Novel Treatment Targets for Cerebral Edema

Elsevier BV - Tập 9 - Trang 65-72 - 2011
Brian P. Walcott1, Kristopher T. Kahle1, J. Marc Simard2
1Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
2Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, USA

Tóm tắt

Cerebral edema is a common finding in a variety of neurological conditions, including ischemic stroke, traumatic brain injury, ruptured cerebral aneurysm, and neoplasia. With the possible exception of neoplasia, most pathological processes leading to edema seem to share similar molecular mechanisms of edema formation. Challenges to brain-cell volume homeostasis can have dramatic consequences, given the fixed volume of the rigid skull and the effect of swelling on secondary neuronal injury. With even small changes in cellular and extracellular volume, cerebral edema can compromise regional or global cerebral blood flow and metabolism or result in compression of vital brain structures. Osmotherapy has been the mainstay of pharmacologic therapy and is typically administered as part of an escalating medical treatment algorithm that can include corticosteroids, diuretics, and pharmacological cerebral metabolic suppression. Novel treatment targets for cerebral edema include the Na(+)-K(+)-2Cl(−) co-transporter (NKCC1) and the SUR1-regulated NCCa-ATP (SUR1/TRPM4) channel. These two ion channels have been demonstrated to be critical mediators of edema formation in brain-injured states. Their specific inhibitors, bumetanide and glibenclamide, respectively, are well-characterized Food and Drug Administration-approved drugs with excellent safety profiles. Directed inhibition of these ion transporters has the potential to reduce the development of cerebral edema and is currently being investigated in human clinical trials. Another class of treatment agents for cerebral edema is vasopressin receptor antagonists. Euvolemic hyponatremia is present in a myriad of neurological conditions resulting in cerebral edema. A specific antagonist of the vasopressin V1A- and V2-receptor, conivaptan, promotes water excretion while sparing electrolytes through a process known as aquaresis.

Tài liệu tham khảo

Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med 2001;344:264–269. Matsuzaki M, Takahashi R, Nakayama T, et al. Disruption of endothelial tight junctions in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Neuropediatrics 2010;41:72–74. Kahle KT, Walcott BP, Nahed BV, et al. Cerebral edema and a transtentorial brain herniation syndrome associated with pandemic swine influenza A (H1N1) virus infection. J Clin Neurosci 2011;18:1245–1248. Gerstner ER, Duda DG, di Tomaso E, et al. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol 2009;6:229–236. Hofmeijer J, Algra A, Kappelle LJ, van der Worp HB. Predictors of life-threatening brain edema in middle cerebral artery infarction. Cerebrovasc Dis 2008;25:176–184. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol 2009;8:326–333. Simard JM, Sahuquillo J, Sheth KN, Kahle KT, Walcott BP. Managing malignant cerebral infarction. Curr Treat Options Neurol 2011;13:217–229. Wilde EA, McCauley SR, Hunter JV, et al. Diffusion tensor imaging of acute mild traumatic brain injury in adolescents. Neurology 2008;70:948–955. Donkin JJ, Vink R. Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol 2010;23:293–299. Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol 2007;6:258–268. Unterberg AW, Stover J, Kress B, Kiening KL. Edema and brain trauma. Neuroscience 2004;129:1021–1029. King LS, Agre P. Pathophysiology of the aquaporin water channels. Annu Rev Physiol 1996;58:619–648. Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat. Med 2000;6:159–163. Badaut J, Lasbennes F, Magistretti PJ, Regli L. Aquaporins in brain: distribution, physiology, and pathophysiology. J Cereb Blood Flow Metab 2002;22:367–378. Amiry-Moghaddam M, Ottersen OP. The molecular basis of water transport in the brain. Nat Rev Neurosci 2003;4:991–1001. Ribeiro MDC, Hirt L, Bogousslavsky J, Regli L, Badaut J. Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res 2006;83:1231–1240. Banasiak KJ, Burenkova O, Haddad GG. Activation of voltage-sensitive sodium channels during oxygen deprivation leads to apoptotic neuronal death. Neuroscience 2004;126:31–44. Beck J, Lenart B, Kintner DB, Sun D. Na-K-Cl Cotransporter Contributes to Glutamate-Mediated Excitotoxicity. J Neurosci 2003;23:5061–5068. Breder J, Sabelhaus CF, Opitz T, Reymann KG, Schröder UH. Inhibition of different pathways influencing Na + homeostasis protects organotypic hippocampal slice cultures from hypoxic/hypoglycemic injury. Neuropharmacology 2000;39:1779–1787. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. "Malignant" middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 1996;53:309–315. 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;100:376–383. Chesnut RM, Gautille T, Blunt BA, Klauber MR, Marshall LF. Neurogenic hypotension in patients with severe head injuries. J Trauma 1998;44:958–964. Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg 1992;77:584–589. Ware ML, Nemani VM, Meeker M, Lee C, Morabito DJ, Manley GT. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery 2005;57:727–736. Kerwin AJ, Schinco MA, Tepas JJ 3rd, Renfro WH, Vitarbo EA, Muehlberger M. The use of 23.4% hypertonic saline for the management of elevated intracranial pressure in patients with severe traumatic brain injury: a pilot study. J Trauma 2009;67:277–282. Weed LH, McKibben PS. Experimental alteration of brain bulk. Am J Physiol 1919;48:531–558. Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000;28:3301–3313. Koenig MA, Bryan M, Lewin JL, Mirski MA, Geocadin RG, Stevens RD. Reversal of transtentorial herniation with hypertonic saline. Neurology 2008;70:1023–1029. Zeynalov E, Chen C, Froehner SC, et al. The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema. Crit Care Med 2008;36:2634–2640. Gundersen Y, Ruud TE, Krohn CD, Sveen O, Lyngstadaas SP, Aasen AO. Impact of hypertonic saline on the release of selected cytokines after stimulation with LPS or peptidoglycan in ex vivo whole blood from healthy humans. Shock 2010;34:450–454. Jin QH, Ueda Y, Ishizuka Y, Kunitake T, Kannan H. Cardiovascular changes induced by central hypertonic saline are accompanied by glutamate release in awake rats. Am J Physiol Regul Integr Comp Physiol 2001;281:R1224-R1231. Chodobski A. Possible new mechanism underlying hypertonic saline therapy for cerebral edema. J Appl Physiol 2006;100:1437–1438. Qureshi AI, Wilson DA, Traystman RJ. Treatment of transtentorial herniation unresponsive to hyperventilation using hypertonic saline in dogs: effect on cerebral blood flow and metabolism. J Neurosurg Anesthesiol 2002;14:22–30. Qureshi AI, Suri MFK, Ringer AJ, Guterman LR, Hopkins LN. Regional intraparenchymal pressure differences in experimental intracerebral hemorrhage: effect of hypertonic saline. Crit Care Med 2002;30:435–441. Toung TJ, Nyquist P, Mirski MA. Effect of hypertonic saline concentration on cerebral and visceral organ water in an uninjured rodent model. Crit Care Med 2008;36:256–261. Qureshi AI, Wilson DA, Traystman RJ. Treatment of elevated intracranial pressure in experimental intracerebral hemorrhage: comparison between mannitol and hypertonic saline. Neurosurgery 1999;44:1055–1064. Suarez JI, Qureshi AI, Bhardwaj A, et al. Treatment of refractory intracranial hypertension with 23.4% saline. Crit Care Med 1998;26:1118–1122. Rockswold GL, Solid CA, Paredes-Andrade E, Rockswold SB, Jancik JT, Quickel RR. Hypertonic saline and its effect on intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen. Neurosurgery 2009;65:1035–1042. Delashaw JB, Broaddus WC, Kassell NF, Haley EC, Pendleton GA, Vollmer DG, et al. Treatment of right hemispheric cerebral infarction by hemicraniectomy. Stroke 1990;21:874–881. Schwab S, Steiner T, Aschoff A, et al. Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke 1998;29:1888–1893. Fisher CM, Ojemann RG. Bilateral decompressive craniectomy for worsening coma in acute subarachnoid hemorrhage. Observations in support of the procedure. Surg Neurol 1994;41:65–74. Carter BS, Ogilvy CS, Candia GJ, Rosas HD, Buonanno F. One-year outcome after decompressive surgery for massive nondominant hemispheric infarction. Neurosurgery 1997;40:1168–1176. Uhl E, Kreth FW, Elias B, et al. Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction. J Neurol Neurosurg Psychiatr 2004;75:270–274. Jüttler E, Schwab S, Schmiedek P, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke 2007;38:2518–2525. Vahedi K, Vicaut E, Mateo J, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke 2007;38:2506–2517. Frank J. Hemicraniectomy and durotomy upon deterioration from infarction related swelling trial (HeADDFIRST): first public presentation of the primary study findings. Neurology 2003;(60 suppl 1):A426. Walberer M, Ritschel N, Nedelmann M, et al. Aggravation of infarct formation by brain swelling in a large territorial stroke: a target for neuroprotection? J Neurosurg 2008;109:287–293. Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 2011;364:1493–1502. Smith DS, Rehncrona S, Siesjö BK. Barbiturates as protective agents in brain ischemia and as free radical scavengers in vitro. Acta Physiol Scand Suppl 1980;492:129–134. Qizilbash N, Lewington SL, Lopez-Arrieta JM. Corticosteroids for acute ischaemic stroke. Cochrane Database Syst Rev 2002;(2):CD000064. Betz AL, Iannotti F, Hoff JT. Brain edema: a classification based on blood–brain barrier integrity. Cerebrovasc Brain Metab Rev 1989;1:133–154 Young W, Rappaport Z, Chalif D, Flamm E. Regional brain sodium, potassium, and water changes in the rat middle cerebral artery occlusion model of ischemia. Stroke 1987;18:751–759. Kahle KT, Staley KJ, Nahed BV, et al. Roles of the cation-chloride cotransporters in neurological disease. Nat Clin Pract Neurol 2008;4:490–503. Yan Y, Dempsey RJ, Sun D. Na + −K + −Cl- cotransporter in rat focal cerebral ischemia. J Cereb Blood Flow Metab 2001;21:711–721. Yan Y, Dempsey RJ, Flemmer A, Forbush B, Sun D. Inhibition of Na(+)-K(+)-Cl(−) cotransporter during focal cerebral ischemia decreases edema and neuronal damage. Brain Res 2003;961:22–31. Su G, Kintner DB, Flagella M, Shull GE, Sun D. Astrocytes from Na + −K + −Cl − cotransporter-null mice exhibit absence of swelling and decrease in EAA release. American J Physiol Cell Physiol 2002;282:C1147-C1160. Su G, Kintner DB, Sun D. Contribution of Na + −K + −Cl − cotransporter to high-[K+]o- induced swelling and EAA release in astrocytes. Am J Physiol Cell Physiol 2002;282:C1136-C1146. Chen H, Sun D. The role of Na-K-Cl co-transporter in cerebral ischemia. Neurol Res 2005;27:280–286. Staley KJ. Wrong-way chloride transport: is it a treatable cause of some intractable seizures? Epilepsy Curr 2006;6:124–127. Maa EH, Kahle KT, Walcott BP, Spitz MC, Staley KJ. Diuretics and epilepsy: will the past and present meet? Epilepsia 2011;52(9):1559–1569. Lu K, Cheng N, Wu C, Yang Y. NKCC1-mediated traumatic brain injury-induced brain edema and neuron death via Raf/MEK/MAPK cascade. Crit Care Med 2008;36:917–922. Lu K, Wu C, Yen H, Peng JF, Wang C, Yang Y. Bumetanide administration attenuated traumatic brain injury through IL-1 overexpression. Neurol Res 2007;29:404–409. Lu K, Wu C, Cheng N, et al. Inhibition of the Na + −K + −2Cl- cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage. Eur J Pharmacol 2006;548:99–105. 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. Simard JM, Chen M, Tarasov KV, et al. Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke. Nat Med 2006;12:433–440. Simard JM, Kahle KT, Gerzanich V. Molecular mechanisms of microvascular failure in central nervous system injury — synergistic roles of NKCC1 and SUR1/TRPM4. J Neurosurg 2010;113:622–629. Conti L, Palma E, Roseti C, et al. Anomalous levels of Cl- transporters cause a decrease of GABAergic inhibition in human peritumoral epileptic cortex. Epilepsia 2011;52:1635–1644. Haas BR, Sontheimer H. Inhibition of the sodium-potassium-chloride cotransporter isoform-1 reduces glioma invasion. Cancer Res 2010;70:5597–5606. Seino S. ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies. Annu Rev Physiol 1999;61:337–362. Chang Y, Chen T, Chen C, Crain BJ, Toung TJK, Bhardwaj A. Plasma arginine-vasopressin following experimental stroke: effect of osmotherapy. J Appl Physiol 2006;100:1445–1451. 