Recovery from spinal cord injury using naturally occurring antiinflammatory compound curcumin

Laboratory investigation

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Object

Spinal cord injury (SCI) is a debilitating disease. Primary SCI results from direct injury to the spinal cord, whereas secondary injury is a side effect from subsequent edema and ischemia followed by activation of proinflammatory cytokines. These cytokines activate the prosurvival molecule nuclear factor–κB and generate obstacles in spinal cord reinnervation due to gliosis. Curcumin longa is an active compound found in turmeric, which acts as an antiinflammatory agent primarily by inhibiting nuclear factor–κB. Here, the authors study the effect of curcumin on SCI recovery.

Methods

Fourteen female Sprague-Dawley rats underwent T9–10 laminectomy and spinal cord contusion using a weight-drop apparatus. Within 30 minutes after contusion and weekly thereafter, curcumin (60 mg/kg/ml body weight in dimethyl sulfoxide) or dimethyl sulfoxide (1 ml/kg body weight) was administered via percutaneous epidural injection at the injury site. Spinal cord injury recovery was assessed weekly by scoring hindlimb motor function. Animals were killed 6 weeks postcontusion for histopathological analysis of spinal cords and soleus muscle weight evaluation.

Results

Curcumin-treated rats had improved motor function compared with controls starting from Week 1. Body weight gain significantly improved, correlating with improved Basso-Beattie-Bresnahan scores. Soleus muscle weight was greater in curcumin-treated rats than controls. Histopathological analysis validated these results with increased neural element mass with less gliosis at the contusion site in curcumin-treated rats than controls.

Conclusions

Epidural administration of curcumin resulted in improved recovery from SCI. This occurred with no adverse effects noted in experimental animals. Therefore, curcumin treatment may translate into a novel therapy for humans with SCI.

Abbreviations used in this paper:BBB = Basso-Beattie-Bresnahan; DMSO = dimethyl sulfoxide; MDA = 3,4-methylenedioxyamphetamine; NF-κB = nuclear factor–κB; SCI = spinal cord injury; SOD = superoxide dismutase.

Article Information

Address correspondence to: Meena Jhanwar-Uniyal, Ph.D., Departments of Neurosurgery and Pathology, New York Medical College, Valhalla, New York 10595. email: meena_jhanwar@nymc.edu.

Please include this information when citing this paper: published online February 10, 2012; DOI: 10.3171/2012.1.SPINE11769.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Functional analysis after curcumin treatment after SCI. A: Basso-Beattie-Bresnahan scores. Curcumin-treated animals (solid line) recovered more rapidly and better than DMSO-treated animals (dashed line). B: Body weight over time. Curcumin-treated rats (solid line) showed improved body weight gain over vehicle (DMSO)-treated rats (dashed line). C: Soleus muscle weight. Rats with greater recovery of hindlimb motor function have better soleus muscle weight at necropsy. Curcumin-treated animals (shaded bar) had a heavier soleus muscle weight than DMSO controls (open bar). Values presented are mean ± SEM. *p < 0.05.

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    Histopathological analysis. A: Curcumin-treated animals (solid line) showed greater sparing of neurological tissue than DMSO controls (dashed line). A value of 0 represents the area of peak contusion/spinal cord atrophy. B and C: Curcumintreated animals (shaded bar) have more spared spinal cord tissue than control animals (open bar). This includes total area (B) as well as gray and white matter (C). D and E: Photomicrographs showing an increased sparing of tissue and decreased gliosis after curcumin treatment (E) versus DMSO treatment (D). Values are mean ± SEM, where control = 100. *p < 0.05; $p < 0.1 (trend toward significance). H & E, original magnification × 10.

References

1

Aebi MMohler JZäch GAMorscher E: Indication, surgical technique, and results of 100 surgically-treated fractures and fracture-dislocations of the cervical spine. Clin Orthop Relat Res 203:2442571986

2

Aggarwal BBHarikumar KB: Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40592009

3

Aggarwal BBSung B: Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci 30:85942009

4

Albert TJKim DH: Timing of surgical stabilization after cervical and thoracic trauma. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004. J Neurosurg Spine 3:1821902005

5

Ammon HPWahl MA: Pharmacology of Curcuma longa. Planta Med 57:171991

6

Anand PKunnumakkara ABNewman RAAggarwal BB: Bioavailability of curcumin: problems and promises. Mol Pharm 4:8078182007

7

Basso DMBeattie MSBresnahan JC: Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:2442561996

8

Begum ANJones MRLim GPMorihara TKim PHeath DD: Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther 326:196208

9

Brambilla RHurtado APersaud TEsham KPearse DDOudega M: Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury. J Neurochem 110:7657782009

