Review

. 2015 Apr 21;19(1):186.

doi: 10.1186/s13054-015-0887-8.

Neuroprotection in acute brain injury: an up-to-date review

Nino Stocchetti^{1

2}, Fabio S Taccone³, Giuseppe Citerio^{4

5}, Paul E Pepe⁶, Peter D Le Roux⁷, Mauro Oddo⁸, Kees H Polderman⁹, Robert D Stevens¹⁰, William Barsan¹¹, Andrew I R Maas¹², Geert Meyfroidt¹³, Michael J Bell¹⁴, Robert Silbergleit¹⁵, Paul M Vespa¹⁶, Alan I Faden¹⁷, Raimund Helbok¹⁸, Samuel Tisherman¹⁹, Elisa R Zanier²⁰, Terence Valenzuela²¹, Julia Wendon²², David K Menon²³, Jean-Louis Vincent²⁴

Affiliations

¹ Department of Physiopathology and Transplant, Milan University, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via F Sforza 35, 20122, Milan, Italy. stocchet@policlinico.mi.it.
² Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via F Sforza 35, 20122, Milan, Italy. stocchet@policlinico.mi.it.
³ Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070, Brussels, Belgium. ftaccone@ulb.ac.be.
⁴ Department of Health Science, University of Milan-Bicocca, Ospedale San Gerardo, Via Pergolesi 33, 20900, Monza, MB, Italy. g.citerio@hsgerardo.org.
⁵ NeuroIntensive Care, Department of Emergency and Intensive Care, Ospedale San Gerardo, Via Pergolesi 33, 20900, Monza, MB, Italy. g.citerio@hsgerardo.org.
⁶ Department of Emergency Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-8579, USA. Paul.Pepe@UTSouthwestern.edu.
⁷ Department of Neurosurgery, Lankenau Medical Center, Wynnewood, PA, 19096, USA. LeRouxP@MLHS.ORG.
⁸ Department of Intensive Care Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) University Hospital, Faculty of Biology and Medicine, University of Lausanne, 1011, Lausanne, Switzerland. Mauro.Oddo@chuv.ch.
⁹ Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA. poldermankh@upmc.edu.
¹⁰ Division of Neuroscience Critical Care, Division of Adult Critical Care, Johns Hopkins Medicine, Baltimore, MD, 21287, USA. rstevens@jhmi.edu.
¹¹ NETT Clinical Coordinating Center, University of Michigan, Ann Arbor, MI, 48106-0381, USA. wbarsan@med.umich.edu.
¹² Department of Neurosurgery, University Hospital Antwerp and University of Antwerp, 2650, Edegem, Belgium. andrew.maas@uza.be.
¹³ Department of Intensive Care, UZ Leuven, Campus Gasthuisberg, 3000, Leuven, Belgium. geert.meyfroidt@uzleuven.be.
¹⁴ Department of Critical Care Medicine and the Safar Center for Resuscitation Research, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA. bellmj4@upmc.edu.
¹⁵ NETT Clinical Coordinating Center, University of Michigan, Ann Arbor, MI, 48106-0381, USA. robie@med.umich.edu.
¹⁶ Department of Neurocritical Care, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. PVespa@mednet.ucla.edu.
¹⁷ Center for Shock, Trauma & Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD, 21201, USA. afaden@anes.umm.edu.
¹⁸ Department of Neurology, Neurocritical Care Unit, Innsbruck Medical University, 6020, Innsbruck, Austria. raimund.helbok@uki.at.
¹⁹ Department of Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. tishermansa@ccm.upmc.edu.
²⁰ IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, 20156, Milan, Italy. elisa.zanier@marionegri.it.
²¹ Department of Emergency Medicine, University of Arizona, Tucson, AZ, 85724-5057, USA. hermanos.valenzuela@gmail.com.
²² Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. julia.wendon@kcl.ac.uk.
²³ Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. dkm13@wbic.cam.ac.uk.
²⁴ Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070, Brussels, Belgium. jlvincen@ulb.ac.be.

PMID: 25896893
PMCID: PMC4404577
DOI: 10.1186/s13054-015-0887-8

Review

Neuroprotection in acute brain injury: an up-to-date review

Nino Stocchetti et al. Crit Care. 2015.

. 2015 Apr 21;19(1):186.

doi: 10.1186/s13054-015-0887-8.