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;21:6512–6521. Chen M, Dong Y, Simard JM. Functional coupling between sulfonylurea receptor type 1 and a nonselective cation channel in reactive astrocytes from adult rat brain. J Neurosci 2003;23:8568–8577. Ningaraj NS, Rao MK, Black KL. Adenosine 5'-triphosphate-sensitive potassium channel-mediated blood–brain tumor barrier permeability increase in a rat brain tumor model. Cancer Res 2003;63:8899–8911. Zhang H, Gu YT, Xue YX. Bradykinin-induced blood–brain tumor barrier permeability increase is mediated by adenosine 5'-triphosphate-sensitive potassium channel. Brain Res 2007;1144:33–41. 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;41:531–537. Wijdicks EF, Ropper AH, Hunnicutt EJ, Richardson GS, Nathanson JA. Atrial natriuretic factor and salt wasting after aneurysmal subarachnoid hemorrhage. Stroke 1991;22:1519–1524. Sherlock M, O'Sullivan E, Agha A, et al. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf) 2006;64:250–254. Wartenberg KE, Schmidt JM, Claassen J, et al. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med 2006;34:617–624. Hasan D, Wijdicks EF, Vermeulen M. Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol 1990;27:106–108. Soupart A, Decaux G. Therapeutic recommendations for management of severe hyponatremia: current concepts on pathogenesis and prevention of neurologic complications. Clin Nephrol 1996;46:149–169. Upadhyay UM, Gormley WB. Etiology and management of hyponatremia in neurosurgical patients. J Intensive Care Med 2011;Feb 23 [online]:PMID 21345881. Diringer MN, Zazulia AR. Hyponatremia in neurologic patients: consequences and approaches to treatment. Neurologist 2006;12:117–126. Rahman M, Friedman WA. Hyponatremia in neurosurgical patients: clinical guidelines development. Neurosurgery 2009;65:925–936. Origitano TC, Wascher TM, Reichman OH, Anderson DE. Sustained increased cerebral blood flow with prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) after subarachnoid hemorrhage. Neurosurgery 1990;27:729–740. Wijdicks EF, Vermeulen M, Hijdra A, van Gijn J. Hyponatremia and cerebral infarction in patients with ruptured intracranial aneurysms: is fluid restriction harmful? Ann Neurol 1985;17:137–140. Woo MH, Kale-Pradhan PB. Fludrocortisone in the treatment of subarachnoid hemorrhage-induced hyponatremia. Ann Pharmacother 1997;31:637–639. Wijdicks EF, Vermeulen M, van Brummelen P, van Gijn J. The effect of fludrocortisone acetate on plasma volume and natriuresis in patients with aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg 1988;90:209–214. Cawley MJ. Hyponatremia: current treatment strategies and the role of vasopressin antagonists. Ann Pharmacother 2007;41:840–850. Hays RM. Vasopressin antagonists — progress and promise. N Engl J Med 2006;355:2146–2148. Palm C, Pistrosch F, Herbrig K, Gross P. Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med 2006;119(7 suppl 1):S87-S92. Decaux G, Soupart A, Vassart G. Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet 2008;371:1624–1632. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 2007;27:447–457. Yeates KE, Morton AR. Vasopressin antagonists: role in the management of hyponatremia. Am J Nephrol 2006;26:348–355. Ghali JK, Koren MJ, Taylor JR, et al. Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab 2006;91:2145–2152. Murphy T, Dhar R, Diringer M. Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care 2009;11:14–19. Wright WL, Asbury WH, Gilmore JL, Samuels OB. Conivaptan for hyponatremia in the neurocritical care unit. Neurocrit Care 2009;11:6–13. László FA, Varga C, Dóczi T. Cerebral oedema after subarachnoid haemorrhage. Pathogenetic significance of vasopressin. Acta Neurochir (Wien) 1995;133:122–133. Dhar R, Murphy-Human T. A bolus of conivaptan lowers intracranial pressure in a patient with hyponatremia after traumatic brain injury. Neurocrit Care 2011;14:97–102. 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;14:354–360.