Effect of rosuvastatin on cytokines after traumatic head injury

Clinical article

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  • 1 Departments of Clinical Epidemiology and
  • 5 Nuclear Medicine Laboratory, Universidad Autónoma de San Luis Potosí
  • 3 Departments of Neurosurgery and
  • 4 Neuropsychology and Rehabilitation, Hospital Central “Dr. Ignacio Morones Prieto,” San Luis Potosí, México; and
  • 2 Klinik für Neurochirurgie, Otto-von-Guericke Universität, Magdeburg, Germany
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Object

The favorable effect of statin treatment after traumatic brain injury (TBI) has been shown in animal studies and is probably true in humans as well. The objective of this study was to determine whether acute statin treatment following TBI could reduce inflammatory cytokines and improve functional outcomes in humans.

Methods

The authors performed a double-blind randomized clinical trial in patients with moderate to severe TBI. Exclusion criteria were as follows: prior severe disability; use of modifiers of statin metabolism; multisystem trauma; prior use of mannitol, barbiturates, corticosteroids, or calcium channel blockers; isolated brainstem lesions; allergy to statins; previous hepatopathy or myopathy; previous treatment at another clinic; and pregnancy. Patients were randomly selected to receive 20 mg of rosuvastatin or placebo for 10 days. The main goal was to determine the effect of rosuvastatin on plasma levels of tumor necrosis factor–α, interleukin (IL)–1β, IL-6, and IL-10 after 72 hours of TBI. Amnesia, disorientation, and disability were assessed 3 and 6 months after TBI.

Results

Thirty-six patients were analyzed according to intention-to-treat analysis; 19 patients received rosuvastatin and 17 received placebo. The best-fit mixed model showed a significant effect of rosuvastatin on the reduction of tumor necrosis factor–α levels (p = 0.004). Rosuvastatin treatment did not appear to affect the levels of IL-1β, IL-6, and IL-10. The treatment was associated with a reduction in disability scores (p = 0.03), indicating a favorable functional outcome. Life-threatening adverse effects were not observed.

Conclusions

The authors' data suggest that statins may induce an antiinflammatory effect and may promote recovery after TBI. The role of statins in TBI therapy should be confirmed in larger clinical trials. Clinical trial registration no.: NCT00990028.

Abbreviations used in this paper:ALT = alanine transaminase; AST = aspartate transaminase; CK = creatine kinase; DRS = Disability Rating Scale; GCS = Glasgow Coma Scale; GOAT = Galveston Orientation Amnesia Test; IL = interleukin; TBI = traumatic brain injury; TCDB = Traumatic Coma Data Bank; TNFα = tumor necrosis factor–α.

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Contributor Notes

* Drs. Sánchez-Aguilar and Tapia-Pérez contributed equally to this work.

Address correspondence to: Martin Sánchez-Aguilar, M.Sc., Department of Clinical Epidemiology, Universidad Autónoma de San Luis Potosí, Av. Venustiano Carranza 2405, San Luis Potosí 78210, México. email: jemarsan7@hotmail.com.

Please include this information when citing this paper: published online January 4, 2013; DOI: 10.3171/2012.12.JNS121084.

  • 1

    Berger RP, , Ta'asan S, , Rand A, , Lokshin A, & Kochanek P: Multiplex assessment of serum biomarker concentrations in well-appearing children with inflicted traumatic brain injury. Pediatr Res 65:97102, 2009

    • Search Google Scholar
    • Export Citation
  • 2

    Chauhan NB, & Gatto R: Restoration of cognitive deficits after statin feeding in TBI. Restor Neurol Neurosci 29:2334, 2011

  • 3

    Chen G, , Zhang S, , Shi J, , Ai J, , Qi M, & Hang C: Simvastatin reduces secondary brain injury caused by cortical contusion in rats: possible involvement of TLR4/NF-kappaB pathway. Exp Neurol 216:398406, 2009

    • Search Google Scholar
    • Export Citation
  • 4

    Crespo AR, , Da Rocha AB, , Jotz GP, , Schneider RF, , Grivicich I, & Pinheiro K, : Increased serum sFas and TNFalpha following isolated severe head injury in males. Brain Inj 21:441447, 2007

    • Search Google Scholar
    • Export Citation
  • 5

    Floyd JS, , Heckbert SR, , Weiss NS, , Carrell DS, & Psaty BM: Use of administrative data to estimate the incidence of statin-related rhabdomyolysis. JAMA 307:15801582, 2012

    • Search Google Scholar
    • Export Citation
  • 6

    Greenwood J, , Steinman L, & Zamvil SS: Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol 6:358370, 2006

    • Search Google Scholar
    • Export Citation
  • 7

    Heegaard W, & Biros M: Traumatic brain injury. Emerg Med Clin North Am 25:655678, viii, 2007

