Skip to main content

Advertisement

Springer Nature Link
Log in

Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice

  • Research Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Traumatic brain injury (TBI) is accompanied with enhanced matrix metalloproteinase-9 (MMP-9) activity and elevated levels of plasma fibrinogen (Fg), which is a known inflammatory agent. Activation of MMP-9 and increase in blood content of Fg (i.e. hyperfibrinogenemia, HFg) both contribute to cerebrovascular disorders leading to blood brain barrier disruption. It is well-known that activation of MMP-9 contributes to vascular permeability. It has been shown that at an elevated level (i.e. HFg) Fg disrupts blood brain barrier. However, mechanisms of their actions during TBI are not known. Mild TBI was induced in wild type (WT, C57BL/6 J) and MMP-9 gene knockout (Mmp9−/−) homozygous, mice. Pial venular permeability to fluorescein isothiocyanate-conjugated bovine serum albumin in pericontusional area was observed 14 days after injury. Mice memory was tested with a novel object recognition test. Increased expression of Fg endothelial receptor intercellular adhesion protein-1 and formation of caveolae were associated with enhanced activity of MMP-9 causing an increase in pial venular permeability. As a result, an enhanced deposition of Fg and cellular prion protein (PrPC) were found in pericontusional area. These changes were attenuated in Mmp9−/− mice and were associated with lesser loss of short-term memory in these mice than in WT mice. Our data suggest that mild TBI-induced increased cerebrovascular permeability enhances deposition of Fg-PrPC and loss of memory, which is ameliorated in the absence of MMP-9 activity. Thus, targeting MMP-9 activity and blood level of Fg can be a possible therapeutic remedy to diminish vasculo-neuronal damage after TBI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Adams RA, Bauer J, Flick MJ, Sikorski SL, Nuriel T, Lassmann H, Degen JL, Akassoglou K (2007) The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J Exp Med 204(3):571–582. doi:10.1084/jem.20061931

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ahn HJ, Zamolodchikov D, Cortes-Canteli M, Norris EH, Glickman JF, Strickland S (2010) Alzheimer’s disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci 107(50):21812–21817. doi:10.1073/pnas.1010373107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Altieri DC, Duperray A, Plescia J, Thornton GB, Languino LR (1995) Structural recognition of a novel fibrinogen gamma chain sequence (117–133) by intercellular adhesion molecule-1 mediates leukocyte-endothelium interaction. J Biol Chem 270(2):696–699

    Article  CAS  PubMed  Google Scholar 

  • Bevins RA, Besheer J (2006) Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protocols 1 (3):1,306–1,311. doi:http://www.nature.com/nprot/journal/v1/n3/suppinfo/nprot.2006.205_S1.html

  • Carson-Walter E, Hampton J, Shue E, Geynisman D, Pillai P, Sathanoori R, Madden S, Hamilton R, Walter K (2005) Plasmalemmal vesicle associated protein-1 is a novel marker implicated in brain tumor angiogenesis. Clin Cancer Res 11(21):7643–7650

    Article  CAS  PubMed  Google Scholar 

  • Cernich A, Kurtz S, Mordecai K, Ryan P (2010) Cognitive rehabilitation in traumatic brain injury. Curr Treat Options Neurol 12(5):412–423. doi:10.1007/s11940-010-0085-6

    Article  PubMed  Google Scholar 

  • Chhabra G, Rangarajan K, Subramanian A, Agrawal D, Sharma S, Mukhopadhayay A (2010) Hypofibrinogenemia in isolated traumatic brain injury in Indian patients. Neurol India 58(5):756–757. doi:10.4103/0028-3886.72175

    Article  PubMed  Google Scholar 

  • Choo AM, Miller WJ, Chen Y-C, Nibley P, Patel TP, Goletiani C, Morrison B, Kutzing MK, Firestein BL, Sul J-Y, Haydon PG, Meaney DF (2013) Antagonism of purinergic signalling improves recovery from traumatic brain injury. Brain. doi:10.1093/brain/aws286

    PubMed Central  PubMed  Google Scholar 

  • Chung E, Ji Y, Sun Y, Kascsak R, Kascsak R, Mehta P, Strittmatter S, Wisniewski T (2010) Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer’s disease model mouse. BMC Neurosci 11:130. doi:10.1186/1471-2202-11-130

    Article  PubMed Central  PubMed  Google Scholar 

  • Cohen ZVI, Bonvento G, Lacombe P, Hamel E (1996) Serotonin in the regulation of brain microcirculation. Prog Neurobiol 50(4):335–362. doi:10.1016/s0301-0082(96)00033-0

    Article  CAS  PubMed  Google Scholar 

  • D’Erasmo E, Acca M, Celi FS, Medici F, Palmerini T, Pisani D (1993) Plasma fibrinogen and platelet count in stroke. J Med 24(2–3):185–191

    PubMed  Google Scholar 

  • Davalos D, Akassoglou K (2012) Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 34(1):43–62

    Article  CAS  PubMed  Google Scholar 

  • Davalos D, Kyu Ryu J, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K (2012) Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 3:1,227. doi:http://www.nature.com/ncomms/journal/v3/n11/suppinfo/ncomms2230_S1.html

  • del Zoppo GJ, Levy DE, Wasiewski WW, Pancioli AM, Demchuk AM, Trammel J, Demaerschalk BM, Kaste M, Albers GW, Ringelstein EB (2009) Hyperfibrinogenemia and functional outcome from acute ischemic stroke. Stroke 40(5):1687–1691. doi:10.1161/strokeaha.108.527804

    Article  PubMed Central  PubMed  Google Scholar 

  • Ernst E, Resch KL (1993) Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med 118:956–963

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Patron C, Zouki C, Whittal R, Chan JS, Davidge ST, Filep JG (2001) Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1 [1–32]. FASEB J 15(12):2230–2240

    Article  CAS  PubMed  Google Scholar 

  • Fischer MB, Roeckl C, Parizek P, Schwarz HP, Aguzzi A (2000) Binding of disease-associated prion protein to plasminogen. Nature 408(6811):479–483

    Article  CAS  PubMed  Google Scholar 

  • Flick MJ, Du X, Witte DP, Jirouskova M, Soloviev DA, Busuttil SJ, Plow EF, Degen JL (2004) Leukocyte engagement of fibrin (ogen) via the integrin receptor αMβ2/Mac-1 is critical for host inflammatory response in vivo. J Clin Invest 113(11):1596–1606. doi:10.1172/JCI20741

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Laurén J, Gimbel ZA, Strittmatter SM (2010) Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neuroradiol 30(18):6367–6374. doi:10.1523/jneurosci.0395-10.2010

    CAS  Google Scholar 

  • Granger D, Senchenkova E (2010) Inflammation and the Microcirculation. Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease. Morgan & Claypool Life Sciences, San Rafael

    Google Scholar 

  • Grossetete M, Phelps J, Arko L, Yonas H, Rosenberg G (2009) Elevation of matrix metalloproteinases 3 and 9 in cerebrospinal fluid and blood in patients with severe traumatic brain injury. Neurosurgery 65(4):702–708

    Article  PubMed Central  PubMed  Google Scholar 

  • Hadass O, Tomlinson BN, Gooyit M, Chen S, Purdy JJ, Walker JM, Zhang C, Giritharan AB, Purnell W, Robinson CR II, Shin D, Schroeder VA, Suckow MA, Simonyi AY, Sun G, Mobashery S, Cui J, Chang M, Gu Z (2013) Selective inhibition of matrix metalloproteinase-9 attenuates secondary damage resulting from severe traumatic brain injury. PLoS One 8(10):e76904. doi:10.1371/journal.pone.0076904

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hnasko R, McFarland M, Ben-Jonathan N (2002) Distribution and characterization of plasmalemma vesicle protein-1 in rat endocrine glands. J Endocrinol 175(3):649–661. doi:10.1677/joe.0.1750649

    Article  CAS  PubMed  Google Scholar 

  • Hu G, Vogel SM, Schwartz DE, Malik AB, Minshall RD (2008) Intercellular Adhesion Molecule-1–Dependent Neutrophil Adhesion to Endothelial Cells Induces Caveolae-Mediated Pulmonary Vascular Hyperpermeability. Circ Res 102(12):e120–e131. doi:10.1161/circresaha.107.167486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Johnson VE, Stewart W, Smith DH (2010) Traumatic brain injury and amyloid-[beta] pathology: a link to Alzheimer’s disease? Nat Rev Neurosci 11(5):361–370

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kerlin B, Cooley BC, Isermann BH, Hernandez I, Sood R, Zogg M, Hendrickson SB, Mosesson MW, Lord S, Weiler H (2004) Cause-effect relation between hyperfibrinogenemia and vascular disease. Curr Opin Hematol 103(5):1728–1734

    CAS  Google Scholar 

  • Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-[bgr] oligomers. Nature 457 (7233):1,128–1,132. doi:http://www.nature.com/nature/journal/v457/n7233/suppinfo/nature07761_S1.html

  • Letcher RL, Chien S, Pickering TG, Sealey JE, Laragh JH (1981) Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects. Role of fibrinogen and concentration. Am J Med 70:1195–1202

    Article  CAS  PubMed  Google Scholar 

  • Lishko VK, Kudryk B, Yakubenko VP, Yee VC, Ugarova TP (2002) Regulated unmasking of the cryptic binding site foriIntegrin αMβ2 in the γC-domain of fibrinogen. Biochemistry 41(43):12942–12951. doi:10.1021/bi026324c

    Article  CAS  PubMed  Google Scholar 

  • Lominadze D, Joshua IG, Schuschke DA (1998) Increased erythrocyte aggregation in spontaneously hypertensive rats. Am J Hypertens 11:784–789

    Article  CAS  PubMed  Google Scholar 

  • Lominadze D, Tsakadze N, Sen U, Falcone JC, D’Souza SE (2005) Fibrinogen- and fragment D-induced vascular constriction. Am J Physiol 288(3):H1257–H1264

    CAS  Google Scholar 

  • Lominadze D, Roberts AM, Tyagi N, Tyagi SC (2006) Homocysteine causes cerebrovascular leakage in mice. Am J Physiol Heart Circ Physiol 290(3):H1206–H1213

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lominadze D, Dean WL, Tyagi SC, Roberts AM (2010) Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease. Acta Physiol 198(1):1–13

    Article  CAS  Google Scholar 

  • Lyon L, Saksida L, Bussey T (2012) Spontaneous object recognition and its relevance to schizophrenia: a review of findings from pharmacological, genetic, lesion and developmental rodent models. Psychopharmacology 220(4):647–672. doi:10.1007/s00213-011-2536-5

    Article  CAS  PubMed  Google Scholar 

  • Mansoor O, Cayol M, Gachon P, Boirie Y, Schoeffler P, Obled C, Beaufrère B (1997) Albumin and fibrinogen syntheses increase while muscle protein synthesis decreases in head-injured patients. Am J Physiol Endocrinol Metab 273(5):E898–E902

    CAS  Google Scholar 

  • Mehta D, Malik AB (2006) Signaling mechanisms regulating endothelial permeability. Physiol Rev 86(1):279–367

    Article  CAS  PubMed  Google Scholar 

  • Minshall RD, Tiruppathi C, Vogel SM, Niles WD, Gilchrist A, Hamm HE, Malik AB (2000) Endothelial cell-surface gp60 activates vesicle formation and trafficking via G(i)-coupled Src kinase signaling pathway. J Cell Biol 150(5):1057–1070

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mori T, Wang X, Aoki T, Lo EH (2002) Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury. J Neurotrauma 19(11):1411–1419. doi:10.1089/089771502320914642

    Article  PubMed  Google Scholar 

  • Mozer A, Whittemore S, Benton R (2010) Spinal microvascular expression of PV-1 is associated with inflammation, perivascular astrocyte loss, and diminished EC glucose transport potential in acute SCI. Curr Neurovasc Res 7(3):238–250

    Article  CAS  PubMed  Google Scholar 

  • Muradashvili N, Lominadz D (2013) Role of fibrinogen in cerebrovascular dysfunction after traumatic brain injury. Brain Inj 27(13–14):1508–1515. doi:10.3109/02699052.2013.823562

    Article  PubMed Central  PubMed  Google Scholar 

  • Muradashvili N, Tyagi N, Tyagi R, Munjal C, Lominadze D (2011) Fibrinogen alters mouse brain endothelial cell layer integrity affecting vascular endothelial cadherin. Biochem Biophys Res Commun 413(4):509–514. doi:10.1016/j.bbrc.2011.07.133

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Muradashvili N, Qipshidze N, Munjal C, Givvimani S, Benton RL, Roberts AM, Tyagi SC, Lominadze D (2012a) Fibrinogen-induced increased pial venular permeability in mice. J Cereb Blood Flow Metab 32(1):150–163. doi:10.1038/jcbfm.2011.144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Muradashvili N, Tyagi R, Lominadze D (2012b) A dual-tracer method for differentiating transendothelial transport from paracellular leakage in vivo and in vitro. Front Physiol 3:166–172. doi:10.3389/fphys.2012.00166

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Muradashvili N, Benton R, Tyagi S, Lominadz D (2013) Elevated level of fibrinogen increases caveolae formation; Role of matrix metalloproteinase-9. Cell Biochemistry and Biophysics: [Epub ahead of print]

  • Pahatouridis D, Alexiou G, Zigouris A, Mihos E, Drosos D, Voulgaris S (2010) Coagulopathy in moderate head injury. The role of early administration of low molecular weight heparin. Brain Inj 24(10):1189–1192

    Article  PubMed  Google Scholar 

  • Parton RG, Joggerst B, Simons K (1994) Regulated internalization of caveolae. J Cell Biol 127(5):1199–1215. doi:10.1083/jcb.127.5.1199

    Article  CAS  PubMed  Google Scholar 

  • Patibandla PK, Tyagi N, Dean WL, Tyagi SC, Roberts AM, Lominadze D (2009) Fibrinogen induces alterations of endothelial cell tight junction proteins. J Cell Physiol 221(1):195–203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Phillips PG, Birnby LM (2004) Nitric oxide modulates caveolin-1 and matrix metalloproteinase-9 expression and distribution at the endothelial cell/tumor cell interface. Am J Physiol Lung Cell Mol Physiol 286(5):L1055–L1065. doi:10.1152/ajplung.00262.2003

    Article  CAS  PubMed  Google Scholar 

  • Pleasant J, Carlson S, Mao H, Scheff S, Yang K, Saatman K (2011) Rate of neurodegeneration in the mouse controlled cortical impact model is influenced by impactor tip shape: implications for mechanistic and therapeutic studies. Journal of Neurotrauma

  • Plow EF, Haas TA, Zhang L, Loftus J, Smith JW (2000) Ligand binding to integrins. J Biol Chem 275(29):21785–21788

    Article  CAS  PubMed  Google Scholar 

  • Rosell A, Alvarez-Sabin J, Arenillas JF, Rovira A, Delgado P, Fernandez-Cadenas I, Penalba A, Molina CA, Montaner J (2005) A matrix metalloproteinase protein array reveals a strong relation between MMP-9 and MMP-13 with diffusion-weighted image lesion increase in human stroke. Stroke 36(7):1415–1420

    Article  CAS  PubMed  Google Scholar 

  • Rosell A, Ortega-Aznar A, Alvarez-Sabin J, Fernandez-Cadenas I, Ribo M, Molina CA, Lo EH, Montaner J (2006) Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke. Stroke 37(6):1399–1406

    Article  CAS  PubMed  Google Scholar 

  • Ross R (1999) Mechanisms of disease - Atherosclerosis - An inflammatory disease. N Engl J Med 340(2):115–126

    Article  CAS  PubMed  Google Scholar 

  • Rybarczyk BJ, Lawrence SO, Simpson-Haidaris PJ (2003) Matrix-fibrinogen enhances wound closure by increasing both cell proliferation and migration. Blood 102(12):4035–4043. doi:10.1182/blood-2003-03-0822

    Article  CAS  PubMed  Google Scholar 

  • Sahni A, Arévalo MT, Sahni SK, Simpson-Haidaris PJ (2009) The VE-cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells. Int J Cancer 125(3):577–584

    Article  CAS  PubMed  Google Scholar 

  • Sangiorgi S, De Benedictis A, Protasoni M, Manelli A, Reguzzoni M, Cividini A, Dell’Orbo C, Tomei G, Balbi S (2013) Early-stage microvascular alterations of a new model of controlled cortical traumatic brain injury: 3D morphological analysis using scanning electron microscopy and corrosion casting. J Neurosurg 118(4):763–774. doi:10.3171/2012.11.JNS12627

    Article  PubMed  Google Scholar 

  • Schwarzmaier S, Kim S, Trabold R, Plesnila N (2010) Temporal profile of thrombogenesis in the cerebral microcirculation after traumatic brain injury in mice. J Neurotrauma 27(1):121–130

    Article  PubMed  Google Scholar 

  • Sen U, Tyagi N, Patibandla PK, Dean WL, Tyagi SC, Roberts AM, Lominadze D (2009) Fibrinogen-induced endothelin-1 production from endothelial cells. AJP - Cell Physiol 296(4):C840–C847

    Article  CAS  Google Scholar 

  • Shigemori Y, Katayama Y, Mori T, Maeda T, Kawamata T (2006) Matrix metalloproteinase-9 is associated with blood–brain barrier opening and brain edema formation after cortical contusion in rats. In: Hoff JT, Keep RF, Xi G, Hua Y (eds) Brain Edema XIII, vol 96. Acta Neurochirurgica Supplement vol Supplement 96. Springer, Wien, pp 130–133

    Google Scholar 

  • Shlosberg D, Benifla M, Kaufer D, Friedman A (2010) Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol 6(7):393–403