10

Cemil BTopuz KDemircan MNKurt GTun KKutlay M: Curcumin improves early functional results after experimental spinal cord injury. Acta Neurochir (Wien) 152:158315902010

11

Chainani-Wu N: Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med 9:1611682003

12

Christopher & Dana Reeve Foundation: One Degree of Separation: Paralysis and Spinal Cord Injury in the United States 2009. (http://www.christopherreeve.org/site/c.ddJFKRNoFiG/b.5091685/k.58BD/One_Degree_of_Separation.htm) [Accessed January 7 2012]

13

Eriksson CTehranian RIverfeldt KWinblad BSchultzberg M: Increased expression of mRNA encoding interleukin-1beta and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration. J Neurosci Res 60:2662792000

14

Fleming JCNorenberg MDRamsay DADekaban GAMarcillo AESaenz AD: The cellular inflammatory response in human spinal cords after injury. Brain 129:324932692006

15

Friese MAFugger L: Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?. Brain 128:174717632005

16

Gris DMarsh DROatway MAChen YHamilton EFDekaban GA: Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci 24:404340512004

17

Gruner JA: A monitored contusion model of spinal cord injury in the rat. J Neurotrauma 9:1231281992

18

Hauben ESchwartz M: Therapeutic vaccination for spinal cord injury: helping the body to cure itself. Trends Pharmacol Sci 24:7122003

19

Kerwin AJGriffen MMTepas JJ IIISchinco MADevin TFrykberg ER: Best practice determination of timing of spinal fracture fixation as defined by analysis of the National Trauma Data Bank. J Trauma 65:8248312008

20

Kim SJSon TGPark HRPark MKim MSKim HS: Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 283:14497145052008

21

Lin MSLee YHChiu WTHung KS: Curcumin provides neuroprotection after spinal cord injury. J Surg Res 166:2802892011

22

Lin MSSun YYChiu WTHung CCChang CYShie FS: Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide-induced astrocyte reactivation in vitro. J Neurotrauma 28:125912692011

23

Marshall LFKnowlton SGarfin SRKlauber MREisenberg HMKopaniky D: Deterioration following spinal cord injury. A multicenter study. J Neurosurg 66:4004041987

24

Noble LJDonovan FIgarashi TGoussev SWerb Z: Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J Neurosci 22:752675352002

25

Popovich PGGuan ZMcGaughy VFisher LHickey WFBasso DM: The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. J Neuropathol Exp Neurol 61:6236332002

26

Rabchevsky AGStreit WJ: Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res 47:34481997

27

Rafati DSGeissler KJohnson KUnabia GHulsebosch CNesic-Taylor O: Nuclear factor-kappaB decoy amelioration of spinal cord injury-induced inflammation and behavior outcomes. J Neurosci Res 86:5665802008

28

Renault-Mihara FOkada SShibata SNakamura MToyama YOkano H: Spinal cord injury: emerging beneficial role of reactive astrocytes' migration. Int J Biochem Cell Biol 40:164916532008

29

Rice TLarsen JRivest SYong VW: Characterization of the early neuroinflammation after spinal cord injury in mice. J Neuropathol Exp Neurol 66:1841952007

30

Sahin Kavaklı HKoca CAlıcı O: Antioxidant effects of curcumin in spinal cord injury in rats. Ulus Travma Acil Cerrahi Derg 17:14182011

31

Satoskar RRShah SJShenoy SG: Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol 24:6516541986

32

Schwartz M: Macrophages and microglia in central nervous system injury: are they helpful or harmful?. J Cereb Blood Flow Metab 23:3853942003

33

Sekhon LHFehlings MG: Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine (Phila Pa 1976) 26:24 SupplS2S122001

34

Shankar TNShantha NVRamesh HPMurthy IAMurthy VS: Toxicity studies on turmeric (Curcuma longa): acute toxicity studies in rats, guineapigs & monkeys. Indian J Exp Biol 18:73751980

35

Sharma RAEuden SAPlatton SLCooke DNShafayat AHewitt HR: Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10:684768542004

36

Taoka YOkajima KUchiba MMurakami KKushimoto SJohno M: Role of neutrophils in spinal cord injury in the rat. Neuroscience 79:117711821997

37

Vaccaro ARDaugherty RJSheehan TPDante SJCotler JMBalderston RA: Neurologic outcome of early versus late surgery for cervical spinal cord injury. Spine (Phila Pa 1976) 22:260926131997

38

Wang TDWang YHHuang TSSu TCPan SLChen SY: Circulating levels of markers of inflammation and endothelial activation are increased in men with chronic spinal cord injury. J Formos Med Assoc 106:9199282007

39

Zeman RJFeng YPeng HEtlinger JD: Clenbuterol, a beta(2)-adrenoceptor agonist, improves locomotor and histological outcomes after spinal cord contusion in rats. Exp Neurol 159:2672731999

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