Cerebral Palsy: Treatments and Therapeutics


Cerebral palsy (CP) is a non‐progressive motor disorder affecting approximately 3 out of every 1000 infants in the United States. Although it is classified as a motor disorder, the deficits are caused by pre‐ or neonatal brain injury. Unfortunately, there is no cure for CP and currently, symptom management is the only treatment option available. As research begins to unravel the underlying causes and cellular changes leading to CP, potential treatments and therapeutics can be investigated to prevent brain damage following insults. Today, only two therapies are approved for use in the hospital setting: hypothermia and magnesium sulphate. Both of these therapies attempt to lessen the brain damage by slowing processes of inflammation and cell death. Other potential therapies are in clinical trials to test safety and efficacy for use in humans. Some drugs have shown promise in animal models; however, they have not yet been tested in humans. Researchers are searching for a cure.

Key Concepts

  • There is no cure for cerebral palsy and currently approved treatments target the symptoms of cerebral palsy, not the underlying causes.
  • Hypothermia and magnesium sulphate are the only two therapeutics used in the hospital setting to slow or lessen brain damage following labour and delivery complications.
  • Therapeutics targeting the excitatory amino acid neurotransmitter glutamate, along with glutamate receptor and transporter expression and function, appear to be promising.
  • Drug treatments targeting growth factors and endogenous proteins may be beneficial to reduce cell death leading to cerebral palsy.
  • Because inflammation plays a role in cerebral palsy, drug treatment that reduces the inflammatory response may also reduce brain damage following insults.

Keywords: cerebral palsy; drug therapy; growth factors; glutamate; glutamate receptors; glutamate transporters; inflammation

Figure 1. Treatments and therapeutics for acquired cerebral palsy. There are many different causes of acquired cerebral palsy and many potential treatments. Blue squares with black arrows represent potential causes leading to cerebral palsy (red box). The green boxes with red arrows indicate potential therapeutic interventions at each stage.
Figure 2. Treatments and therapeutics for congenital cerebral palsy. The underlying causes of congenital cerebral palsy are not known, but based upon the type of injury seen in cerebral palsy patients, infections and hypoxia‐ischemia are thought to account for the majority of congenital CP cases. Blue squares with black arrows represent potential causes leading to cerebral palsy (red box). The green boxes with red arrows indicate potential therapeutic interventions at each stage.


Ahn SY, Chang YS, Sung DK, et al. (2013) Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage. Stroke 44: 497–504.

Alonso‐Alconada D, Alvarez FJ, Alvarez A, et al. (2010) The cannabinoid receptor agonist WIN 55,212‐2 reduces the initial cerebral damage after hypoxic‐ischemic injury in fetal lambs. Brain Research 1362: 150–159.

Alvarez FJ, Lafuente H, Rey‐Santano MC, et al. (2008) Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic‐ischemic newborn piglets. Pediatric Research 64: 653–658.

Atici A, Bozlu G, Turhan AH, et al. (2008) The role of trapidil on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury. Early Human Development 84: 243–247.

Awad N, Khatib N, Ginsberg Y, et al. (2011) N‐acetyl‐cysteine (NAC) attenuates LPS‐induced maternal and amniotic fluid oxidative stress and inflammatory responses in the preterm gestation. American Journal of Obstetrics & Gynecology 204: 450.e15–e20.

Azbill RD, Mu X and Springer JE (2000) Riluzole increases high‐affinity glutamate uptake in rat spinal cord synaptosomes. Brain Research 871: 175–180.

Beloosesky R (2011) Magnesium sulfate may offer protection from cerebral palsy. Neurology Reviews 19: 13.

Beloosesky R, Gayle DA, Amidi F, et al. (2006) N‐acetyl‐cysteine suppresses amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats. American Journal of Obstetrics and Gynecology 194: 268–273.

Beloosesky R, Weiner Z, Khativ N, et al. (2009) Prophylactic maternal n‐acetylcysteine before lipopolysaccharide suppresses fetal inflammatory cytokine responses. American Journal of Obstetrics & Gynecology 200: 665.e1–e5.

Bozlu G, Atici A, Turhan AH, et al. (2007) Platelet‐activating factor antagonist (ABT‐491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury. Brain Research 1143: 193–198.

Cai Z, Lin S, Fan LW, Pang Y and Rhodes PG (2006) Minocycline alleviates hypoxic–ischemic injury to developing oligodendrocytes in the neonatal rat brain. Neuroscience 137: 425–435.

Conde‐Agudelo A and Romero R (2009) Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. American Journal of Obstetrics and Gynecology 200: 595–609.

