Glutamate-mediated blood–brain barrier opening: Implications for neuroprotection and drug delivery

Journal of Neuroscience

Volumn 36, Issue 29, 2016, Pages 7727-7739

  Vazana, Udi ^a   Veksler, Ronel ^a   Pell, Gaby S ^a,b   Prager, Ofer ^a   Fassler, Michael ^a   Chassidim, Yoash ^a   Roth, Yiftach ^b   Shahar, Hamutal ^a,b   Zangen, Abraham ^a   Raccah, Ruggero ^c   Onesti, Emanuela ^d   Ceccanti, Marco ^d   Colonnese, Claudio ^e   Santoro, Antonio ^e   Salvati, Maurizio ^e   D’Elia, Alessandro ^e   Nucciarelli, Valter ^e   Inghilleri, Maurizio ^d   Friedman, Alon ^a,f  

^a BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^b Brainsway Ltd   (Israel)

^c Atid   (Italy)

^d SAPIENZA UNIVERSITY OF ROME   (Italy)

^e SAPIENZA UNIVERSITY OF ROME   (Italy)

^f DALHOUSIE UNIVERSITY   (Canada)

Author keywords

Blood brain barrier; Glutamate; Imaging; N methyl D aspartate; Transcranial magnetic stimulation

Indexed keywords

CALCIUM ION; GLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NITRIC OXIDE; OXYGEN; PENICILLIN G SODIUM; TEMOZOLOMIDE; FAMPRIDINE; NEUROPROTECTIVE AGENT; POTASSIUM CHANNEL BLOCKING AGENT;

ADJUVANT THERAPY; ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; BLOOD VESSEL DIAMETER; BLOOD VESSEL PERMEABILITY; BRAIN BLOOD FLOW; CLINICAL ARTICLE; CONFOCAL LASER MICROSCOPY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DELIVERY SYSTEM; ELECTROCORTICOGRAPHY; EXPERIMENTAL SEIZURE; FEMALE; FLUORESCENCE ANGIOGRAPHY; FLUORESCENCE IMAGING; GLIOBLASTOMA; HUMAN; INTRAVITAL MICROSCOPY; MALE; MIDDLE AGED; NERVE STIMULATION; NEUROMODULATION; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RAT; THROMBOSIS; TRANSCRANIAL MAGNETIC STIMULATION; ANIMAL; BRAIN TUMOR; CEREBROVASCULAR ACCIDENT; CHEMICALLY INDUCED; COMPLICATION; DIAGNOSTIC IMAGING; DISEASE MODEL; DRUG EFFECTS; PERMEABILITY; SEIZURE; SPRAGUE DAWLEY RAT; TREATMENT OUTCOME;

4-AMINOPYRIDINE; ADULT; AGED; ANIMALS; BLOOD-BRAIN BARRIER; BRAIN NEOPLASMS; DISEASE MODELS, ANIMAL; DOUBLE-BLIND METHOD; FEMALE; GLIOBLASTOMA; GLUTAMIC ACID; HUMANS; MALE; MIDDLE AGED; NEUROPROTECTIVE AGENTS; PERMEABILITY; POTASSIUM CHANNEL BLOCKERS; RATS; RATS, SPRAGUE-DAWLEY; SEIZURES; STROKE; TREATMENT OUTCOME;

EID: 84978708663     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0587-16.2016     Document Type: Article

References (70)

1. Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7:41–53. CrossRef Medline
2. Aitken PG, Jing J, Young J, Somjen GG (1991) Ion channel involvement in hypoxia-induced spreading depression in hippocampal slices. Brain Res 541:7–11. CrossRef Medline
3. András IE, Deli MA, Veszelka S, Hayashi K, Hennig B, Toborek M (2007) The NMDA and AMPA/KA receptors are involved in glutamate-induced alterations of occludin expression and phosphorylation in brain endothelial cells. J Cereb Blood Flow Metab 27:1431–1443. CrossRef Medline
4. Baker GJ, Yadav VN, Motsch S, Koschmann C, Calinescu AA MY, Camelo- Piragua SI, Orringer D, Bannykh S, Nichols WS, deCarvalho AC, Mikkelsen T, Castro MG, Lowenstein PR (2014) Mechanisms of glioma formation: iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy. Neoplasia 16:543–561. CrossRef Medline
5. Bankstahl JP, Hoffmann K, Bethmann K, Löscher W (2008) Glutamate is critically involved in seizure-induced overexpression of P-glycoprotein in the brain. Neuropharmacology 54:1006–1016. CrossRef Medline
6. Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1374. CrossRef Medline
7. Bradford HF (1995) Glutamate, GABA and epilepsy. Prog Neurobiol 47: 477–511. CrossRef Medline
8. Brown RC, Davis TP (2002) Calcium modulation of adherens and tight junction function: a potential mechanism for blood–brain barrier disruption after stroke. Stroke 33:1706–1711. CrossRef Medline
9. Cacheaux LP, Ivens S, David Y, Lakhter AJ, Bar-Klein GS, Shapira M, Heinemann U, Friedman A, Kaufer D (2009) Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci 29:8927–8935. CrossRef Medline
10. Carmignoto G, Gómez-Gonzalo M (2010) The contribution of astrocyte signalling to neurovascular coupling. Brain Res Rev 63:138–148. CrossRef Medline
11. Chassidim Y, Veksler R, Lublinsky S, Pell GS, Friedman A, Shelef I (2013) Quantitative imaging assessment of blood–brain barrier permeability in humans. Fluids Barriers CNS 10:9. CrossRef Medline
12. Chassidim Y, Vazana U, Prager O, Veksler R, Bar-Klein G, Schoknecht K, Fassler M, Lublinsky S, Shelef I (2015) Analyzing the blood–brain barrier: The benefits of medical imaging in research and clinical practice. Semin Cell Dev Biol 38:43–52. CrossRef Medline
13. David Y, Cacheaux LP, Ivens S, Lapilover E, Heinemann UK, Kaufer D, Friedman A (2009) Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? J Neurosci 29: 10588–10599. CrossRef Medline
14. Davies DC (2002) Blood–brain barrier breakdown in septic encephalopathy and brain tumours. J Anat 200:639–646. CrossRef Medline
15. De Bock M, Wang N, Decrock E, Bol M, Gadicherla AK, Culot M, Cecchelli R, Bultynck G, Leybaert L (2013) Endothelial calcium dynamics, connexin channels and blood–brain barrier function. Prog Neurobiol 108:1–20. CrossRef Medline
16. Elger CE, Speckmann EJ (1983) Experimental Section: Penicillin-induced epileptic foci in the motor cortex: vertical inhibition. Electroencephalogr Clin Neurophysiol 56:604–622. CrossRef Medline
17. Fariello RG (1976) Parenteral penicillin in rats: an experimental model of multifocal epilepsy. Epilepsia 17:217–222. CrossRef Medline
18. Fink J, Born D, Chamberlain MC (2012) Radiation necrosis: relevance with respect to treatment of primary and secondary brain tumors. Curr Neurol Neurosci Rep 12:276–285. CrossRef Medline
19. Fishman RA (1966) Blood–brain and csf barriers to penicillin and related organic acids. Arch Neurol 15:113–124. CrossRef Medline
20. Friedman A (2011) Blood–brain barrier dysfunction, status epilepticus, seizures, and epilepsy: a puzzle of a chicken and egg? Epilepsia 52:19–20. CrossRef Medline
21. Friedman A, Bar-Klein G, Serlin Y, Parmet Y, Heinemann U, Kaufer D (2014) Should losartan be administered following brain injury? Expert Rev Neurother 14:1365–1375. CrossRef Medline
22. Gersner R, Kravetz E, Feil J, Pell G, Zangen A (2011) Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity: differential outcomes in anesthetized and awake animals. J Neurosci 31:7521–7526. CrossRef Medline
23. Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, Wang X, Rosenberg GA, Lo EH, Moskowitz MA (2004) Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 113:1447–1455. CrossRef Medline
24. Huang CY, Wang LC, Wang HK, Pan CH, Cheng YY, Shan YS, Chio CC, Tsai KJ (2015) Memantine alleviates brain injury and neurobehavioral deficits after experimental subarachnoid hemorrhage. Mol Neurobiol 51: 1038–1052. CrossRef Medline
