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Intranasal Osteopontin for Rodent Germinal Matrix Hemorrhage

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Book cover Brain Edema XVI

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 121))

Abstract

Germinal matrix hemorrhage (GMH) is the most common and devastating neurological problem of premature infants. Current treatment is largely ineffective and GMH has been nonpreventable. Osteopontin (OPN) is an endogenous protein that has been shown to be neuroprotective, however, it has not been tested in GMH. P7 neonatal rats were subjected to stereotactic ganglionic eminence collagenase infusion. Groups were as follows: (1) sham, (2) GMH + vehicle, (3) GMH + intranasal OPN. Seventy-two hours later, the animals were evaluated using righting reflex, blood-brain barrier (BBB) permeability by Evans blue dye leakage, brain water content, and hemoglobin assay. Intranasal OPN improved outcomes after GMH by attenuation of brain swelling, BBB function, re-bleeding, and neurological outcomes. OPN may play an important role in enhancing neuroprotective brain signaling following GMH. These observed effects may offer novel possibilities for therapy in this patient population.

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References

  1. Ballabh P (2010) Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res 67:1–8

    Article  PubMed Central  PubMed  Google Scholar 

  2. Aquilina K, Chakkarapani E, Love S, Thoresen M (2011) Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood. Neuropathol Appl Neurobiol 37:156–165

    Article  CAS  PubMed  Google Scholar 

  3. Chen Q, Zhang J, Guo J, Tang J, Tao Y, Li L, Feng H, Chen Z (2014) Chronic hydrocephalus and perihematomal tissue injury developed in a rat model of intracerebral hemorrhage with ventricular extension. Transl Stroke Res. doi:10.1007/s12975-014-0367-5

    Google Scholar 

  4. Zhao J, Chen Z, Xi G, Keep RF, Hua Y (2014) Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res 5:586–594

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Heron M, Sutton PD, Xu J, Ventura SJ, Strobino DM, Guyer B (2010) Annual summary of vital statistics: 2007. Pediatrics 125:4–15

    Article  PubMed  Google Scholar 

  6. Uria-Avellanal C, Robertson NJ (2014) Na(+)/H(+) exchangers and intracellular pH in perinatal brain injury. Transl Stroke Res 5:79–98

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Whitelaw A (2001) Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions. Semin Neonatol 6:135–146

    Article  CAS  PubMed  Google Scholar 

  8. Topkoru BC, Altay O, Duris K, Krafft PR, Yan J, Zhang JH (2013) Nasal administration of recombinant osteopontin attenuates early brain injury after subarachnoid hemorrhage. Stroke 44:3189–3194

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Chen W, Ma Q, Suzuki H, Hartman R, Tang J, Zhang JH (2011) Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model. Stroke 42:764–769

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. van Velthoven CT, Heijnen CJ, van Bel F, Kavelaars A (2011) Osteopontin enhances endogenous repair after neonatal hypoxic-ischemic brain injury. Stroke 42:2294

    Article  PubMed  Google Scholar 

  11. Suzuki H, Hasegawa Y, Chen W, Kanamaru K, Zhang JH (2010) Recombinant osteopontin in cerebral vasospasm after subarachnoid hemorrhage. Ann Neurol 68:650–660

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Suzuki H, Hasegawa Y, Kanamaru K, Zhang JH (2010) Mechanisms of osteopontin-induced stabilization of blood-brain barrier disruption after subarachnoid hemorrhage in rats. Stroke 41:1783–1790

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Suzuki H, Ayer R, Sugawara T, Chen W, Sozen T, Hasegawa Y, Kanamaru K, Zhang JH (2010) Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats. Crit Care Med 38:612–618

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Lekic T, Rolland W, Hartman R, Kamper J, Suzuki H, Tang J, Zhang JH (2011) Characterization of the brain injury, neurobehavioral profiles, and histopathology in a rat model of cerebellar hemorrhage. Exp Neurol 227:96–103

    Article  PubMed Central  PubMed  Google Scholar 

  15. Manaenko A, Lekic T, Barnhart M, Hartman R, Zhang JH (2014) Inhibition of transforming growth factor-beta attenuates brain injury and neurological deficits in a rat model of germinal matrix hemorrhage. Stroke 45:828–834

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Lekic T, Manaenko A, Rolland W, Krafft PR, Peters R, Hartman RE, Altay O, Tang J, Zhang JH (2012) Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus. Exp Neurol 236:69–78

    Article  PubMed Central  PubMed  Google Scholar 

  17. Leitzke AS, Rolland WB, Krafft PR, Lekic T, Klebe D, Flores JJ, Van Allen NR, Applegate RL 2nd, Zhang JH (2013) Isoflurane post-treatment ameliorates GMH-induced brain injury in neonatal rats. Stroke 44:3587–3590