Authors

Affiliations

¹ Department of Physiopathology and Transplant, Milan University, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via F Sforza 35, 20122, Milan, Italy. stocchet@policlinico.mi.it.
² Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via F Sforza 35, 20122, Milan, Italy. stocchet@policlinico.mi.it.
³ Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070, Brussels, Belgium. ftaccone@ulb.ac.be.
⁴ Department of Health Science, University of Milan-Bicocca, Ospedale San Gerardo, Via Pergolesi 33, 20900, Monza, MB, Italy. g.citerio@hsgerardo.org.
⁵ NeuroIntensive Care, Department of Emergency and Intensive Care, Ospedale San Gerardo, Via Pergolesi 33, 20900, Monza, MB, Italy. g.citerio@hsgerardo.org.
⁶ Department of Emergency Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-8579, USA. Paul.Pepe@UTSouthwestern.edu.
⁷ Department of Neurosurgery, Lankenau Medical Center, Wynnewood, PA, 19096, USA. LeRouxP@MLHS.ORG.
⁸ Department of Intensive Care Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) University Hospital, Faculty of Biology and Medicine, University of Lausanne, 1011, Lausanne, Switzerland. Mauro.Oddo@chuv.ch.
⁹ Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA. poldermankh@upmc.edu.
¹⁰ Division of Neuroscience Critical Care, Division of Adult Critical Care, Johns Hopkins Medicine, Baltimore, MD, 21287, USA. rstevens@jhmi.edu.
¹¹ NETT Clinical Coordinating Center, University of Michigan, Ann Arbor, MI, 48106-0381, USA. wbarsan@med.umich.edu.
¹² Department of Neurosurgery, University Hospital Antwerp and University of Antwerp, 2650, Edegem, Belgium. andrew.maas@uza.be.
¹³ Department of Intensive Care, UZ Leuven, Campus Gasthuisberg, 3000, Leuven, Belgium. geert.meyfroidt@uzleuven.be.
¹⁴ Department of Critical Care Medicine and the Safar Center for Resuscitation Research, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA. bellmj4@upmc.edu.
¹⁵ NETT Clinical Coordinating Center, University of Michigan, Ann Arbor, MI, 48106-0381, USA. robie@med.umich.edu.
¹⁶ Department of Neurocritical Care, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. PVespa@mednet.ucla.edu.
¹⁷ Center for Shock, Trauma & Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, MD, 21201, USA. afaden@anes.umm.edu.
¹⁸ Department of Neurology, Neurocritical Care Unit, Innsbruck Medical University, 6020, Innsbruck, Austria. raimund.helbok@uki.at.
¹⁹ Department of Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. tishermansa@ccm.upmc.edu.
²⁰ IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, 20156, Milan, Italy. elisa.zanier@marionegri.it.
²¹ Department of Emergency Medicine, University of Arizona, Tucson, AZ, 85724-5057, USA. hermanos.valenzuela@gmail.com.
²² Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. julia.wendon@kcl.ac.uk.
²³ Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. dkm13@wbic.cam.ac.uk.
²⁴ Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 1070, Brussels, Belgium. jlvincen@ulb.ac.be.

PMID: 25896893
PMCID: PMC4404577
DOI: 10.1186/s13054-015-0887-8

Abstract

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.

PubMed Disclaimer

Figures

**Figure 1**
**Neuroprotective strategies in the ICU.** To avoid further insults to the brain (NMR image of a normal brain at the center), the goals of intensive care management are to ensure adequate oxygen delivery and to avoid excessive oxygen consumption, as in epileptic crises and cases of high brain temperature. See text for details on reperfusion after ischemic stroke, optimal hemoglobin level, and desirable cerebral perfusion pressure (CPP) levels. ICP, intracranial pressure; MAP, mean arterial pressure; PaO₂, arterial oxygen tension.

See this image and copyright information in PMC

Cited by

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.
Hartings JA, Shuttleworth CW, Kirov SA, Ayata C, Hinzman JM, Foreman B, Andrew RD, Boutelle MG, Brennan KC, Carlson AP, Dahlem MA, Drenckhahn C, Dohmen C, Fabricius M, Farkas E, Feuerstein D, Graf R, Helbok R, Lauritzen M, Major S, Oliveira-Ferreira AI, Richter F, Rosenthal ES, Sakowitz OW, Sánchez-Porras R, Santos E, Schöll M, Strong AJ, Urbach A, Westover MB, Winkler MK, Witte OW, Woitzik J, Dreier JP. Hartings JA, et al. J Cereb Blood Flow Metab. 2017 May;37(5):1571-1594. doi: 10.1177/0271678X16654495. Epub 2016 Jan 1. J Cereb Blood Flow Metab. 2017. PMID: 27328690 Free PMC article. Review.
Serum biomarkers of delirium in the elderly: a narrative review.
Toft K, Tontsch J, Abdelhamid S, Steiner L, Siegemund M, Hollinger A. Toft K, et al. Ann Intensive Care. 2019 Jul 1;9(1):76. doi: 10.1186/s13613-019-0548-1. Ann Intensive Care. 2019. PMID: 31263968 Free PMC article. Review.
The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study.
Datzmann T, Messerer DAC, Münz F, Hoffmann A, Gröger M, Mathieu R, Mayer S, Gässler H, Zink F, McCook O, Merz T, Scheuerle A, Wolfschmitt EM, Thebrath T, Zuech S, Calzia E, Asfar P, Radermacher P, Kapapa T. Datzmann T, et al. Front Med (Lausanne). 2022 Aug 22;9:971882. doi: 10.3389/fmed.2022.971882. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36072939 Free PMC article.
The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome.
McDonald SJ, Sun M, Agoston DV, Shultz SR. McDonald SJ, et al. J Neuroinflammation. 2016 Apr 26;13(1):90. doi: 10.1186/s12974-016-0555-1. J Neuroinflammation. 2016. PMID: 27117191 Free PMC article. Review.
Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue.
Abu Hamdeh S, Shevchenko G, Mi J, Musunuri S, Bergquist J, Marklund N. Abu Hamdeh S, et al. Sci Rep. 2018 May 1;8(1):6807. doi: 10.1038/s41598-018-25060-0. Sci Rep. 2018. PMID: 29717219 Free PMC article.

See all "Cited by" articles

References

1. Selassie AW, Zaloshnja E, Langlois JA, Miller T, Jones P, Steiner C. Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J Head Trauma Rehabil. 2008;23:123–31. - PubMed
1. Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J. A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien). 2006;148:255–68. - PubMed
1. Roozenbeek B, Maas AI, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol. 2013;9:231–6. - PubMed
1. Hankey GJ. The global and regional burden of stroke. Lancet Glob Health. 2013;1:e239–40. - PubMed
1. Zacharia BE, Hickman ZL, Grobelny BT, DeRosa P, Kotchetkov I, Ducruet AF, et al. Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am. 2010;21:221–33. - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

U01 NS081041/NS/NINDS NIH HHS/United States

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Neuroprotection in acute brain injury: an up-to-date review

Affiliations

Neuroprotection in acute brain injury: an up-to-date review

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical