Brain Edema XVI pp 217-220 | Cite as
Intranasal Osteopontin for Rodent Germinal Matrix Hemorrhage
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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.
Keywords
Stroke, experimental Osteopontin Neonatal rats Germinal matrix hemorrhage Hydrocephalus Neurological dysfunctionNotes
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).
Disclosures
None
References
- 1.Ballabh P (2010) Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res 67:1–8PubMedCentralCrossRefPubMedGoogle 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 37:156–165CrossRefPubMedGoogle 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 5:586–594PubMedCentralCrossRefPubMedGoogle Scholar
- 5.Heron M, Sutton PD, Xu J, Ventura SJ, Strobino DM, Guyer B (2010) Annual summary of vital statistics: 2007. Pediatrics 125:4–15CrossRefPubMedGoogle Scholar
- 6.Uria-Avellanal C, Robertson NJ (2014) Na(+)/H(+) exchangers and intracellular pH in perinatal brain injury. Transl Stroke Res 5:79–98PubMedCentralCrossRefPubMedGoogle Scholar
- 7.Whitelaw A (2001) Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions. Semin Neonatol 6:135–146CrossRefPubMedGoogle 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 44:3189–3194PubMedCentralCrossRefPubMedGoogle 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 42:764–769PubMedCentralCrossRefPubMedGoogle Scholar
- 10.van Velthoven CT, Heijnen CJ, van Bel F, Kavelaars A (2011) Osteopontin enhances endogenous repair after neonatal hypoxic-ischemic brain injury. Stroke 42:2294CrossRefPubMedGoogle Scholar
- 11.Suzuki H, Hasegawa Y, Chen W, Kanamaru K, Zhang JH (2010) Recombinant osteopontin in cerebral vasospasm after subarachnoid hemorrhage. Ann Neurol 68:650–660PubMedCentralCrossRefPubMedGoogle 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 41:1783–1790PubMedCentralCrossRefPubMedGoogle 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 38:612–618PubMedCentralCrossRefPubMedGoogle 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 227:96–103PubMedCentralCrossRefPubMedGoogle 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 45:828–834PubMedCentralCrossRefPubMedGoogle 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 236:69–78PubMedCentralCrossRefPubMedGoogle 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 44:3587–3590PubMedCentralCrossRefPubMedGoogle Scholar
- 18.Thullier F, Lalonde R, Cousin X, Lestienne F (1997) Neurobehavioral evaluation of lurcher mutant mice during ontogeny. Brain Res Dev Brain Res 100:22–28CrossRefPubMedGoogle 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 PubMedGoogle 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 24:1133–1145CrossRefPubMedGoogle 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 28:2296–2302CrossRefPubMedGoogle 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 6:39–49CrossRefPubMedGoogle 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 5:618–626CrossRefPubMedGoogle Scholar
- 24.Tso MK, Macdonald RL (2014) Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit. Transl Stroke Res 5:174–189CrossRefPubMedGoogle 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 5:669–680CrossRefPubMedGoogle Scholar
- 26.Pluta RM, Bacher J, Skopets B, Hoffmann V (2014) A non-human primate model of aneurismal subarachnoid hemorrhage (SAH). Transl Stroke Res 5:681–691CrossRefPubMedGoogle Scholar
- 27.Zhang YP, Cai J, Shields LB, Liu N, Xu XM, Shields CB (2014) Traumatic brain injury using mouse models. Transl Stroke Res 5:454–471CrossRefPubMedGoogle 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 5:248–251PubMedCentralCrossRefPubMedGoogle Scholar