Brain edema vasogenic

Papadopoulos, M. C., Manley, G. T., Krishna, S. and Verkman, A. S. Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J. 18 1291-1293, 2004. 

Related to the post-traumatic microvascular damage is the pathophysiological process of vasogenic brain edema that represents a disruption of blood-brain barrier integrity, resulting in sodium and protein accumulation and osmotic fluid expansion of the brain extracellular space. Clinically, this is reflected by an increase in intracranial pressure which, if unchecked, can cause secondary compressive injury to vital brain structures. 

Coincident with the reduction in brain level of hydroxyl radicals, U-74006F administered at 5 minutes post-injury also acts to reduce post-traumatic opening of the blood-brain barrier (i.e. decreased brain uptake of 14C-albumin) [56]. This effect of U-74006F to close the barrier may be related to the attenuation of hydroxyl-radical levels or an antagonism of the effects of free radicals on the barrier endothelium (i.e. decreased membrane-lipid peroxidation). Indeed, free radicals are known to increase barrier permeability [57]. Consistent with this reduction in post-traumatic opening of the blood-brain barrier which would lead to vasogenic brain edema, U-74006F has been shown to attenuate post-traumatic brain edema in a rat model of fluid percussion head injury [58]. 

Hall, E.D. and Travis, M.A. (1988) Inhibition of arachidonic acid-induced vasogenic brain edema by the non-glucocorticoid 21-aminosteroid U74006F, Brain Res. 451, 350-352. 

Brain edema is defined as an abnormal accumulation of fluid associated with volumetric enlargement of the brain (Klatzo, 1967). Excess fluid can accumulate in the intracellular or extracellular spaces. Two types of brain edema have been defined based on the site of damage and where the fluid accumulates. Cytotoxic edema results in intracellular swelling without alterations in vascular permeability. Vasogenic edema is associated with damage to the BBB leading to flow of water and plasma constituents into the brain. These types of edema rarely exist in isolation typically, one type of edema dominates the other, but both co-exist. 

Experimental evidence indicates that COX modulates BBB permeability in neuroinflammatory conditions, ischemia, and hemorrhage. The COX inhibitor, KBT-3022, prevented brain edema induced by bilateral carotid occlusion and recirculation in gerbils (Yamamoto et al., 1996). In the collagenase model of intracerebral hemorrhage, the brain water content of rats treated with the COX-2 inhibitor, celecoxib, decreased both in lesioned and nonlesioned hemispheres in a dose-dependent manner, which was accompanied with reduced perihematomal cell death (Chu et al., 2004). Delayed damage to the BBB and vasogenic edema, which follow ischemic stroke, were significantly diminished by administration of... 

Chan PH, Fishman RA (1984) The role of arachidonic add in vasogenic brain edema. Fed Proc 43 210-213... 

Reulen HJ, Grahm R, Spatz M, Klatzo 1 (1977) Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J Neurosurg 46 24-34. 

Segawa, H., Patterson, R. H., 1981 Role of platelets in vasogenic brain edema. Arch. Neurol. 38, 265-270. 

Fig. 5 Aquaporin-4 deletion increases brain swelling in vasogenic edema, a Increased ICP in AQP4-null mice in response to intraparenchymal fluid infusion. Left representative ICP traces from two wildtype and AQP4 null mice. Right, increased ICP at 60 min in response to isotonic fluid infusion (0.5 p.l/min). Data shown for individual mice and mean SE. b Increased ICP and in AQP4 null mice with melanoma brain tumor. Top, site of injection of melanoma cells. Bottom., tumor size at 4 and 7 days after implantation showing similar-sized tumors in wildtype and AQP4 null mice, c ICP measured 7 days after tumor implantation. From Papadopoulos et al. (2004)...

MRI Changes Corresponding to Vasogenic Edema after Experimental Brain Ischemia 137... 

MRI can provide valuable information on the progression of vasogenic edema and necrosis in the living organism. Free and bound water (e.g., water in the ventricles vs. water bound to cellular structures) can be discriminated based on different T1 and T2 relaxation times (Bakay et al. 1975 Naruse et al. 1982). Typical T1 and T2 relaxation times of normal rat brain at 4.7 T are 869+145 ms and 72+2 ms (caudate putamen) and 928 117 ms and 73 2 ms (cortex), while more liquid structures such as edematous tissue, cysts or CSF will lead to significantly elevated T1 and T2 relaxation times (Hoehn-Berlage et al. 1995). 

---