Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalus.
The deleterious effects of hydrocephalus, a disorder that primarily affects children, include reactive astrocytosis, microgliosis and inflammatory responses; however, the roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. Therefore we have examined neuroinflammation at both the cellular and the molecular levels in an experimental model of neonatal obstructive hydrocephalus. On post-natal day 1, rats received an intracisternal injection of kaolin to induce hydrocephalus; control animals received saline injections. Prior to sacrifice on post-natal day 22, animals underwent magnetic resonance imaging to quantify ventricular enlargement, and the parietal cortex was harvested for analysis. Immunohistochemistry and light microscopy were performed on 5 hydrocephalic and 5 control animals; another set of 5 hydrocephalic and 5 control animals underwent molecular testing with Western blots and a gene microarray. Scoring of immunoreactivity on a 4-point ranking scale for GFAP and Iba-1 demonstrated an increase in reactive astrocytes and reactive microglia respectively in the hydrocephalic animals compared to controls (2.90±0.11 vs. 0.28±0.26; 2.91±0.11 vs. 0.58±0.23, respectively). Western blots confirmed these results. Microarray analysis identified significant (1.5-fold) changes in 1729 of 33,951 genes, including 26 genes out of 185 genes (26/185) in the cytokine-cytokine receptor interaction pathway, antigen processing and presentation pathways (15/66), and the apoptosis pathway (10/69). Collectively, these results demonstrate alterations in normal physiology and an up-regulation of the inflammatory response. These findings lead to a better understanding of neonatal hydrocephalus and begin to form a baseline for future treatments that may reverse these effects.
Deren
Kelley E
KE
Department of Neurosurgery, Division of Pediatric Neurosurgery, Primary Children's Medical Center, and The University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA. kelley.deren@hsc.utah.edu
Packer
Melissa
M
Forsyth
Jennifer
J
Milash
Brett
B
Abdullah
Osama M
OM
Hsu
Edward W
EW
McAllister
James P
JP
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002552:Cerebral Ventricles / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004660:Encephalitis / Q000235:genetics / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005911:Gliosis / Q000235:genetics / Q000473:pathology*; D006849:Hydrocephalus / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D046228:Microarray Analysis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines