Decreased c-fos expression in experimental neonatal hydrocephalus: evidence for reduced neuronal activation.
Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a "third messenger" to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.
McAllister
J P
JP
Departments of Neurological Surgery, Anatomy, and Cell Biology, Wayne State University School of Medicine, University Health Center, Detroit, Michigan; Departments of Neurosurgery, and Biostatistics and Epidemiology, The Cleveland Clinic Foundation, Cleveland, Ohio; and Department of Pharmacology and Therapeutics, University of Florida, Health Science Center, Gainesville, Florida.
Wood
A S
AS
Johnson
M J
MJ
Connelly
R W
RW
Skarupa
D J
DJ
Secic
M
M
Luciano
M G
MG
Harris
N G
NG
Jones
H C
HC