Cerebral oedema: Pathophysiological mechanisms and experimental therapies

INTRODUCTION

Cerebral oedema per se is not a disease entity. It is a clinico-pathological state that is characterised by an increase in brain water content (above the normal brain water content of approximately 80%). It usually occurs in response to brain insult which is seen in a variety of neurological and non-neurological conditions. Cerebral oedema increases brain volume. Because brain is confined within rigid skull, increase in brain water content ultimately results in raised intracranial pressure (ICP). Raised ICP decreases cerebral perfusion pressure leading to cerebral ischemia. In addition, cerebral oedema may result in brain herniation due to the associated mass effect. Management of cerebral oedema is a great challenge for both the neurosurgeons and neuroanaesthetists as current treatment modalities are largely symptomatic. They range from general measures to osmotherapy, barbiturate coma, steroids and decompressive craniectomy. Though oedema-targeted therapies are being specifically designed, they remain more or less as experimental models.

• REFERENCES

• 1 Reichardt M. Zur entstehung des hirndrucks. Deutsch Z Nervenheilkd 1905; 28: 306
• 2 Klatzo I. Presidental address. Neuropathological aspects of brain edema. J Neuropathol Exp Neurol 1967; 26: 1-14
• 3 Fishman RA. Brain edema. N Engl J Med 1975; 293: 706-11
• 4 Møllgård K, Saunders NR. The development of the human blood-brain and blood-CSF barriers. Neuropathol Appl Neurobiol 1986; 12: 337-58
• 5 Betz AL, Iannotti F, Hoff JT. Brain edema: A classification based on blood-brain barrier integrity. Cerebrovasc Brain Metab Rev 1989; 1: 133-54
• 6 Kuroiwa T, Miyasaka N, Fengyo Z, Yamada I, Nakane M, Nagaoka T. et al. Experimental ischemic brain edema: Morphological and magnetic resonance imaging findings. Neurosurg Focus 2007; 22: E11
• 7 Wasterlain CG, Posner JB. Cerebral edema in water intoxication. I. Clinical and chemical observations. Arch Neurol 1968; 19: 71-8
• 8 Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci 2004; 61: 657-68
• 9 Barron KD, Dentinger MP, Kimelberg HK, Nelson LR, Bourke RS, Keegan S. et al. Ultrastructural features of a brain injury model in cat. I. Vascular and neuroglial changes and the prevention of astroglial swelling by a fluorenyl (aryloxy) alkanoic acid derivative (L-644,711). Acta Neuropathol 1988; 75: 295-307
• 10 Kimelberg HK. Current concepts of brain edema. Review of laboratory investigations. J Neurosurg 1995; 83: 1051-9
• 11 Milhorat TH, Clark RG, Hammock MK. Experimental hydrocephalus. 2. Gross pathological findings in acute and subacute obstructive hydrocephalus in the dog and monkey. J Neurosurg 1970; 32: 390-9
• 12 Milhorat TH, Clark RG, Hammock MK, McGrath PP. Structural, ultrastructural, and permeability changes in the ependyma and surrounding brain favoring equilibration in progressive hydrocephalus. Arch Neurol 1970; 22: 397-407
• 13 Katayama Y, Kawamata T. Edema fluid accumulation within necrotic brain tissue as a cause of the mass effect of cerebral contusion in head trauma patients. Acta Neurochir Suppl 2003; 86: 323-7
• 14 Mokri B. The Monro-Kellie hypothesis: Applications in CSF volume depletion. Neurology 2001; 56: 1746-8
• 15 Loubinoux I, Volk A, Borredon J, Guirimand S, Tiffon B, Seylaz J. et al. Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke 1997; 28: 419-26
• 16 Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: A randomized trial. J Neurosurg 2004; 100: 376-83
• 17 Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000; 28: 3301-13
• 18 Plotkin MD, Kaplan MR, Peterson LN, Gullan SR, Hebert SC, Delpire E. Expression of the Na-K-2Cl co transporter BSC2 in the nervous system. Am J Physiol 1997; 272: C173-83
• 19 Payne JA, Xu JC, Haas M, Lytle CY, Ward D, Forbush 3^rd B. Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon. J Biol Chem 1995; 270: 17977-85
• 20 Asbury MJ, Gatenby PB, O'Sullivan S, Bourke E. Bumetanide: Potent new “loop” diuretic. Br Med J 1972; 1: 211-3
• 21 Staley KJ. Wrong-way chloride transport: Is it a treatable cause of some intractable seizures?. Epilepsy Curr 2006; 6: 124-7
• 22 Haas BR, Sontheimer H. Inhibition of the sodium-potassium-chloride cotransporter isoform-1 reduces glioma invasion. Cancer Res 2010; 70: 5597-606
