Metabolic Responses of the Neonatal Rabbit Brain to Hydrocephalus and Shunting

Abstract

The metabolic changes that occur in the neonatal brain as a result of hydrocephalus, and the response to ventriculoperitoneal shunting, vary with the maturational stage of the brain. In this study, local glucose utilization (LCMRglu) and oxidative metabolic capacity were estimated using 2-deoxyglucose autoradiography and cytochrome oxidase histochemistry, respectively. Hydrocephalus was induced in rabbit pups via intracisternal kaolin injections at 4-6 days of age. Shunting occurred at 19–26 days of age and the animals were sacrificed at ages ranging from 33 to 331 days. In normal animals there was a high glucose demand early in life which showed a decrease at about 60 days of age. In rabbits sacrificed prior to 60 days of age the controls showed the highest LCMRglu with significant decreases in both the hydrocephalic and shunted animals. After 60 days of age the shunted animals had higher LCMRglu than both the hydrocephalic and control subjects. Oxidative metabolic capacity peaked before 50 days of age in normal animals. At the youngest age, both the hydrocephalic and shunted animals showed higher cytochrome oxidase density rates than the control rabbits. In the older group, the hydrocephalic animals remained high while the shunted animals approximated the control densities. Neither the changes seen in the LCMRglu nor the oxidative metabolic capacity were correlated with changes in cell packing density or increased intracranial pressure. These data suggest that when the brain is compromised by hydrocephalus, there is an initial compensatory increase in oxidative metabolic capacity. The development of the glycolytic pathway appears to be retarded by hydrocephalus, but with shunting and the passage of time, the LCMRglu rebounds to levels above that of controls.

Mitochondrial cytochrome c oxidase expression in the central nervous system is elevated at sites of pressure gradient elevation but not absolute pressure increase

“…An increase in CcO levels in regions of pressure gradient elevation after axonal structural and functional changes had taken place (Balaratnasingam et al,2008) suggests that a change in CcO levels may be a compensatory response by mitochondria to limit and potentially reverse axonal injury. Our finding is also consistent with previous work that has demonstrated increased cytochrome oxidase activity in hydrocephalic brains (Wehby‐Grant et al,1996), suggesting that an increase in neuronal pressure gradients within the brain results in a compensatory response by mitochondria to increase metabolic activity. An increase in mitochondrial energy production secondary to pressure gradient changes may also aid in the development of neuronal tolerance that is known to occur in hydrocephalus (Ding et al,2001).…”

Progressive Changes in Cortical Metabolites at Three Stages of Infantile Hydrocephalus Studied byIn VitroNMR Spectroscopy

“…These factors may make the tissue more vulnerable to traumatic injury than at other ages and explain why shunt treatment is less effective if delayed to this age (Harris et al, 1996b. This is consistent with kaolin-induced hydrocephalus in rabbit pups where glucose utilization was more severely and irreversibly compromised in animals prior to 60 days than in older animals (Wehby-Grant et al, 1996). There is considerable evidence that the rat cerebral cortex at 10 days after birth is equivalent to that of a newborn human infant (Romijn et al, 1991), suggesting that newborn infants may also be very much at risk from damage due to hydrocephalus.…”

Acute and Subacute Hydrocephalus in a Rat Neonatal Model: Correlation with Functional Injury of Neurotransmitter Systems

“…Del Bigio et al [1]also described the death of some models with infantile hydrocephalus 4 weeks following injection. Although there were many studies about kaolin-induced hydrocephalus in immature animals, they used only acute type [6, 12, 14, 28]or two kinds of the models together without discrimination [1, 11, 29]. …”

“…There have been many reports of animal models in which the pathological changes of brain were investigated to determine the mechanism of neuronal damages in hydrocephalus. Likely mechanisms may include mechanical distortion [3, 4, 5], ischemic effects [6, 7]and metabolism which includes impairment of the removal of waste products [8, 9, 10, 11]. …”

“…There have also been many studies about recovery in the physiological metabolism and morphological structure of neonatal hydrocephalus with shunt placement [2, 8, 9, 11, 12, 13]. The condition of the neonatal brain is very different from that of the adult brain in neuronal development, myelination and cranial vault mechanics with open sutures and fontanel.…”