  • 8

    Helmy A, , Carpenter KL, , Menon DK, , Pickard JD, & Hutchinson PJ: The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production. J Cereb Blood Flow Metab 31:658670, 2011

    • Search Google Scholar
    • Export Citation
  • 9

    Helmy A, , Timofeev I, , Palmer CR, , Gore A, , Menon DK, & Hutchinson PJ: Hierarchical log linear analysis of admission blood parameters and clinical outcome following traumatic brain injury. Acta Neurochir (Wien) 152:953957, 2010

    • Search Google Scholar
    • Export Citation
  • 10

    Hensler T, , Sauerland S, , Riess P, , Hess S, , Helling HJ, & Andermahr J, : The effect of additional brain injury on systemic interleukin (IL)-10 and IL-13 levels in trauma patients. Inflamm Res 49:524528, 2000

    • Search Google Scholar
    • Export Citation
  • 11

    Levin HS, , O'Donnell VM, & Grossman RG: The Galveston Orientation and Amnesia Test. A practical scale to assess cognition after head injury. J Nerv Ment Dis 167:675684, 1979

    • Search Google Scholar
    • Export Citation
  • 12

    Li B, , Mahmood A, , Lu D, , Wu H, , Xiong Y, & Qu C, : Simvastatin attenuates microglial cells and astrocyte activation and decreases interleukin-1beta level after traumatic brain injury. Neurosurgery 65:179186, 2009

    • Search Google Scholar
    • Export Citation
  • 13

    Lu D, , Qu C, , Goussev A, , Jiang H, , Lu C, & Schallert T, : Statins increase neurogenesis in the dentate gyrus, reduce delayed neuronal death in the hippocampal CA3 region, and improve spatial learning in rat after traumatic brain injury. J Neurotrauma 24:11321146, 2007

    • Search Google Scholar
    • Export Citation
  • 14

    Lucas SM, , Rothwell NJ, & Gibson RM: The role of inflammation in CNS injury and disease. Br J Pharmacol 147:1 Suppl 1 S232S240, 2006

  • 15

    Mahmood A, , Goussev A, , Kazmi H, , Qu C, , Lu D, & Chopp M: Long-term benefits after treatment of traumatic brain injury with simvastatin in rats. Neurosurgery 65:187192, 2009

    • Search Google Scholar
    • Export Citation
  • 16

    Maier B, , Schwerdtfeger K, , Mautes A, , Holanda M, , Müller M, & Steudel WI, : Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury. Shock 15:421426, 2001

    • Search Google Scholar
    • Export Citation
  • 17

    Marshall LF, , Marshall SB, , Klauber MR, , van Berkum Clark M, , Eisenberg HM, & Jane JA, : A new classification of head injury based on computerized tomography. J Neurosurg 75:S14S20, 1991

    • Search Google Scholar
    • Export Citation
  • 18

    Rappaport M, , Hall KM, , Hopkins K, , Belleza T, & Cope DN: Disability rating scale for severe head trauma: coma to community. Arch Phys Med Rehabil 63:118123, 1982

    • Search Google Scholar
    • Export Citation
  • 19

    Schmidt OI, , Leinhase I, , Hasenboehler E, , Morgan SJ, & Stahel PF: [The relevance of the inflammatory response to the injured brain.]. Orthopade 36:248258, 2007. (Ger)

    • Search Google Scholar
    • Export Citation
  • 20

    Schneider EB, , Efron DT, , MacKenzie EJ, , Rivara FP, , Nathens AB, & Jurkovich GJ: Premorbid statin use is associated with improved survival and functional outcomes in older head-injured individuals. J Trauma 71:815819, 2011

    • Search Google Scholar
    • Export Citation
  • 21

    Tapia-Pérez JH, , Sanchez-Aguilar M, & Schneider T: The role of statins in neurosurgery. Neurosurg Rev 33:259270, 2010

  • 22

    Tapia-Perez JH, , Sanchez-Aguilar M, , Torres-Corzo JG, , Gordillo-Moscoso A, , Martinez-Perez P, & Madeville P, : Effect of rosuvastatin on amnesia and disorientation after traumatic brain injury (NCT003229758). J Neurotrauma 25:10111017, 2008

    • Search Google Scholar
    • Export Citation
  • 23

    Turkoglu OF, , Eroglu H, , Okutan O, , Gurcan O, , Bodur E, & Sargon MF, : Atorvastatin efficiency after traumatic brain injury in rats. Surg Neurol 72:146152, 2009

    • Search Google Scholar
    • Export Citation
  • 24

    Wible EF, & Laskowitz DT: Statins in traumatic brain injury. Neurotherapeutics 7:6273, 2010

  • 25

    Wood WG, , Eckert GP, , Igbavboa U, & Müller WE: Statins and neuroprotection: a prescription to move the field forward. Ann N Y Acad Sci 1199:6976, 2010

    • Search Google Scholar
    • Export Citation

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