25. Ikonomidou C, Turski L (2002) Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 1:383–386. CrossRef Medline
26. Jander S, Schroeter M, Stoll G (2000) Role of NMDA receptor signaling in the regulation of inflammatory gene expression after focal brain ischemia. J Neuroimmunol 109:181–187. CrossRef Medline
27. Krizbai IA, Deli MA, Pestenácz A, Siklós L, Szabó CA, András I, Joó F (1998) Expression of glutamate receptors on cultured cerebral endothelial cells. J Neurosci Res 54:814–819. CrossRef Medline
28. Librizzi L, Noè F, Vezzani A, de Curtis M, Ravizza T (2012) Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage. Ann Neurol 72:82–90. CrossRef Medline
29. Mecocci P, Parnetti L, Reboldi GP, Santucci C, Gaiti A, Ferri CG, I, Romagnoli M, Cadini D, Senin U (1991) Blood–brain-barrier in a geriatric population: barrier function in degenerative and vascular dementias. Acta Neurol Scand 84:210–213. CrossRef Medline
30. Miguel-Hidalgo JJ, Alvarez XA, Cacabelos R, Quack G (2002) Neuroprotection by memantine against neurodegeneration induced by beta-amyloid(1–40). Brain Res 958:210–221. CrossRef Medline
31. Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, Toga AW, Jacobs RE, Liu CY, Amezcua L, Harrington MG, Chui HC, Law M, Zlokovic BV (2015) Blood–brain barrier breakdown in the aging human hippocampus. Neuron 85:296–302. CrossRef Medline
32. Mooradian AD (1997) Central nervous system complications of diabetes mellitus–a perspective from the blood–brain barrier. Brain Res Rev 23: 210–218. CrossRef Medline
33. Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LF (1999) Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two Phase III clinical trials. J Neurosurg 91:737–743. CrossRef Medline
34. Morris RG (1989) Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. J Neurosci 9:3040–3057. Medline
35. Mottaghy FM, Gangitano M, Horkan C, Chen Y, Pascual-Leone A, Schlaug G (2003) Repetitive TMS temporarily alters brain diffusion. Neurology 60: 1539–1541. CrossRef Medline
36. Narahashi T, Moore JW, Scott WR (1964) Tetrodotoxin blockage of sodium conductance increase in lobster giant axons. J Gen Physiol 47:965–974. CrossRef Medline
37. Nishizawa Y (2001) Glutamate release and neuronal damage in ischemia. Life Sci 69:369–381. CrossRef Medline
38. Nitsch C, Hubauer H (1986) Distant blood–brain barrier opening in subfields of the rat hippocampus after intrastriatal injections of kainic acid but not ibotenic acid. Neurosci Lett 64:53–58. CrossRef Medline
39. Parfenova H, Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan RF, Leffler CW (2006) Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am J Physiol Cell Physiol 290:C1399–C1410. CrossRef Medline
40. Phurrough S, Jacques L, Turner T, Rollins J (2007) Decision memo for blood brain barrier disruption (BBBD) chemotherapy (CAG-00333N). Baltimore: Centers for Medicaid and Medicare Services.
41. Prager O, Chassidim Y, Klein C, Levi H, Shelef I, Friedman A (2010) Dynamic in vivo imaging of cerebral blood flow and blood–brain barrier permeability. Neuroimage 49:337–344. CrossRef Medline
42. Rao VL, Dogan A, Todd KG, Bowen KK, Dempsey RJ (2001) Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res 911:96–100. CrossRef Medline
43. Raychaudhuri B, Han Y, Lu T, Vogelbaum MA (2007) Aberrant constitutive activation of nuclear factor κB in glioblastoma multiforme drives invasive phenotype. J Neurooncol 85:39–47. CrossRef Medline
44. Rossi S, Hallett M, Rossini PM, Pascual-Leone A (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120:2008–2039. CrossRef Medline
45. Roth Y, Padberg F, Zangen A (2007) Transcranial magnetic stimulation of deep brain regions: principles and methods. Transcranial Brain Stimul Treat Psychiatr Disord 23:204–224.
46. Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic–ischemic brain damage. Ann Neurol 19:105–111. CrossRef Medline
47. Schoknecht K, Prager O, Vazana U, Kamintsky L, Harhausen D, Zille M, Figge L, Chassidim Y, Schellenberger E, Kovács R, Heinemann U, Friedman A (2014) Monitoring stroke progression: in vivo imaging of cortical perfusion, blood–brain barrier permeability and cellular damage in the rat photothrombosis model. J Cereb Blood Flow Metab 34:1791–1801. CrossRef Medline
48. Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Friedman A (2004) Lasting blood–brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 24:7829–7836. CrossRef Medline
49. Sharp CD, Hines I, Houghton J, Warren A, Jackson IV TH, Jawahar A, Nanda A, Elrod JW, Long A, Chi A, Minagar A, Alexander JS (2003) Glutamate causes a loss in human cerebral endothelial barrier integrity through activation of NMDA receptor. Am J Physiol Hear Circ Physiol 285:H2592–H2598. CrossRef Medline
50. Sharp CD, Houghton J, Elrod JW, Warren A, Jackson TH.,IV, Jawahar A, Nanda A, Minagar A, Alexander JS, Christopher D (2005) N-methyl-Daspartate receptor activation in human cerebral endothelium promotes intracellular oxidant stress. Am J Physiol Hear Circ Physiol 3932: 1893–1899. CrossRef Medline
51. Sontheimer H (2008) A role for glutamate in growth and invasion of primary brain tumors. J Neurochem 105:287–295. CrossRef Medline
52. Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci U S A 100: 7319–7324. CrossRef Medline
53. Tofts PS (1997) Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging 7:91–101. CrossRef Medline
54. Tomkins O, Shelef I, Kaizerman I, Eliushin A, Afawi Z, Misk A, Gidon M, Cohen A, Zumsteg D, Friedman A (2008) Blood–brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry 79:774–777. CrossRef Medline
55. Uva L, Trombin F, Carriero G, Avoli M, de Curtis M (2013) Seizure-like discharges induced by 4-aminopyridine in the olfactory system of the in vitro isolated guinea pig brain. Epilepsia 54:605–615. CrossRef Medline
56. van Breemen MS, Wilms EB, Vecht CJ (2007) Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 6:421–430. CrossRef Medline
57. van Vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter JA (2007) Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130:521–534. CrossRef Medline
58. Van Vliet EA, Otte WM, Gorter JA, RM Dijkhuizen RM, Wadman WJ (2014) Longitudinal assessment of blood–brain barrier leakage during epileptogenesis in rats. A quantitative MRI study. Neurobiol Dis 63:74–84. CrossRef Medline
59. Veksler R, Shelef I, Friedman A (2014) Blood–brain barrier imaging in human neuropathologies. Arch Med Res 45:646–652. CrossRef Medline
60. Watson BD, Dietrich WD, Prado R, Ginsberg MD (1987) Argon laserinduced arterial photothrombosis characterization and possible application to therapy of arteriovenous malformations. J Neurosurg 66:748–754. CrossRef Medline
61. Weber TG, Osl F, Renner A, Poschinger T, Galban S, Rehemtulla A, Scheuer W (2014) Apoptosis imaging for monitoring DR5 antibody accumulation and pharmacodynamics in brain tumors noninvasively. Cancer Res 74: 1913–1923. CrossRef Medline
62. Weissberg I, Veksler R, Kamintsky L, Saar-Ashkenazy R, Milikovsky DZ, Shelef I, Friedman A (2014) Imaging blood–brain barrier dysfunction in American football players. JAMA Neurol 71:1453–1455. CrossRef Medline
63. Weissberg I, Wood L, Kamintsky L, Vazquez O, Milikovsky DZ, Alexander A, Oppenheim H, Ardizzone C, Becker A, Frigerio F, Vezzani A, Buckwalter MS, Huguenard J, Friedman A, Kaufer D (2015) Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood–brain barrier dysfunction. Neurobiol Dis 78:115–125. CrossRef Medline
64. Wolman M, Klatzo I, Chui E, Wilmes F, Nishimoto K, Fujiwara K, Spatz M (1981) Evaluation of the dye-protein tracers in pathophysiology of the blood–brain barrier. Acta Neuropathol 54:55–61. CrossRef Medline
65. Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW (2005) ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow. Blood 106: 584–592. CrossRef Medline
66. Yoon KW, Covey DF, Rothman SM (1993) Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons. J Physiol 464:423–439. CrossRef Medline
67. Yoshiyama M, Roppolo JR, de Groat WC (1995) Effects of GYKI 52466 and CNQX, AMPA/kainate receptor antagonists, on the micturition reflex in the rat. Brain Res 691:185–194. CrossRef Medline
68. Zangen A, Hyodo K (2002) Transcranial magnetic stimulation induces increases in extracellular levels of dopamine and glutamate in the nucleus accumbens. Neuroreport 13:2401–2405. CrossRef Medline
69. Zangen A, Roth Y, Voller B, Hallett M (2005) Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol 116:775–779. CrossRef Medline
70. Zlokovic BV (2008) The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201. CrossRef Medline