kaolinite and Brain-Damage--Chronic

Juvenile rats with kaolin-induced hydrocephalus have reduced brain injury if treated with nimodipine or magnesium sulfate. Experiments were conducted to determine if the neuroprotective effects could be replicated in neonatal rats with experimental hydrocephalus at an age comparable to prematurely born humans. In a blinded and randomized manner, drugs were administered for 14 days beginning 7 days after induction of hydrocephalus. Nimodipine was given twice daily by subcutaneous injections. Daily doses greater than 38 mg/kg of body weight were fatal. Daily doses of 3.8 to 30 mg/kg were not associated with behavioral, structural, or biochemical improvements. Magnesium chloride was administered via daily subcutaneous minipump infusion (0.87 or 1.74 mM/kg) along with twice daily injections of 0.74 or 1.48 mM/kg. Magnesium sulfate was administered by twice daily subcutaneous doses of 1.54 or 7.72 mM/kg. Sedation occurred, but there was no statistically significant protection in regard to behavior, brain structure, or brain composition in any of the magnesium experiments. Developmental alterations in calcium channels of the neonatal rat brain could account for differences from prior experiments in young hydrocephalic rats.

Topics: Animals; Animals, Newborn; Brain; Brain Damage, Chronic; Calcium Channel Blockers; Calcium Channels; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hydrocephalus; Infusion Pumps; Kaolin; Lateral Ventricles; Magnesium Chloride; Magnesium Compounds; Magnesium Sulfate; Male; Nerve Fibers, Myelinated; Neuroprotective Agents; Nimodipine; Rats; Rats, Sprague-Dawley; Survival Rate; Treatment Outcome

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