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Reactive astrocytosis in feline neonatal hydrocephalus: acute, chronic, and shunt-induced changes

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Abstract

Purpose

Reactive astrocytosis has been implicated in injury and recovery patterns associated with hydrocephalus. To investigate temporal changes in astrogliosis during the early progression of hydrocephalus, after shunting, and after long-term ventriculomegaly, glial fibrillary protein (GFAP) levels were analyzed in a feline model.

Methods

Obstructive hydrocephalus was induced in 10-day-old kittens by intracisternal injections of 25% kaolin. Acute non-shunted animals were killed 15 days post-kaolin injection to represent the pre-shunt condition. Shunt-treated animals received ventriculoperitoneal shunts 15 days post-injection and were killed 10 or 60 days later to represent short- and long-term recovery periods. Chronic untreated animals had Ommaya reservoirs implanted 15 days post-kaolin, which were tapped intermittently until they were killed 60 days later. Ventriculomegaly was monitored by neuroimaging before and after shunting and at death. RNA and total protein from primary visual cortex were analyzed by Northern and Western blotting.

Results

GFAP RNA and protein levels for acute and chronic non-shunted hydrocephalic animals were 77% and 247% (p < 0.01) and 659% (p < 0.05) and 871% (p < 0.05) higher than controls, respectively. Shunted animals with short-term recovery demonstrated a mismatch in GFAP levels, with RNA expression decreasing 26% and protein increasing 335% (p < 0.01). Shunted animals with a long-term recovery exhibited GFAP RNA and protein levels 201% and 357% above normal, respectively.

Conclusions

These results indicate that a reactive astrocytic response continues to rise dramatically in chronic hydrocephalus, suggesting ongoing gliosis and potential damage. Shunting partially ameliorates the continuation of astrogliosis, but does not completely reverse this inflammatory reaction even after a long recovery.

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Acknowledgments

This work was supported by the Department of Neurosurgery and Division of Pediatric Neurosurgery at the University of Utah, the Cleveland Clinic Foundation, and the Leede Hydrocephalus Research Fund. We thank William E. Bingaman, MD, and Narongsak (Ab) Boonswang, MD, for conducting much of the experimental work and Kristin Kraus, MSc, for editorial assistance with this paper.

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  1. Division of Pediatric Neurosurgery, Department of Neurosurgery, University of Utah, 175 North Medical Drive, Salt Lake City, UT, 84132, USA

    Ramin Eskandari, Carolyn A. Harris & James P. McAllister II

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  1. Ramin Eskandari
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  3. James P. McAllister II
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Correspondence to James P. McAllister II.

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Eskandari, R., Harris, C.A. & McAllister, J.P. Reactive astrocytosis in feline neonatal hydrocephalus: acute, chronic, and shunt-induced changes. Childs Nerv Syst 27, 2067–2076 (2011). https://doi.org/10.1007/s00381-011-1552-4

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