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Open Access Review

The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies

Elke Kooijman12, Cora H Nijboer2, Cindy TJ van Velthoven2, Annemieke Kavelaars3, Jozef Kesecioglu1 and Cobi J Heijnen3*

Author Affiliations

1 Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

2 Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands

3 Division of Internal Medicine, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Journal of Neuroinflammation 2014, 11:2  doi:10.1186/1742-2094-11-2

Published: 3 January 2014

Abstract

Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed.

SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH.

Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult.

Keywords:
Cell death; Endovascular puncture; Inflammation; Neuroregeneration; Stem cells; Subarachnoid hemorrhage; Treatment options