Probing Caffeine Administration as a Medical Management for Hydrocephalus: An Experimental Study

Abstract

BackgroundHydrocephalus is currently managed by cerebrospinal fluid diversion from the cerebral ventricles to other body sites, but this is complicated by obstruction and infection in young infants, thus adding to morbidity and mortality. Studies have reported caffeine to be a pleiotropic neuroprotective drug in the developing brain due to its antioxidant, anti-inflammatory, and antiapoptotic properties, with improved white matter microstructural development. In this study, we investigate the use of caffeine administration as a possible means of pharmacological management for hydrocephalus. MethodsA total of 76 three-day-old mice pups from 10 dams were divided into four groups: hydrocephalus was induced in the pups in two groups by intracisternal injection of kaolin suspension, and their dams were given either caffeine (50 mg/kg by gavage) or water daily for 21 days; the dams in the other 2 (non-hydrocephalic) groups similarly had either caffeine or water; the pups received caffeine administered via lactation. Developmental neurobehavioral tests were performed until day 21, when the pups were sacrificed. Their brains were removed and processed for Cresyl and Golgi staining; both quantitative and qualitative analyses were then carried out. ResultsImproved developmental motor activities and reflexes were observed in the hydrocephalus + caffeine–treated pups. Caffeine administration was associated with reduced cell death and increased dendritic arborization of the neurons in the sensorimotor cortex and striatum of hydrocephalic mice pups. ConclusionCaffeine administration appears to have promise as an adjunct in hydrocephalus management, and its use needs to be further explored.