The research is directed toward an examination of the toxic effects of lead on systems regulating intracranial pressure and fluid dynamics. OUR PRELIMINARY STUDIES show an age-dependent disturbance in the mechanism for reabsorption of cerebrospinal fluid (CSF) with exposure to lead during the neonatal period. We plan to extend those studies and examine intracranial fluid dynamics following delivery of lead pre-natally, during periods of neurovascular proliferation. A RABBIT MODEL will be used with timed maternal exposure to lead during gestation and subsequent testing of the offspring at intervals after birth. EXPERIMENTAL END POINTS include quantitative assessment of: 1.) CSF reabsorption into the intracranial venous sinuses; 2.) intracranial compliance; 3.) CSF formation rates; and 4.) tissue lead levels. EXPERIMENTS will be directed toward establishing 1.) a dose/response profile for maternal lead exposure; 2.) the effects of timing of lead exposure during gestation; and 3.) assessing the vulnerability to physiologic and pharmacologic stresses with respect to CSF dynamics in animals exposed to lead during gestation. NEW METHODOLOGY will be utilized by application of our model system to the isolated superior sagittal sinus of the dog. Promising preliminary results suggest that this in vitro technique will considerably enhance our understanding of the natural physiology, biochemistry, and morphology of that structure and will allow a direct assessment of the toxic effects of lead on the mechanism for reabsorption of CSF. The significance of the research relates to the major health problems of congenital hydrocephalus, conditions associated with brain edema, and maternal lead exposure during pregnancy
NIH ExPorter
NIH ExPorter