Abstract
The prominent role of inflammatory pathways in acute brain injury has become increasingly clear in recent literature. The complement system represents a heterogeneous group of inflammatory molecules capable of being activated by numerous stimuli to a large number of ends. In this chapter, we review the mechanisms of the complement system, with emphasis on C5 and C3. We then present the leading theories of the conflicting role of the complement system in central nervous system disease and the current state of investigations attempting to modify injury through modulation of the complement system.
Keywords
- Ischemic Stroke
- Cerebral Amyloid Angiopathy
- Central Nervous System Disease
- Membrane Attack Complex
- Complement Cascade
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Miniño AM, et al (2011) Deaths: final data for 2008. In: National Vital Statistics Report. Center for Disease Control and Prevention
Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22(9):391–7
Heidenreich PA et al (2011) Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation 123(8):933–44
National Heart, Lung, and Blood Institute (2006) Incidence and prevalence: 2006 chart book on cardiovascular and lung diseases. National Institute of Health: National Heart, Lung, and Blood Institute, Bethesda, MD
Roger VL et al (2011) Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 123(4):e18–209
Bazarian JJ et al (2005) Mild traumatic brain injury in the United States, 1998–2000. Brain Inj 19(2):85–91
Carroll LJ et al (2004) Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on mild traumatic brain injury. J Rehabil Med 2004(43 Suppl):84–105
Walport MJ (2001) Complement. First of two parts. N Engl J Med 344(14):1058–66
Cole DS, Morgan BP (2003) Beyond lysis: how complement influences cell fate. Clin Sci (Lond) 104(5):455–66
Peitsch MC, Tschopp J (1991) Assembly of macromolecular pores by immune defense systems. Curr Opin Cell Biol 3(4):710–6
Lee A, Whyte MK, Haslett C (1993) Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 54(4):283–8
Riedemann NC et al (2002) C5a receptor and thymocyte apoptosis in sepsis. FASEB J 16(8):887–8
Takabayashi T et al (1996) A new biologic role for C3a and C3a desArg: regulation of TNF-alpha and IL-1 beta synthesis. J Immunol 156(9):3455–60
Davis AE 3rd (2004) Biological effects of C1 inhibitor. Drug News Perspect 17(7):439–46
Lampl L et al (1994) Blood coagulation parameters as prognostic factors in multiple trauma: can clinical values be an early diagnostic aid? Zentralbl Chir 119(10):683–9
Lidington EA, Haskard DO, Mason JC (2000) Induction of decay-accelerating factor by thrombin through a protease-activated receptor 1 and protein kinase C-dependent pathway protects vascular endothelial cells from complement-mediated injury. Blood 96(8):2784–92
Ganter MT et al (2007) Role of the alternative pathway in the early complement activation following major trauma. Shock 28(1):29–34
Amara U et al (2008) Interaction between the coagulation and complement system. Adv Exp Med Biol 632:71–9
Huber-Lang M et al (2006) Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 12(6):682–7
Hankey GJ, Norman PE, Eikelboom JW (2006) Medical treatment of peripheral arterial disease. JAMA 295(5):547–53
Deb P, Sharma S, Hassan KM (2010) Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology 17(3):197–218
Mocco J et al (2006) The complement system: a potential target for stroke therapy. Adv Exp Med Biol 586:189–201
Feuerstein GZ, Wang X, Barone FC (1998) Cerebrovascular disease: pathophysiology, diagnosis, and management. In: Ginsberg MD, Bogousslavsky J (eds), Blackwell, Malden, MA
Belayev L et al (1996) Quantitative evaluation of blood–brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739(1–2):88–96
Klatzo I (1987) Pathophysiological aspects of brain edema. Acta Neuropathol 72(3):236–9
Fishman RA (1992) Cerebrospinal fluid in diseases of the nervous system, 2nd edn. Saunders, Philadelphia, p 431
Adams HP Jr et al (2007) Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 38(5):1655–711
Lees KR et al (2010) Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375(9727):1695–703
