Astrocytes brain edema

A number of toxic conditions beside hypoosmotic stress and hypoxia/ischemia produce brain edema and the causes may be related to regulation of the aquaporins (see Ch. 34). AQP1 and AQP4 are intensely upregulated in reactive astrocytes in subarachnoid hemorrhage [69], in human glioma and astrocytoma [70] and AQP4 in endothelia and reactive astrocytes in metastatic carcinoma [71,72]. 

Amiry-Moghaddam M, Xue R, Haug FM, Neely JD, Bhardwaj A, Agre P, Adams ME, Froehner SC, Mori S, Ottersen OP (2004) Alpha-syntrophin deletion removes the perivascular but not endotheUeil pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimenUil model of acute hyponatremia. FASEB J 18 542-544 Anderson CM, Nedeigaard M (2003) Astrocyte-mediated control of cerebral microcirculation. Trends Neurosci 26 340-345... 

Kaur C, Sivakumar V, Zhang Y, ling EA (2(X)6) Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum. Gha 54 826-839 Kim JH, Park JA, Lee SW, Kim WJ, Yu YS, Kim KW (2006) Blood-neural barrier intercellular communication at gUo-vascular interface. J Biochem Mol Biol 39 339-345 Kimelberg HK (1995) Current concepts of brain edema. Review of laboratory investigations. J Neurosurg 83 1051-1059... 

KlatzD 1 (1994) Evolution of brain edema concepts. Acta Neurochir Suppl (Wien) 60 3-6 Koehler RC, Roman RJ, Harder DR (2009) Astrocytes and the regulation of cerebral blood flow. Trends Neurosd 32 160-169... 

Lo AC, Chen AY, Hung VK, Yaw LP, Fung MK, Ho MC, Tsang MC, Chung SS, Chung SK (2005) Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet. J Cereb Blood Flow Metab 25 998-1011... 

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. 

Aquoporins are water channels that mediate rapid osmotically driven water transport across ceU membranes (Preston et al., 1992 Agre et al., 2002 Badaut et al., 2002). Brain tissues, including microvessels, contain relatively high levels of aquaporins. In particular, Aquaporin 4 (AQP4) is abundantly expressed in the brain, mainly in astrocytes, which are commonly observed to be swollen during cerebral edema (Jung et al., 1994 Kimelberg, 1995 Nielsen et al., 1997). 

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