmitter concentrations are decreased [268-269]; while reductions in cholinergic and dopaminergic neurons in particular brain regions have also been demonstrated [270-271]. Much of the literature regarding neurotransmitters is related to the association between hydrocephalus and Parkinsonism’s, rarely akinetic mutism, and other movement disorders [272-275].…”

Neuropathology and structural changes in hydrocephalus

“…The upregulation of growth-associated protein (GAP-43), nerve growth factor, and other protective proteins in experimental hydrocephalus [Miyajima et al, 1996;Zhang and Del Bigio, 1998;Shinoda et al, 2001;Balasubramaniam and Del Bigio, 2002] might be associated with synaptic remodeling or may be an impotent attempt to protect the axons. Changes in the content of monoamine neurotransmitters are a consequence of experimental hydrocephalus [Del Bigio, 1993;Otsubo et al, 1997;Del Bigio et al, 1998;Ishizaki et al, 2000]. Although neuronal changes in the striatum are not typically identifiable at the microscopic level, there is some imaging evidence for functional changes in dopamine receptors .…”