Intracranial hypertension in vitamin A deficient rats: reversible metabolic derangement of cerebrospinal fluid absorption

Increased intracranial pressure induced by deficiency of vitamin A (Vit A) in man and experimental animals has been attributed to structural abnormalities of cerebrospinal fluid (CSF) circulatory pathways presumably resulting from enhanced activity of calvarium osteoblasts and arachnoidal fibroblasts. In the present study classical signs of Vit A deficiency were produced in rats fed a selectively deficient diet for 12 weeks beginning in the weaning period, and these animals were then compared to ad lib and pair-fed controls. When deficient rats showed a precipitous 25 percent decline in body weight associated with barely detectable concentrations of retinol in liver and plasma, manometric assessment of CSF dynamics was performed using a graded series of low-volume, constant rate infusions of artificial CSF into the spinal subarachnoid space. Capacity of arachnoid villi for CSF absorption by combined action of transport (M) and valvelike (P(R)) mechanisms was calculated according to a previously developed mathematical model. Vit A deficient rats showed a 12-fold increase in CSF outflow resistance, which could be attributed to compromise of P(R) with only minimal changes in M; although there was a compensatory decline in CSF production, intracranial compliance was unaffected. Additionally, 4 weeks of Vit A replacement not only reversed the stigmata of the deficiency state, but was associated with almost complete normalization of the CSF outflow resistance. We suggest that intracranial hypertension induced by Vit A deficiency results from a reversible structural derangement of arachnoid villi, which impedes efflux of newly formed CSF.