Effects of Hydrocephalus and Surgical Decompression on Cortical Norepinephrine Levels in Neonatal Cats

Abstract

Abstract Norepinephrine (NE) changes during hydrocephalus, and the effects of surgical decompression on these changes, were studied using a new model of neonatal hydrocephalus. Kittens 4 to 10 days old received intracisternal injections of a sterile solution of 25% kaolin. Control kittens were injected similarly with sterile injectable saline. Ultrasonography was used to follow the progression of ventriculomegaly and the initial effects of the shunts. A subgroup of hydrocephalic animals was shunted using a cerebrospinal fluid lumbar-peritoneal catheter. Hydrocephalic animals were killed at approximately 25 days of age (16-21 days after kaolin injection). Surgical decompression was performed at 12, 16, and 17 days after kaolin injection; these animals were killed 30 days after the shunts were inserted. Control animals were killed at 29 and 53 days of age, to correlate with the ages of the hydrocephalic and shunted animals, respectively. Cortical samples equivalent to Brodmann's areas 4, 22, and 17 were measured for NE using high-performance liquid chromatography. Hydrocephalus caused NE levels to decrease significantly in all cortical areas. These alterations followed a rostrocaudal gradient in severity, with mean reductions of 65.8, 83.9, and 95.8% in areas 4, 22, and 17, respectively. Partial recovery occurred in animals that received shunts 16 and 17 days after kaolin injection, such that NE reductions of 75.7, 56.2, and 81.6% were noted in areas 4, 22, and 17, respectively. Shunting at 12 days after kaolin injection produced complete recovery in areas 4 and 22, with only a 67.7% decrease in area 17. These results suggest that the projection fibers from the locus ceruleus are damaged by the direct effects of hydrocephalus. Axotomy or neuropraxia of these fibers could result in decreases in NE throughout the cerebral cortex. In addition, there appears to be a period of time during which surgical decompression will allow neuropraxic fibers to recover with partial restoration of NE levels. Earlier insertion of a shunt appears to allow for more recovery than later decompression.