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

Abstract

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. Obstructive hydrocephalus was induced in 10-day-old kittens by intracisternal injections of 25% kaolin. Acute non-shunted animals were killed 15days post-kaolin injection to represent the pre-shunt condition. Shunt-treated animals received ventriculoperitoneal shunts 15days post-injection and were killed 10 or 60days later to represent short- and long-term recovery periods. Chronic untreated animals had Ommaya reservoirs implanted 15days post-kaolin, which were tapped intermittently until they were killed 60days 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. 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. 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.