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shue E, Carson-Walter E, Liu Y, Winans B, Ali Z, Chen J, Walter K (2008) Plasmalemmal vesicle associated protein-1 (PV-1) is a marker of blood–brain barrier disruption in rodent models. BMC Neurosci 9(1):29

    Article  PubMed Central  PubMed  Google Scholar 

  • Simionescu M, Popov D, Sima A (2009) Endothelial transcytosis in health and disease. Cell Tissue Res 335(1):27–40. doi:10.1007/s00441-008-0688-3

    Article  PubMed  Google Scholar 

  • Stan R-V, Marion K, Palade GE (1999) PV-1 is a component of the fenestral and stomatal diaphragms in fenestrated endothelia. Proc Natl Acad Sci U S A 96(23):13203–13207

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sun Y, Hu G, Zhang X, Minshall RD (2009) Phosphorylation of Caveolin-1 Regulates Oxidant–Induced Pulmonary Vascular Permeability via Paracellular and Transcellular Pathways. Circ Res 105(7):676–685. doi:10.1161/circresaha.109.201673

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sun Y, Wang J, Wu X, Xi C, Gai Y, Liu H, Yuan Q, Wang E, Gao L, Hu J, Zhou L (2011) Validating the incidence of coagulopathy and disseminated intravascular coagulation in patients with traumatic brain injury – analysis of 242 cases. Br J Neurosurg 25(3):363–368. doi:10.3109/02688697.2011.552650

    Article  PubMed  Google Scholar 

  • Tran HT, LaFerla FM, Holtzman DM, Brody DL (2011) Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal aAmyloid-β accumulation and independently accelerates the development of Tau abnormalities. J Neurosci 31(26):9513–9525. doi:10.1523/jneurosci.0858-11.2011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tyagi N, Roberts AM, Dean WL, Tyagi SC, Lominadze D (2008) Fibrinogen induces endothelial cell permeability. Mol Cell Biochem 307(1–2):13–22

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, Dixon CE, Fini ME, Lo EH (2000) Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20(18):7037–7042

    CAS  PubMed  Google Scholar 

  • Wei E, Hamm R, Baranova A, Povlishock J (2009) The long-term microvascular and behavioral consequences of experimental traumatic brain injury after hypothermic intervention. J Neurotrauma 26(4):527–537

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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(5):1067–1076, 1010.1227/1001.neu.0000303203.0000307866.0000303218

    Article  PubMed  Google Scholar 

  • Yu J, Bergaya S, Murata T, Alp IF, Bauer MP, Lin MI, Drab M, Kurzchalia TV, Stan RV, Sessa WC (2006) Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J Clin Investig 116(5):1284. doi:10.1172/jci27100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang R, Yang D, Zhou C, Cheng K, Liu Z, Chen L, Fang L, Xie P (2012) β-Actin as a loading control for plasma-based Western blot analysis of major depressive disorder patients. Anal Biochem 427(2):116–120. doi:10.1016/j.ab.2012.05.008

    Article  CAS  PubMed  Google Scholar 

  • Zlokovic BV, Griffin JH (2011) Cytoprotective protein C pathways and implications for stroke and neurological disorders. Trends Neurosci 34(4):198–209. doi:10.1016/j.tins.2011.01.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported in part by NIH grants P30 GM-103507 (Pilot Project to D.L.), NS-084823 (to D.L. and S.C.T.), and NS-051568 (to S.C.T.)

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA

    Nino Muradashvili, Suresh C. Tyagi & David Lominadze

  2. Department of Anatomical Sciences and Neurobiology and Kentucky Spinal Cord Injury Research Center (KSCIRC), School of Medicine, University of Louisville, Louisville, KY, USA

    Richard L. Benton

  3. Department of Physiology and Neurosurgery and Spinal Cord & Brain Injury Research Center (SCoBIRC), University of Kentucky, Lexington, KY, USA

    Kathryn E. Saatman

  4. Department of Physiology & Biophysics, School of Medicine, University of Louisville, Bldg. A, Room 1115, 500 South Preston Street, Louisville, KY, 40202, USA

    David Lominadze

Authors
  1. Nino Muradashvili
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard L. Benton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathryn E. Saatman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suresh C. Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Lominadze
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Lominadze.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muradashvili, N., Benton, R.L., Saatman, K.E. et al. Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice. Metab Brain Dis 30, 411–426 (2015). https://doi.org/10.1007/s11011-014-9550-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9550-3

Keywords

Search

Navigation