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Thullier F, Lalonde R, Cousin X, Lestienne F (1997) Neurobehavioral evaluation of lurcher mutant mice during ontogeny. Brain Res Dev Brain Res 100:22–28

    Article  CAS  PubMed  Google Scholar 

  19. Schlunk F, Schulz E, Lauer A, Yigitkanli K, Pfeilschifter W, Steinmetz H, Lo EH, Foerch C (2014) Warfarin pretreatment reduces cell death and MMP-9 activity in experimental intracerebral hemorrhage. Transl Stroke Res. doi:10.1007/s12975-014-0377-3

    PubMed  Google Scholar 

  20. Tang J, Liu J, Zhou C, Alexander JS, Nanda A, Granger DN, Zhang JH (2004) Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. J Cereb Blood Flow Metab 24:1133–1145

    Article  PubMed  Google Scholar 

  21. Choudhri TF, Hoh BL, Solomon RA, Connolly ES Jr, Pinsky DJ (1997) Use of a spectrophotometric hemoglobin assay to objectively quantify intracerebral hemorrhage in mice. Stroke 28:2296–2302

    Article  CAS  PubMed  Google Scholar 

  22. Merali Z, Leung J, Mikulis D, Silver F, Kassner A (2014) Longitudinal assessment of imatinib’s effect on the blood-brain barrier after ischemia/reperfusion injury with permeability MRI. Transl Stroke Res 6:39–49

    Article  PubMed  Google Scholar 

  23. Li H, Gao A, Feng D, Wang Y, Zhang L, Cui Y, Li B, Wang Z, Chen G (2014) Evaluation of the protective potential of brain microvascular endothelial cell autophagy on blood-brain barrier integrity during experimental cerebral ischemia-reperfusion injury. Transl Stroke Res 5:618–626

    Article  PubMed  Google Scholar 

  24. Tso MK, Macdonald RL (2014) Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit. Transl Stroke Res 5:174–189

    Article  PubMed  Google Scholar 

  25. Marbacher S, Nevzati E, Croci D, Erhardt S, Muroi C, Jakob SM, Fandino J (2014) The rabbit shunt model of subarachnoid haemorrhage. Transl Stroke Res 5:669–680

    Article  CAS  PubMed  Google Scholar 

  26. Pluta RM, Bacher J, Skopets B, Hoffmann V (2014) A non-human primate model of aneurismal subarachnoid hemorrhage (SAH). Transl Stroke Res 5:681–691

    Article  PubMed  Google Scholar 

  27. Zhang YP, Cai J, Shields LB, Liu N, Xu XM, Shields CB (2014) Traumatic brain injury using mouse models. Transl Stroke Res 5:454–471

    Article  PubMed  Google Scholar 

  28. Wada K, Makino H, Shimada K, Shikata F, Kuwabara A, Hashimoto T (2014) Translational research using a mouse model of intracranial aneurysm. Transl Stroke Res 5:248–251

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgment

This study was partially supported by the National Institutes of Health grant RO1 NS078755 (Dr. Zhang) and American Heart Association CRP 17380009 (Dr. Lekic).

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Authors and Affiliations

  1. Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA

    Jay Malaguit, Brandon Dixon, Desislava Doycheva, Jiping Tang, John H. Zhang & Tim Lekic MD, PhD

  2. Departments of Neonatology, School of Medicine, Loma Linda, CA, USA

    Darlene Casel

  3. Neurosurgery, School of Medicine, Loma Linda, CA, USA

    John H. Zhang

  4. Department of Physiology, Loma Linda University School of Medicine, 11041 Campus Street, Risley Hall Rm 129, Loma Linda, CA, 92354, USA

    Tim Lekic MD, PhD

Authors
  1. Jay Malaguit
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  2. Darlene Casel
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  3. Brandon Dixon
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  4. Desislava Doycheva
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  5. Jiping Tang
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  6. John H. Zhang
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  7. Tim Lekic MD, PhD
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Corresponding author

Correspondence to Tim Lekic MD, PhD .

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Editors and Affiliations

  1. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Richard L. Applegate

  2. Department of Neurosurgery, Soochow University The First Affiliated Hospital, Suzhou, Jiangsu, China

    Gang Chen

  3. Department of Neurosurgery, Third Military Medical University Southwest Hospital, Chongqing, China

    Hua Feng

  4. Dept.of Anesthesiology, Physiology and Neurosurgery, Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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© 2016 Springer International Publishing Switzerland

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Malaguit, J. et al. (2016). Intranasal Osteopontin for Rodent Germinal Matrix Hemorrhage. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_39

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  • DOI: https://doi.org/10.1007/978-3-319-18497-5_39

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-18496-8

  • Online ISBN: 978-3-319-18497-5

  • eBook Packages: MedicineMedicine (R0)

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