Doyle LW, Crowther CA, Middleton P and MARRET S (2009) Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstetrics & Gynecology 113: 1327–1333.

Fernández‐López D, Faustino J, Derugin N, et al. (2012) Reduced infarct size and accumulation of microglia in rats treated with WIN 55,212‐2 after neonatal stroke. Neuroscience 207: 307–315.

Fernández‐López D, Pradillo JM, García‐Yébenes I, et al. (2010) The cannabinoid WIN55212‐2 promotes neural repair after neonatal hypoxia‐ischemia. Stroke 41: 2956–2964.

Follett PL (2004) Glutamate receptor‐mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. Journal of Neuroscience 24: 4412–4420.

Follett PL, Rosenberg PA, Volpe JJ and Jensen FE (2000) NBQX attenuates excitotoxic injury in developing white matter. Journal of Neuroscience 20: 9235–9241.

Fulmer CG, VonDran MW, Stillman AA, et al. (2014) Astrocyte‐derived BDNF supports myelin protein synthesis after cuprizone‐induced demyelination. Journal of Neuroscience 34: 8186–8196.

Ganel R, Ho T, Maragakis NJ, et al. (2006) Selective up‐regulation of the glial Na+ − dependent glutamate transporter GLT1 by a neuroimmunophilin ligand results in neuroprotection. Neurobiology of Disease 21: 556–567.

Girard S, Kadhim H, Larouche A, et al. (2008) Pro‐inflammatory disequilibrium of the IL‐1 beta/IL‐1ra ratio in an experimental model of perinatal brain damages induced by lipopolysaccharide and hypoxia‐ischemia. Cytokine 43: 54–62.

Girard S, Tremblay L, Lepage M and Sébire G (2010) IL‐1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. Journal of Immunology 184: 3997–4005.

Gluckman PD, Wyatt JS, Azzopardi D, et al. (2005a) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365: 663–670.

Grimston SK, Silva MJ and Civitelli R (2007) Bone loss after temporarily induced muscle paralysis by Botox is not fully recovered after 12 weeks. Annals of the New York Academy of Sciences 1116: 444–460.

Hagberg H, Gilland E, Diemer NH and Andine P (1994) Hypoxia-ischemia in the neonatal rat brain: histopathology after post-treatment with NMDA and non-NMDA receptor antagonists. Biology of the Neonate 66: 205–213.

Huh Y, Ju MS, Park H, et al. (2010) Clavulanic acid protects neurons in pharmacological models of neurodegenerative diseases. Drug Development Research 71: 351–357.

Hung PL, Huang CC, Huang HM, Tu DG and Chang YC (2013) Thyroxin treatment protects against white matter injury in the immature brain via brain‐derived neurotrophic factor. Stroke 44: 2275–2283.

Im SH, Yu JH, Park ES, et al. (2010) Induction of striatal neurogenesis enhances functional recovery in an adult animal model of neonatal hypoxic‐ischemic brain injury. Neuroscience 169: 259–268.

Kalay S, Oztekin O, Tezel G, et al. (2013) The effects of intraperitoneal pentoxifylline treatment in rat pups with hypoxic‐ischemic encephalopathy. Pediatric Neurology 49: 319–323.

Kannan S, Dai H, Navath RS, et al. (2012) Dendrimer‐based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Science Translational Medicine 4: 130ra46.

Lai PC, Huang YT, Wu CC, et al. (2011) Ceftriaxone attenuates hypoxic‐ischemic brain injury in neonatal rats. Journal of Biomedical Science 18: 69.

Lee S‐G, Su Z‐Z, Emdad L, et al. (2008) Mechanism of ceftriaxone induction of excitatory amino acid transporter‐2 expression and glutamate uptake in primary human astrocytes. Journal of Biological Chemistry 283: 13116–13123.

Li H and Buchan AM (1993) Treatment with an AMPA antagonist 12 hours following severe normothermic forebrain ischemia prevents CA1 neuronal injury. Journal of Cerebral Blood Flow & Metabolism 13: 933–939.

Li M, Yu A, Zhang F, et al. (2012) Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells. Journal of Translational Medicine 10: 100.

Liu X‐H, Eun B‐L, Silverstein FS and Barks JDE (1996) The platelet‐activating factor antagonist BN 52021 attenuates hypoxic‐ischemic brain injury in the immature rat. Pediatric Research 40: 797–803.

Liu XH, Eun BL and Barks JD (2001) Platelet‐activating factor antagonist BN 50730 attenuates hypoxic‐ischemic brain injury in neonatal rats. Pediatric Research 49: 804–811.