Fujii Y et al (1994) Hematoma enlargement in spontaneous intracerebral hemorrhage. J Neurosurg 80(1):51–7
Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 5(1):53–63
Broderick JP et al (1990) Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg 72(2):195–9
Zazulia AR et al (1999) Progression of mass effect after intracerebral hemorrhage. Stroke 30(6):1167–73
Xi G et al (2001) Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke 32(1):162–7
Hua Y et al (2000) Complement activation in the brain after experimental intracerebral hemorrhage. J Neurosurg 92(6):1016–22
Hua Y et al (1999) Complement C9 accumulation, membrane attack complex (MAC) formation and cluster in up regulation following intracerebral hemorrhage. J Cereb Blood Flow Metab 19(suppl 1):S670
Zhang X et al (2006) Brain edema after intracerebral hemorrhage in rats: the role of inflammation. Neurol India 54(4):402–7
Broderick JP et al (1993) Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 24(7):987–93
Broderick J et al (2007) Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation 116(16):e391–413
Ropper AH (1986) Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. N Engl J Med 314(15):953–8
Ropper AH, King RB (1984) Intracranial pressure monitoring in comatose patients with cerebral hemorrhage. Arch Neurol 41(7):725–8
Morgenstern LB et al (2010) Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 41(9):2108–29
Sughrue ME et al (2004) Anti-adhesion molecule strategies as potential neuroprotective agents in cerebral ischemia: a critical review of the literature. Inflamm Res 53(10):497–508
Schafer MK et al (2000) Complement C1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia. J Immunol 164(10):5446–52
Cowell RM, Plane JM, Silverstein FS (2003) Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats. J Neurosci 23(28):9459–68
Huang J et al (1999) Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science 285(5427):595–9
Rahpeymai Y et al (2006) Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J 25(6):1364–74
Gasque P et al (2000) Complement components of the innate immune system in health and disease in the CNS. Immunopharmacology 49(1–2):171–86
Nataf S, Levison SW, Barnum SR (2001) Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage. Brain Res 894(2):321–6
Spiegel K, Emmerling M, Barnum S (1998) Strategies for inhibition of complement activation in the treatment of neurodegenerative diseases. In: Wood PL (ed) Neuroinflammation: mechanisms and management. Humana, Totowa, NJ, p 375
Thomas A et al (2000) Expression of a complete and functional complement system by human neuronal cells in vitro. Int Immunol 12(7):1015–23
D’Ambrosio AL, Pinsky DJ, Connolly ES (2001) The role of the complement cascade in ischemia/reperfusion injury: implications for neuroprotection. Mol Med 7(6):367–82
Gasque P et al (1993) Expression of the complement classical pathway by human glioma in culture. A model for complement expression by nerve cells. J Biol Chem 268(33):25068–74
Gasque P et al (1992) Expression of complement components of the alternative pathway by glioma cell lines. J Immunol 149(4):1381–7
van Beek J, Elward K, Gasque P (2003) Activation of complement in the central nervous system: roles in neurodegeneration and neuroprotection. Ann N Y Acad Sci 992:56–71
Thrane AS, Skehan JD, Thrane PS (2007) A novel interpretation of immune redundancy and duality in reperfusion injury with important implications for intervention in ischaemic disease. Med Hypotheses 68(6):1363–70
Ducruet AF et al (2011) The neuroprotective effect of genetic mannose-binding lectin deficiency is not sustained in the sub-acute phase of stroke. Transl Stroke Res 2(4):588–99
Yano T et al (2003) Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia–reperfusion injury in rats. Anesthesiology 98(2):465–73
Shimakura A et al (2000) Neutrophil elastase inhibition reduces cerebral ischemic damage in the middle cerebral artery occlusion. Brain Res 858(1):55–60
Qureshi AI et al (2001) Spontaneous intracerebral hemorrhage. N Engl J Med 344(19):1450–60
Xi G et al (2001) Mechanisms of edema formation after intracerebral hemorrhage: effects of extravasated red blood cells on blood flow and blood–brain barrier integrity. Stroke 32(12):2932–8
Clark A et al (2008) Evidence for non-traditional activation of complement factor C3 during murine liver regeneration. Mol Immunol 45(11):3125–32
Gong Y et al (2005) Complement inhibition attenuates brain edema and neurological deficits induced by thrombin. Acta Neurochir Suppl 95:389–92
Kitaoka T et al (2002) Delayed argatroban treatment reduces edema in a rat model of intracerebral hemorrhage. Stroke 33(12):3012–8
Matsuoka H, Hamada R (2002) Role of thrombin in CNS damage associated with intracerebral haemorrhage: opportunity for pharmacological intervention? CNS Drugs 16(8):509–16
Hua Y et al (2007) Brain injury after intracerebral hemorrhage: the role of thrombin and iron. Stroke 38(2 Suppl):759–62
Rynkowski MA et al (2009) C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage. J Cereb Blood Flow Metab 29(1):98–107
Lucchesi BR (1993) Complement activation, neutrophils, and oxygen radicals in reperfusion injury. Stroke 24(12):I41–7
Xi G et al (2002) Brain edema after intracerebral hemorrhage: the effects of systemic complement depletion. Acta Neurochir Suppl 81:253–6
Aronowski J, Hall CE (2005) New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies. Neurol Res 27(3):268–79
Okusawa S et al (1988) C5a stimulates secretion of tumor necrosis factor from human mononuclear cells in vitro. Comparison with secretion of interleukin 1 beta and interleukin 1 alpha. J Exp Med 168(1):443–8
Lee KR et al (1997) Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood–brain barrier permeability, and cell survival in a rat model. J Neurosurg 86(2):272–8
Muller-Eberhard HJ (1986) The membrane attack complex of complement. Annu Rev Immunol 4:503–28
Wu J et al (2003) Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 34(12):2964–9
Xi G, Keep RF, Hoff JT (1998) Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 89(6):991–6
Wang X et al (2002) Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons: caspase activation and oxidative stress. Stroke 33(7):1882–8
Wagner KR et al (2003) Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 23(6):629–52
Gasque P et al (1998) The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis. J Immunol 160(7):3543–54
Head E et al (2001) Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down syndrome. Neurobiol Dis 8(2):252–65
Matsuoka Y et al (2001) Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer’s disease. Am J Pathol 158(4):1345–54
Eikelenboom P et al (1989) Complement activation in amyloid plaques in Alzheimer’s dementia. Virchows Arch B Cell Pathol Incl Mol Pathol 56(4):259–62
McGeer PL et al (1989) Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci Lett 107(1–3):341–6
Yasuhara O et al (1994) Expression of the complement membrane attack complex and its inhibitors in Pick disease brain. Brain Res 652(2):346–9
Singhrao SK et al (1996) Role of complement in the aetiology of Pick’s disease? J Neuropathol Exp Neurol 55(5):578–93
Kasuya H, Shimizu T (1989) Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage. J Neurosurg 71(5 Pt 1):741–6
Mack WJ et al (2007) Early plasma complement C3a levels correlate with functional outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 61(2):255–60, discussion 260-1
Yates JR et al (2007) Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med 357(6):553–61
Rancan M et al (2003) Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice. J Cereb Blood Flow Metab 23(9):1070–4
Bellander BM et al (2001) Complement activation in the human brain after traumatic head injury. J Neurotrauma 18(12):1295–311
Kaczorowski SL et al (1995) Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. J Cereb Blood Flow Metab 15(5):860–4
Keeling KL et al (2000) Local neutrophil influx following lateral fluid-percussion brain injury in rats is associated with accumulation of complement activation fragments of the third component (C3) of the complement system. J Neuroimmunol 105(1):20–30
Morganti-Kossmann M-C et al (2002) Inflammatory responses to traumatic brain injury: an overview for the new millennium. In: Rothwwell N, Lodick S (eds) Immune and inflammatory responses in the nervous system. Oxford University Press, Oxford, UK
Nataf S et al (1999) Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Trends Neurosci 22(9):397–402
Stahel PF, Morganti-Kossmann MC, Kossmann T (1998) The role of the complement system in traumatic brain injury. Brain Res Brain Res Rev 27(3):243–56
Stahel PF et al (2001) Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood–brain barrier dysfunction in patients with traumatic brain injury. J Neurotrauma 18(8):773–81
Gasque P et al (1996) Complement activation on human neuroblastoma cell lines in vitro: route of activation and expression of functional complement regulatory proteins. J Neuroimmunol 66(1–2):29–40
Singhrao SK et al (2000) Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. Am J Pathol 157(3):905–18
Figueroa E et al (2005) The administration of cobra venom factor reduces post-ischemic cerebral injury in adult and neonatal rats. Neurosci Lett 380(1–2):48–53
Vasthare US et al (1998) Complement depletion improves neurological function in cerebral ischemia. Brain Res Bull 45(4):413–9
Akita N et al (2001) The effect of C 1 esterase inhibitor on ischemia: reperfusion injury in the rat brain. No To Shinkei 53(7):641–4
De Simoni MG et al (2003) Neuroprotection by complement (C1) inhibitor in mouse transient brain ischemia. J Cereb Blood Flow Metab 23(2):232–9
De Simoni MG et al (2004) The powerful neuroprotective action of C1-inhibitor on brain ischemia-reperfusion injury does not require C1q. Am J Pathol 164(5):1857–63
Weisman HF et al (1990) Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 249(4965):146–51
Mocco J et al (2006) Preclinical evaluation of the neuroprotective effect of soluble complement receptor type 1 in a nonhuman primate model of reperfused stroke. J Neurosurg 105(4):595–601
Ducruet AF et al (2007) Pre-clinical evaluation of an sLe x-glycosylated complement inhibitory protein in a non-human primate model of reperfused stroke. J Med Primatol 36(6):375–80
Kilgore KS et al (1998) Attenuation of interleukin-8 expression in C6-deficient rabbits after myocardial ischemia/reperfusion. J Mol Cell Cardiol 30(1):75–85
Mack WJ et al (2006) Temporal pattern of C1q deposition after transient focal cerebral ischemia. J Neurosci Res 83(5):883–9
Mocco J et al (2006) Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res 99(2):209–17
Mocco J et al (2006) Alterations in plasma complement levels after human ischemic stroke. Neurosurgery 59(1):28–33, discussion 28–33
Furuya K et al (2001) Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke 32(11):2665–74
Vuorte J et al (1999) Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood. J Immunol 162(4):2353–7
Pedersen ED et al (2009) In situ deposition of complement in human acute brain ischaemia. Scand J Immunol 69(6):555–62
Xi G, Keep RF, Hoff JT (2002) Pathophysiology of brain edema formation. Neurosurg Clin N Am 13(3):371–83
Wu G, Huang FP (2005) Effects of venom defibrase on brain edema after intracerebral hemorrhage in rats. Acta Neurochir Suppl 95:381–7
Nakamura T et al (2004) Intracerebral hemorrhage in mice: model characterization and application for genetically modified mice. J Cereb Blood Flow Metab 24(5):487–94
Mukherjee P, Pasinetti GM (2000) The role of complement anaphylatoxin C5a in neurodegeneration: implications in Alzheimer’s disease. J Neuroimmunol 105(2):124–30
Ducruet AF et al (2008) C3a receptor modulation of granulocyte infiltration after murine focal cerebral ischemia is reperfusion dependent. J Cereb Blood Flow Metab 28(5):1048–58
Yang S et al (2006) The role of complement C3 in intracerebral hemorrhage-induced brain injury. J Cereb Blood Flow Metab 26(12):1490–5
Yang S et al (2006) Intracerebral hemorrhage in complement C3-deficient mice. Acta Neurochir Suppl 96:227–31
Rynkowski MA et al (2008) A mouse model of intracerebral hemorrhage using autologous blood infusion. Nat Protoc 3(1):122–8
