Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury

  • Lei Huang
  • Wendy Woo
  • Prativa Sherchan
  • Nikan H. Khatibi
  • Paul Krafft
  • William Rolland
  • Richard L. ApplegateII
  • Robert D. Martin
  • John Zhang
Chapter
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 121)

Abstract

Surgically induced brain injury (SBI) results in brain edema and neurological decline. Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases. In this study, we investigated the pretreatment effect of VA in a rat model of SBI. A total of 57 male Sprague-Dawley rats were use in four groups: sham, SBI + vehicle, SBI + low dose (100 mg/kg) VA, and SBI + high dose (300 mg/kg) VA. SBI was induced by partially resecting right frontal lobes. Shams underwent identical surgical procedures without brain resection. VA or vehicle was administered subcutaneously 30 min prior to SBI. At 24 and 72 h post SBI, neurobehavior and brain water content were assessed as well as matrix metalloproteinases (MMPs) activities. There was significantly higher brain water content within the right frontal lobe in SBI rats than in shams. Without neurobehavioral improvements, the low-dose but not high-dose VA significantly reduced brain edema at 24 h post SBI. The protection tends to persist to 72 h post SBI. At 24 h post SBI, low-dose VA did not significantly reduce the elevated MMP-9 activity associated with SBI. In conclusion, VA pretreatment attenuated brain edema at 24 h after SBI but lacked MMP inhibition. The single dose VA was not associated with neurobehavioral benefits.

Keywords

Surgically induced brain injury Water content Neurobehavior Matrix metalloproteinases 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This study is partially supported by grants from National Institute of Health (NIH) NS081740, NS043338 to J. Zhang.

Conflict of Interest Statement

All authors have no conflicts of interest to disclose.

References

  1. 1.
    Andrews RJ, Muto RP (1992) Retraction brain ischaemia: cerebral blood flow, evoked potentials, hypotension and hyperventilation in a new animal model. Neurol Res 14:12–18PubMedGoogle Scholar
  2. 2.
    Aoki T, Sumii T, Mori T, Wang X, Lo EH (2002) Blood–brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke 33:2711–2717CrossRefPubMedGoogle Scholar
  3. 3.
    Badaut J, Bix GJ (2014) Vascular neural network phenotypic transformation after traumatic injury: potential role in long-term sequelae. Transl Stroke Res 5:394–406PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Dash PK, Orsi SA, Zhang M, Grill RJ, Pati S, Zhao J, Moore AN (2010) Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PLoS One 5:e11383PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH (2001) Matrix metalloproteinase inhibition prevents oxidative stress-associated blood–brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21:1393–1400CrossRefPubMedGoogle Scholar
  6. 6.
    Hellwig D, Bertalanffy H, Bauer BL, Tirakotai W (2003) Pontine hemorrhage. J Neurosurg 99:796; author reply 796–797PubMedGoogle Scholar
  7. 7.
    Jadhav V, Matchett G, Hsu FPK, Zhang JH (2007) Inhibition of Src tyrosine kinase and effect on outcomes in a new in vivo model of surgically induced brain injury. J Neurosurg 106:680–686CrossRefPubMedGoogle Scholar
  8. 8.
    Khanna A, Kahle KT, Walcott BP, Gerzanich V, Simard JM (2014) Disruption of ion homeostasis in the neurogliovascular unit underlies the pathogenesis of ischemic cerebral edema. Transl Stroke Res 5:3–16PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Marmarou A, Signoretti S, Aygok G, Fatouros P, Portella G (2006) Traumatic brain edema in diffuse and focal injury: cellular or vasogenic? Acta Neurochir Suppl 96:24–29CrossRefPubMedGoogle Scholar
  10. 10.
    Matchett G, Hahn J, Obenaus A, Zhang J (2006) Surgically induced brain injury in rats: the effect of erythropoietin. J Neurosci Methods 158:234–241CrossRefPubMedGoogle Scholar
  11. 11.
    Pennypacker KR (2014) Targeting the peripheral inflammatory response to stroke: role of the spleen. Transl Stroke Res 5:635–637CrossRefPubMedGoogle Scholar
  12. 12.
    Qian YR, Lee MJ, Hwang S, Kook JH, Kim JK, Bae CS (2010) Neuroprotection by valproic acid in mouse models of permanent and transient focal cerebral ischemia. Korean J Physiol Pharmacol 14:435–440PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC (1998) Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke 29:1020–1030CrossRefPubMedGoogle Scholar
  14. 14.
    Seifert HA, Pennypacker KR (2014) Molecular and cellular immune responses to ischemic brain injury. Transl Stroke Res 5:543–553PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Sinn DI, Kim SJ, Chu K, Jung KH, Lee ST, Song EC, Kim JM, Park DK, Kun Lee S, Kim M, Roh JK (2007) Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol Dis 26:464–472CrossRefPubMedGoogle Scholar
  16. 16.
    Solaroglu I, Beskonakli E, Kaptanoglu E, Okutan O, Ak F, Taskin Y (2004) Transcortical-transventricular approach in colloid cysts of the third ventricle: surgical experience with 26 cases. Neurosurg Rev 27:89–92CrossRefPubMedGoogle Scholar
  17. 17.
    Suda S, Katsura KI, Kanamaru T, Saito M, Katayama Y (2013) Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation. Eur J Pharmacol 707:26–31CrossRefPubMedGoogle Scholar
  18. 18.
    Wang Z, Leng Y, Tsai LK, Leeds P, Chuang DM (2011) Valproic acid attenuates blood–brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. J Cereb Blood Flow Metab 31:52–57PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Xuan A, Long D, Li J, Ji W, Hong L, Zhang M, Zhang W (2012) Neuroprotective effects of valproic acid following transient global ischemia in rats. Life Sci 90:463–468CrossRefPubMedGoogle Scholar
  20. 20.
    Yamaguchi M, Jadhav V, Obenaus A, Colohan A, Zhang JH (2007) Matrix metalloproteinase inhibition attenuates brain edema in an in vivo model of surgically-induced brain injury. Neurosurgery 61:1067–1075CrossRefPubMedGoogle Scholar
  21. 21.
    Zhao X, Sun G, Zhang H, Ting SM, Song S, Gonzales N, Aronowski J (2014) Polymorphonuclear neutrophil in brain parenchyma after experimental intracerebral hemorrhage. Transl Stroke Res 5:554–561CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Lei Huang
    • 1
    • 2
  • Wendy Woo
    • 2
  • Prativa Sherchan
    • 2
  • Nikan H. Khatibi
    • 1
  • Paul Krafft
    • 2
  • William Rolland
    • 2
  • Richard L. ApplegateII
    • 1
  • Robert D. Martin
    • 1
  • John Zhang
    • 1
    • 2
    • 3
  1. 1.Department of AnesthesiologyLoma Linda UniversityLoma LindaUSA
  2. 2.Division of Physiology, Department of Basic ScienceLoma Linda UniversityLoma LindaUSA
  3. 3.Department of NeurosurgeryLoma Linda UniversityLoma LindaUSA

Personalised recommendations