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Neuroprotective Strategies in Hemorrhagic Stroke

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Translational Research in Stroke

Part of the book series: Translational Medicine Research ((TRAMERE))

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Abstract

Hemorrhagic stroke is a devastating disease that represents 10–15% of all strokes in the United States, with high rates of morbidity and mortality. Primary injury to the brain is caused by disruption of the neuronal network, while secondary injury correlates with neuroinflammation, cellular lysis, and perihematomal edema. An approach targeting primary injury involves the evacuation of the intraparenchymal hematoma, which has shown mixed results depending on the invasiveness of the approach. Various neuroprotective strategies have been employed to prevent neuronal damage. Both intraparenchymal and subarachnoid hemorrhages are associated with significant neuroinflammation. Anti-inflammatory pharmacological interventions, such as heparin and glyburide, show significant promise in decreasing the extent of the delayed neurological damage. Other strategies have focused on targeting mitochondria and the final steps of neuronal apoptosis with minocycline, which has showed significant promise in all stroke types. Hemorrhagic stroke remains a devastating disease, and more neuroprotective strategies are needed to maximize the available therapeutic interventions and their effectiveness.

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Abbreviations

ASTROH:

Aneurysmal Subarachnoid Hemorrhage Trial Randomizing Heparin

BBB:

Blood-brain barrier

CLEAR:

Clot Lysis Evaluation of Accelerated Resolution of IVH

EGFR:

Epidermal growth factor receptor

ENRICH:

Early Minimally Invasive Removal of Intracerebral Hemorrhage

ET-1:

Endothelin-1

EVD:

External ventricular drain

GATA-1:

Erythroid transcription factor

ICAM-1:

Intercellular adhesion molecule-1

ICH:

Intracerebral hemorrhage

IVH:

Intraventricular hemorrhage

MAC:

Membrane attack complex

MACH:

Minocycline in Intracerebral Hemorrhage Patients

MISTIE:

Minimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage Evacuation

MMPs:

Matrix metalloproteinases

MPO:

Myeloperoxidase

rt-PA:

Recombinant tissue plasminogen activator

SAH:

Subarachnoid hemorrhage

SLEUTH:

Stereotactic approaches associated with ultrasound-mediated lysis of the clot

STICH II:

Surgical Trial in Lobar Intracerebral Hemorrhage

STICH:

Surgical Trial in Intracerebral Hemorrhage

SUR1:

Sulfonylurea receptor-1

TNF-α:

Tumor necrosis factor-α

Trpm4:

Transient receptor potential melastatin 4

UFH:

Unfractionated heparin

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Disclosures

RFJ is the national primary principal investigator for ASTROH. JMS is the national co-principal investigator for ASTROH. The authors declare no other conflicts of interest related to this work. RFJ is supported by grants from the Brain Aneurysm Foundation, MicroVention, Inc., Penumbra, Inc., and Medtronic, Inc. JMS is supported by grants from the National Institute of Neurological Disorders and Stroke (NS060801; NS061808) and the National Heart, Lung, and Blood Institute (HL082517).

Author Contributions

Conception and design: James, Williams, Khattar; review of the literature: Khattar, James; drafting of the manuscript: Khattar; critically revising the manuscript: all authors; supervision of project: Williams, James

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Author notes

  1. Brian J. Williams and Robert F. James are contributed equally as senior co-authors

Authors and Affiliations

  1. Department of Neurological Surgery, University of Louisville School of Medicine, 220 Abraham Flexner way, Suite 1531, Louisville, KY, 40202, USA

    Nicolas K. Khattar, Brian J. Williams & Robert F. James

  2. Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA

    Dale Ding

  3. Departments of Neurosurgery, Pathology and Physiology, University of Maryland School of Medicine, Baltimore, MD, USA

    J. Marc Simard

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  1. Nicolas K. Khattar
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Corresponding author

Correspondence to Robert F. James .

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Editors and Affiliations

  1. Department of Neurology & Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, California, USA

    Paul A. Lapchak

  2. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Guo-Yuan Yang

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Khattar, N.K., Williams, B.J., Ding, D., Marc Simard, J., James, R.F. (2017). Neuroprotective Strategies in Hemorrhagic Stroke. In: Lapchak, P., Yang, GY. (eds) Translational Research in Stroke. Translational Medicine Research. Springer, Singapore. https://doi.org/10.1007/978-981-10-5804-2_22

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