Garrett MC et al (2009) Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage. Brain Res 1298:171–7
Mevorach D (1999) The immune response to apoptotic cells. Ann N Y Acad Sci 887:191–8
Mevorach D (2000) Opsonization of apoptotic cells. Implications for uptake and autoimmunity. Ann N Y Acad Sci 926:226–35
Mevorach D (2003) Systemic lupus erythematosus and apoptosis: a question of balance. Clin Rev Allergy Immunol 25(1):49–60
Mevorach D et al (1998) Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188(12):2313–20
Fishelson Z, Attali G, Mevorach D (2001) Complement and apoptosis. Mol Immunol 38(2–3):207–19
Wyss-Coray T et al (2002) Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice. Proc Natl Acad Sci USA 99(16):10837–42
Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407(6805):784–8
Fadok VA (1999) Clearance: the last and often forgotten stage of apoptosis. J Mammary Gland Biol Neoplasia 4(2):203–11
Fadok VA et al (1998) The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death Differ 5(7):551–62
Fadok VA, Henson PM (1998) Apoptosis: getting rid of the bodies. Curr Biol 8(19):R693–5
Fadok VA et al (1998) CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (alpha v beta 3). J Immunol 161(11):6250–7
Elward K, Gasque P (2003) “Eat me” and “don’t eat me” signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol Immunol 40(2–4):85–94
Savill J (2000) Apoptosis in resolution of inflammation. Kidney Blood Press Res 23(3–5):173–4
Fadok VA, Chimini G (2001) The phagocytosis of apoptotic cells. Semin Immunol 13(6):365–72
Savill J (1997) Apoptosis in resolution of inflammation. J Leukoc Biol 61(4):375–80
De Simone R et al (2003) Apoptotic PC12 cells exposing phosphatidylserine promote the production of anti-inflammatory and neuroprotective molecules by microglial cells. J Neuropathol Exp Neurol 62(2):208–16
Strey CW et al (2003) The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med 198(6):913–23
Markiewski MM et al (2004) C3a and C3b activation products of the third component of complement (C3) are critical for normal liver recovery after toxic injury. J Immunol 173(2):747–54
DeAngelis RA, Markiewski MM, Lambris JD (2006) Liver regeneration: a link to inflammation through complement. Adv Exp Med Biol 586:17–34
Shen J et al (2008) Neurogenesis after primary intracerebral hemorrhage in adult human brain. J Cereb Blood Flow Metab 28(8):1460–8
Yang S et al (2008) Effects of thrombin on neurogenesis after intracerebral hemorrhage. Stroke 39(7):2079–84
Bogestal YR et al (2007) Signaling through C5aR is not involved in basal neurogenesis. J Neurosci Res 85(13):2892–7
Moriyama M et al (2011) Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis. J Neurosci 31(11):3981–9
Ducruet AF et al (2012) Complement inhibition promotes endogenous neurogenesis and sustained anti-inflammatory neuroprotection following reperfused stroke. PLoS One 7(6):e38664
Arumugam TV et al (2009) Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience 158(3):1074–89
Hughes RA, Cornblath DR (2005) Guillain–Barre syndrome. Lancet 366(9497):1653–66
Archelos JJ, Fazekas F (2006) IVIG therapy in neurological disorders of childhood. J Neurol 253(Suppl 5):V80–6
Ringel I, Zettl UK (2006) Intravenous immunoglobulin therapy in neurological diseases during pregnancy. J Neurol 253(Suppl 5):V70–4
Stangel M, Pul R (2006) Basic principles of intravenous immunoglobulin (IVIg) treatment. J Neurol 253(Suppl 5):V18–24
Arumugam TV et al (2007) Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proc Natl Acad Sci USA 104(35):14104–9
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
McDowell, M., Shea, N., Gupta, G., Connolly, E.S. (2014). The Complement Cascade in Acute Brain Injury. In: Chen, J., Hu, X., Stenzel-Poore, M., Zhang, J. (eds) Immunological Mechanisms and Therapies in Brain Injuries and Stroke. Springer Series in Translational Stroke Research, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8915-3_5
Download citation
DOI: https://doi.org/10.1007/978-1-4614-8915-3_5
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-8914-6
Online ISBN: 978-1-4614-8915-3
eBook Packages: MedicineMedicine (R0)