kaolinite and Learning-Disabilities

Ventriculomegaly occurs when there is imbalance between creation and absorption of cerebrospinal fluid (CSF); even when treated, long-term behavioral changes occur. Kaolin injection in the cisterna magna of rats produces an obstruction of CSF outflow and models one type of hydrocephalus. Previous research with this model shows that neonatal onset has mixed effects on Morris water maze (MWM) and motoric performance; we hypothesized that this might be because the severity of ventricular enlargement was not taken into consideration. In the present experiment, rats were injected with kaolin or saline on postnatal day (P)21 and analyzed in subgroups based on Evan's ratios (ERs) of the severity of ventricular enlargement at the end of testing to create 4 subgroups from least to most severe: ER0.4-0.5, ER0.51-0.6, ER0.61-0.7, and ER0.71-0.82, respectively. Locomotor activity (dry land and swimming), acoustic startle with prepulse inhibition (PPI), and MWM performance were tested starting on P28 (122cm maze) and again on P42 (244cm maze). Kaolin-treated animals weighed significantly less than controls at all times. Differences in locomotor activity were seen at P42 but not P28. On P28 there was an increase in PPI for all but the least severe kaolin-treated group, but no difference at P42 compared with controls. In the MWM at P28, all kaolin-treated groups had longer path lengths than controls, but comparable swim speeds. With the exception of the least severe group, probe trial performance was worse in the kaolin-treated animals. On P42, only the most severely affected kaolin-treated group showed deficits compared with control animals. This group showed no MWM learning and no memory for the platform position during probe trial testing. Swim speed was unaffected, indicating motor deficits were not responsible for impaired learning and memory. These findings indicate that kaolin-induced ventriculomegaly in rats interferes with cognition regardless of the final enlargement of the cerebral ventricles, but final size critically determines whether lasting locomotor, learning, and memory impairments occur.

Topics: Animals; Chronic Disease; Disease Models, Animal; Hydrocephalus; Kaolin; Learning Disabilities; Male; Maze Learning; Memory Disorders; Mental Disorders; Movement Disorders; Rats; Rats, Sprague-Dawley; Weaning

The septohippocampal cholinergic (SHC) system plays an important role in the maintenance of normal memory and learning. However, the fact that memory and learning impairments under hydrocephalic conditions are directly related to the SHC system is less well known. We investigated the relationships between pathological changes in SHC neurons and impairments in memory and learning among hydrocephalic rats.. Rats with kaolin-induced hydrocephalus were prepared with injections of kaolin suspension into the cisterna magna. Learning and memory performance was assessed with the passive avoidance and Morris water maze tests. Ventricular sizes were measured for the lateral and third ventricles. Acetylcholinesterase and choline acetyltransferase immunostaining was performed to investigate degenerative changes in cholinergic neurons in the medial septum and hippocampus.. Hydrocephalic rats demonstrated significant learning and memory impairments in the passive avoidance and Morris water maze tests. Decreased hesitation times in the passive avoidance test and markedly increased acquisition times and decreased retention times in the Morris water maze test indicated learning and memory dysfunction among the hydrocephalic rats. The numbers of cholinergic neurons in the medial septum and hippocampus were decreased in the hydrocephalic rats. The decreases in choline acetyltransferase and acetylcholinesterase immunoreactivity were significantly correlated with enlargement of the ventricles.. Impairment of spatial memory and learning may be attributable to degeneration of SHC neurons. These results suggest that learning and memory impairments in rats with kaolin-induced hydrocephalus are associated with the dysfunction of the SHC system induced by ventricular dilation.

Topics: Animals; Antidiarrheals; Avoidance Learning; Cholinergic Fibers; Disease Models, Animal; Hippocampus; Hydrocephalus; Kaolin; Learning Disabilities; Male; Maze Learning; Memory Disorders; Rats; Rats, Sprague-Dawley; Septum of Brain

The motor and cognitive dysfunction associated with hydrocephalus remains a clinical problem in children. We hypothesized that young rats with hydrocephalus should exhibit similar dysfunction and that the dysfunction should be reversible by shunting. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. Rats were assessed by T2-weighted images obtained with a 7-T magnetic resonance device and by repeated behavioral testing including ability to traverse a narrow beam and ability to find a hidden platform in a water pool. Some of the rats underwent a shunting procedure 1 or 4 weeks after kaolin injection. Magnetic resonance images were used to measure ventricle size. They clearly demonstrated increased signal in periventricular white matter, which corresponded to increased brain water content. A flow-void phenomenon was observed in the cerebral aqueduct. Ability to traverse the beam did not correlate with the degree of ventriculomegaly. Ability to swim to the hidden platform demonstrated a progressive impairment of learning function which may have been accentuated by motor disability. When rats were shunted after 1 week, the behavioral dysfunction was prevented. Late shunting after 4 weeks was associated with gradual recovery of the behavioral disability which was not complete after 4 weeks. We conclude that early shunting is superior to late shunting with regard to behavioral dysfunction. High-resolution MR imaging shows features in hydrocephalic rats similar to those found in hydrocephalic humans.

Topics: Animals; Behavior, Animal; Brain Damage, Chronic; Cerebral Ventricles; Cerebrospinal Fluid Shunts; Cognition Disorders; Hydrocephalus; Kaolin; Learning Disabilities; Magnetic Resonance Imaging; Maze Learning; Movement Disorders; Postoperative Period; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Time Factors