In this proposal we will study the effects of resting and elevated CSF steady-state pressures (CSFSSP) on physiologic and ultrastructural changes in various known and proposed intracranial pathways for CSF absorption. These pathways for transport of CSF out of the intracranial compartment include 1) arachnoid villi, 2) transnasal CSF flow into cervcal lymphatics, and 3) CSF flow from the subarachnoid space (SAS) across the arachnoid membrane into smaller dural vessels. Elevated CSF pressures will be achieved using constant-rate cisternal SAS infusions of artificial CSF. Outflow resistance will be determined and correlated with pressure-dependent structural changes in the outflow pathways. Sampling of blood, lymph, and CSF for radioactivity during constant-rate-infusion of radiolabelled tracers into CSF will permit quantitation of CSF transport by each outflow pathway at various CSFSSP's. Correlated light and electron microscopic studies using horseradish peroxidase, and radioiodinated albumin will be used to visualize and quantitate changes in structural barriers and permeability to CSF for each pathway when compared to pressure-induced alterations in CSF flow and outlfow resistance. The experimental induction of subarachnoid hemorrhage (SAH) will be used as a model to examine and compare the acute and long-term effects of whole blood and blood components on 1) CSF flow, 2) outlfow resistance, and 3) structure of various outflow pathways using techniques identical to those utilized in studies of the same pathways in normal animals. Thus, these correlated studies of both normal and pathologically altered outflow pathways under conditions of resting and elevated CSFSSP's, using a series of integrated physiologic and structural techniques, should provide a more comprehensive understanding of those mechanisms controlling total intracranial CSF outflow and the effect of SAH on altering the patterns of CSF absorption through pathologically altered outflow pathways.
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| Gross, P M; Sposito, N M; Pettersen, S E et al. (1986) Differences in function and structure of the capillary endothelium in the supraoptic nucleus and pituitary neural lobe of rats. Evidence for the supraoptic nucleus as an osmometer. Neuroendocrinology 44:401-7 |
