Reduced Local Cerebral Blood Flow in Periventricular White Matter in Experimental Neonatal Hydrocephalus—Restoration with CSF Shunting

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Abstract
The extent to which the reduction in CBF occurring in hydrocephalus is a primary or secondary event in the pathogenesis of the brain injury that ensues has not been clearly established. This is particularly true in neonatal hydrocephalus, where the disorder is most common, and where timing of the treatment of the developing nervous system is so important. We investigated the changes in local CBF (lCBF) in an animal model of severe progressive neonatal hydrocephalus before and after CSF shunting. Hydrocephalus was induced in 27 1-week-old kittens by percutaneous injection of 0.05 ml of 25% kaolin into the cisterna magna. Fourteen littermates acted as controls. The lCBF was measured by 14C-iodoantipyrine quantitative autoradiography after 1 week in 15 animals (8 hydrocephalic, 7 controls) and after 3 weeks in 26 animals (19 hydrocephalic, 7 controls) following induction of hydrocephalus. Twelve of the 3-week hydrocephalic group received a ventriculoperitoneal shunt 10 days following kaolin injection. At 1 week following induction of hydrocephalus, lCBF was globally reduced in cortical gray matter and white matter as well as deep subcortical structures. The maximum reduction was in the parietal white matter, to 37% of control levels. At 3 weeks a significant reduction in lCBF persisted only in the white matter (parietal, occipital, and corpus callosum; average, 42% of control levels), whereas cortical gray and deep subcortical structures had returned to normal levels spontaneously. lCBF was normal in 3-week hydrocephalic shunted animals in all areas. CSF shunting restores the fall in lCBF in the periventricular white matter in this model. These findings are consistent with previous studies in the same model demonstrating derangement of high-energy phosphate metabolism and white matter anaerobic glycolysis with hydrocephalus and resolution with shunting.