Biomechanics of brain edema and effects on local cerebral blood flow.

Brain edema represents a disturbance of the volume equilibrium which, in the early stages of formation, must be compensated for by a reduction in other fluid and blood compartments. When this compensation is inadequate, tissue pressure and intracranial pressure increase, the magnitude of which depends on the compliance of the tissue. Tissue pressure gradients develop within the same hemisphere and between hemispheres, but these pressure gradients are transient and dissipate within a few hours after injury. The rate of dissipation is proportional to the product of hydraulic tissue resistance and compliance. These tissue pressure gradients are small in magnitude, less than 15 mm Hg; however, studies with an infusion model of edema in animals show that they are more than sufficient to propel fluid through the parenchyma by a process of bulk flow. The distention caused by the fluid increases the conductance and compliance of the tissue. This biomechanical response favors the dissipation of pressure gradients, and as a result hydrostatic gradients can be sustained only with a continued leakage of fluid from the site of injury. Without a continued extravasation of fluid, equilibration of the tissue pressure to the level of the ICP occurs rapidly. For this reason, the role of hydrostatic gradients in the resorption process may be limited. The development of an infusion model allows more rigid control and simulates the edematous process. Ultrastructural studies of the infusion model have shown that the tissue changes are similar to those reported for vasogenic edema, with the exception that in the infusion model the blood-brain barrier remains intact in the vicinity of the lesion and is not compromised by the mechanical distention of the ECS. The response of the cerebrovasculature to the infusion edema is in contrast to the usual reduction of flow seen after cryogenic injury. The CBF remains constant despite increased tissue water, as confirmed by gravimetric technique. The CO2 reactivity of the vessels in the area of edema is reduced, but the autoregulation to changes in perfusion pressure remains intact. When arterial pressure is raised beyond the limit of autoregulation, the pressure increase of CBF in the edematous area is less than the rise of CBF in normal tissue and suggests a "false autoregulation" caused by an increased tissue pressure. The differences in both the intracranial pressure and CBF response between these two models suggests that other factors must be operative. The cryogenic injury is indeed a traumatic injury to the brain and cannot be simply characterized by the increase in brain tissue water. In some animals a vasomotor paralysis disrupting the vascular compartmental volume and leading to a rapid rise in ICP with eventual reduction of CPP and CBF may explain these differences. Release of vasoactive substances into the ECS is an exciting hypothesis and is an area of investigation ideally suited to the infusion edema process where chemical composition of the fluid can be easily controlled.