Brain edema proteins

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. 

Fig. 9.5 Decreased expression of EAAT-2 in brain in experimental ALF. Decreased EAAT-2 mRNA (panel A) and EAAT-2 protein (panel B) in rats with ALF resulting from hepatic devascu-larization (portacaval anastomosis followed by hepatic artery ligation). Rats had severe HE and brain edema. Panel C shows decreased uptake of the glutamate analogue H-D-Aspartate by cortical shces from ALF tats (Data from Knecht et al., 1997)...

The encephalopathy induced by lead toxicity is most hkely due to a compromise in the blood-brain barrier. Brain edema occurs in the interstitial area and appears due to compromised blood vessels integrity. The brain capillaries and blood vessels have endothelial cells that contain tight junctions and act as a seal or carrier that excludes many plasma proteins and organic molecules and impedes Na and K exchange. Elevated lead levels disrupt these vessels, and plasma proteins such as albumin enter the interstitial spaces, as do some ions. This increases osmotic pressure, and water accumulates in response. The increased interstitial fluid flows into the cerebrospinal fluid. The edema causes in an increase in intracranial pressure and restricts blood flow to the brain. The direct mechanisms by which the blood-brain barrier and blood vessels that compose the barrier may be compromised may be due to astrocytes appearing to be vulnerable to the toxic effects of lead. The astrocytes cover the walls of the brain blood vessels, and lead can injure these structures. 

With disruption of this barrier, molecules such as albumin freely enter the brain and ions and water follow. Because the brain lacks a well-developed lymphatic system, clearance of plasma constituents is slow, edema occurs, and intracranial pressure rises. At lower levels of exposure, subtle dysfunction of the blood-brain barrier may contribute to neurobehavioral deficits in children (Bressler and Goldstein 1991 Goldstein 1993). The particular vulnerability of the fetus and infant to the neurotoxicity of lead may be due in part to immaturity of the blood-brain barrier and to the lack of the high-affinity leadbinding protein in astroglia, which is discussed later in this section. Results of measurements of transendothelial electrical resistance across the blood-brain barrier from mice of various ages showed that lead potentiates cytokines-induced increase in ion permeability of the blood-brain barrier (Dyatlov et al. 

---