Manning SM, Talos DM, Zhou C, et al. (2008) NMDA receptor blockade with memantine attenuates white matter injury in a rat model of periventricular leukomalacia. Journal of Neuroscience 28: 6670–6678.

Mao M, Hua Y, Jiang X, et al. (2006) Expression of tumor necrosis factor α and neuronal apoptosis in the developing rat brain after neonatal stroke. Neuroscience Letters 403: 227–232.

Mimura K, Tomimatsu T, Minato K, et al. (2011) Ceftriaxone preconditioning confers neuroprotection in neonatal rats through glutamate transporter 1 upregulation. Reproductive Sciences 18: 1193–1201.

Nelson KB and Grether JK (1995) Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics 95: 263–269.

Noh M‐R, Kim SK, Sun W, et al. (2006) Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats. Experimental Neurology 201: 470–478.

Okazaki K, Nishida A, Kato M, et al. (2006) Elevation of cytokine concentrations in asphyxiated neonates. Biology of the Neonate 89: 183–189.

Omouendze PL, Henry VJ, Porte B, et al. (2013) Hypoxia‐ischemia or excitotoxin‐induced tissue plasminogen activator‐ dependent gelatinase activation in mice neonate brain microvessels. PLoS One 8: e71263.

Pazos MR, Cinquina V, Gómez A, et al. (2012) Cannabidiol administration after hypoxia‐ischemia to newborn rats reduces long‐term brain injury and restores neurobehavioral function. Neuropharmacology 63: 776–783.

Purandare C, Shitole DG, Belle V, et al. (2012) Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Case Reports in Transplantation 2012: 825289.

Schäbitz W‐R, Berger C, Kollmar R, et al. (2004) Effect of brain‐derived neurotrophic factor treatment and forced arm use on functional motor recovery after small cortical ischemia. Stroke 35: 992–997.

Schubert S, Brandl U, Brodhun M, et al. (2005) Neuroprotective effects of topiramate after hypoxia‐ischemia in newborn piglets. Brain Research 1058: 129–136.

Seo MA, Lee HJ, Choi EJ, et al. (2010) Neuroprotective effect of dizocilpine (MK‐801) via anti‐apoptosis on hypoxic‐ischemic brain injury in neonatal rats. Journal of the Korean Society of Neonatology 17: 181–192.

Sfaello I, Baud O, Arzimanoglou A and Gressens P (2005) Topiramate prevents excitotoxic damage in the newborn rodent brain. Neurobiology of Disease 20: 837–848.

Shimada F, Shiga Y, Morikawa M, et al. (1999) The neuroprotective agent MS‐153 stimulates glutamate uptake. European Journal of Pharmacology 386: 263–270.

Thoresen M and Whitelaw A (2005) Therapeutic hypothermia for hypoxic‐ischaemic encephalopathy in the newborn infant. Current Opinion in Neurology 18: 111–116.

Thöne‐Reineke C, Neumann C, Namsolleck P, et al. (2008) The beta‐lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke. Journal of Hypertension 26: 2426–2435.

Tsuji M, Wilson MA, Lange MS and Johnston MV (2004) Minocycline worsens hypoxic‐ischemic brain injury in a neonatal mouse model. Experimental Neurology 189: 58–65.

van Velthoven CTJ, Kavelaars A, van Bel F and Heijnen CJ (2010) Mesenchymal stem cell treatment after neonatal hypoxic‐ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain, Behavior, and Immunity 24: 387–393.

Verma R, Mishra V, Sasmal D and Raghubir R (2010) European Journal of Pharmacology. European Journal of Pharmacology 638: 65–71.

Viswanath M, Palmer C and Roberts RL (2000) Reduction of hypoxic‐ischemic brain swelling in the neonatal rat with PAF antagonist WEB 2170: lack of long‐term protection. Pediatric Research 48: 109–113.

Wang S‐J, Wang K‐Y and Wang W‐C (2004) Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Neuroscience 125: 191–201.

Further Reading

Beloosesky R (2011) Magnesium sulfate may offer protection from cerebral palsy. Neurology Reviews 19: 13.

Borghesi A, Cova C, Gazzolo D and Stronati M (2013) Stem cell therapy for neonatal diseases associated with preterm birth. Journal of Clinical Neonatology 2: 1–7.

Gluckman PD, Wyatt JS, Azzopardi D, et al. (2005b) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365: 663–670.

Gunn AJ, Williams CE, Bennet L, Cook CJ and Gluckman PD (1988) Perinatal cerebral asphyxia: pharmacological intervention. Fetal Therapy 3: 98–107.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Feather‐Schussler, Danielle N, and Ferguson, Tanya S(Feb 2015) Cerebral Palsy: Treatments and Therapeutics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026121]