• 23 Lu KT, Wu CY, Yen HH, Peng JH, Wang CL, Yang YL. Bumetanide administration attenuated traumatic brain injury through IL-1 overexpression. Neurol Res 2007; 29: 404-9
• 24 Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L. et al. Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke. Nat Med 2006; 12: 433-40
• 25 Chen H, Luo J, Kintner DB, Shull GE, Sun D. Na(+)-dependent chloride transporter (NKCC1)-null mice exhibit less gray and white matter damage after focal cerebral ischemia. J Cereb Blood Flow Metab 2005; 25: 54-66
• 26 Staub F, Stoffel M, Berger S, Eriskat J, Baethmann A. Treatment of vasogenic brain edema with the novel Cl- transport inhibitor torasemide. J Neurotrauma 1994; 11: 679-90
• 27 Chen M, Simard JM. Cell swelling and a nonselective cation channel regulated by internal Ca2+ and ATP in native reactive astrocytes from adult rat brain. J Neurosci 2001; 21: 6512-21
• 28 Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V. Sulfonylurea receptor 1 in central nervous system injury: A focused review. J Cereb Blood Flow Metab 2012; 32: 1699-717
• 29 Zweckberger K, Hackenberg K, Jung CS, Hertle DN, Kiening KL, Unterberg AW. et al. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury. Neuroscience 2014; 272: 199-206
• 30 Simard JM, Tsymbalyuk N, Tsymbalyuk O, Ivanova S, Yurovsky V, Gerzanich V. Glibenclamide is superior to decompressive craniectomy in a rat model of malignant stroke. Stroke 2010; 41: 531-7
• 31 Sherlock M, O'Sullivan E, Agha A, Behan LA, Rawluk D, Brennan P. et al. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf) 2006; 64: 250-4
• 32 Cawley MJ. Hyponatremia: Current treatment strategies and the role of vasopressin antagonists. Ann Pharmacother 2007; 41: 840-50
• 33 Palm C, Pistrosch F, Herbrig K, Gross P. Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med 2006; 119 (07) Suppl (Suppl. 01) S87-92
• 34 Murphy T, Dhar R, Diringer M. Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care 2009; 11: 14-9
• 35 Wright WL, Asbury WH, Gilmore JL, Samuels OB. Conivaptan for hyponatremia in the neurocritical care unit. Neurocrit Care 2009; 11: 6-13
• 36 Galton C, Deem S, Yanez ND, Souter M, Chesnut R, Dagal A. et al. Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury. Neurocrit Care 2011; 14: 354-60
• 37 Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system. Nat Rev Neurosci 2013; 14: 265-77
• 38 Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol 2007; 22: 778-84
• 39 Yang B, Zador Z, Verkman AS. Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem 2008; 283: 15280-6
• 40 Papadopoulos MC, Manley GT, Krishna S, Verkman AS. Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 2004; 18: 1291-3
• 41 Igarashi H, Huber VJ, Tsujita M, Nakada T. Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema. Neurol Sci 2011; 32: 113-6
• 42 Bhattacharya P, Pandey AK, Paul S, Patnaik R, Yavagal DR. Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rodents. PLoS One 2013; 8: e73481
• 43 Shigemori Y, Katayama Y, Mori T, Maeda T, Kawamata T. Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats. Acta Neurochir Suppl 2006; 96: 130-3
• 44 Sood RR, Taheri S, Candelario-Jalil E, Estrada EY, Rosenberg GA. Early beneficial effect of matrix metalloproteinase inhibition on blood-brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain. J Cereb Blood Flow Metab 2008; 28: 431-8
• 45 Jiang S, Xia R, Jiang Y, Wang L, Gao F. Vascular endothelial growth factors enhance the permeability of the mouse blood-brain barrier. PLoS One 2014; 9: e86407
• 46 Koyama J, Miyake S, Sasayama T, Kondoh T, Kohmura E. Effect of VEGF receptor antagonist (VGA1155) on brain edema in the rat cold injury model. Kobe J Med Sci 2007; 53: 199-207
• 47 Koyama Y, Tanaka K. Intracerebroventricular administration of an endothelin ETB-receptor agonist increases expression of matrix metalloproteinase-2 and -9 in rat brain. J Pharmacol Sci 2010; 114: 433-43
• 48 Koyama Y, Nagae R, Tokuyama S, Tanaka K. I.c.v. administration of an endothelin ETB receptor agonist stimulates vascular endothelial growth factor – A production and activates vascular endothelial growth factor receptors in rat brain. Neuroscience 2011; 192: 689-98
• 49 Michinaga S, Nagase M, Matsuyama E, Yamanaka D, Seno N, Fuka M. et al. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice. PLoS One 2014; 9: e102009