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Cited by 205Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNanoparticle-Based Drug Delivery

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery

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Vazana, U., Veksler, R., Pell, G. S., Prager, O., Fassler, M., Chassidim, Y., Roth, Y., Shahar, H. +11 more·2016·Journal of Neuroscience
DOI 10.1523/jneurosci.0587-16.2016PMC PMC4951577
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Abstract

UNLABELLED: The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders.

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  • Astrocyte reactivity has frequently been associated with neuroinflammation, unfavorable glial scar formation, glutamate dyshomeostasis, altered coverage of synapses and blood vessels, and BBB breakout.

    “Hence, astrocyte reactivity has frequently been associated with neuroinflammation, unfavorable glial scar formation [7, 8, 9, 37, 38, 43, 48, 49], glutamate dyshomeostasis [43, 50, 51], altered coverage of synapses and blood vessels, and BBB breakout [38, 42, 43, 45, 46, 47].”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [51]

    The Discussion (page not available in our copy) says increased BBB permeability can induce an astrocytic transformation associated with neuroinflammation and impaired control of the extracellular milieu. That supports an association involving astrocyte reactivity and BBB dysfunction, but the paper does not establish the cited sentence’s additional claims about glial scarring or altered coverage of synapses and blood vessels, nor does it directly link astrocyte reactivity to glutamate dyshomeostasis. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Both proinflammatory molecules and glutamate have been broadly shown to impair the structure and function of brain endothelium.

    “Both proinflammatory molecules and glutamate have been broadly shown to impair the structure and function of brain endothelium [50, 51].”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [51]

    The section “Excessive glutamate release enhances vascular permeability” reports that glutamate increased brain-vessel permeability and describes earlier findings of altered endothelial tight-junction proteins. The cited paper does not show that proinflammatory molecules impair brain endothelium; its Discussion instead describes neuroinflammation as associated with increased endothelial permeability. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Glutamate dyshomeostasis is associated with vascular deterioration and BBB breakdown.

    “In fact, astroglial reactivity [1], astrocyte‐mediated inflammation [50], and glutamate dyshomeostasis [51] are associated with vascular deterioration and BBB breakdown.”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [51]

  • Hyperactivated astrocytes and microglia support excitotoxicity through the exacerbated release of glutamate in response to Aβ, and GABA‐producing astrocytes are commonly found in AD.

    “hyperactivated astrocytes and microglia, support excitotoxicity through the exacerbated release of glutamate in response to Aβ [37, 38, 40, 43, 50, 51, 117, 118], and even GABA‐producing astrocytes are commonly found in AD [42, 97, 119].”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [51]

    The Introduction and 'Excessive glutamate release enhances vascular permeability' section discuss glutamate released with neuronal activation and its effects on the blood–brain barrier. Our copy does not address Aβ-induced glutamate release by astrocytes or microglia, or the prevalence of GABA-producing astrocytes in Alzheimer’s disease. Searches for those terms found no supporting passage; page numbers were not supplied. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 63

  1. 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 · DOI
  2. Andra ´s 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 endothe- lial cells. J Cereb Blood Flow Metab 27:1431-1443. CrossRef Medline · DOI
  3. Baker GJ, Yadav VN, Motsch S, Koschmann C, Calinescu AA MY, Camelo- Piragua SI, Orringer D, Bannykh S, Nichols WS, deCarvalho AC, Mik- kelsen 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 · DOI
  4. Bankstahl JP, Hoffmann K, Bethmann K, Lo ¨scher W (2008) Glutamate is critically involved in seizure-induced overexpression of P-glycoprotein in the brain. Neuropharmacology 54:1006 -1016. CrossRef Medline · DOI
  5. Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocam- pus during transient cerebral ischemia monitored by intracerebral micro- dialysis. J Neurochem 43:1369 -1374. CrossRef Medline · DOI
  6. Bradford HF (1995) Glutamate, GABA and epilepsy. Prog Neurobiol 47: 477-511. CrossRef Medline · DOI
  7. Brown RC, Davis TP (2002) Calcium modulation of adherens and tight junction function: a potential mechanism for blood-brain barrier disrup- tion after stroke. Stroke 33:1706 -1711. CrossRef Medline · DOI
  8. Cacheaux LP, Ivens S, David Y, Lakhter AJ, Bar-Klein GS, Shapira M, Heine- mann U, Friedman A, Kaufer D (2009) Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci 29:8927- 8935. CrossRef Medline · DOI
  9. Carmignoto G, Go ´mez-Gonzalo M (2010) The contribution of astrocyte signalling to neurovascular coupling. Brain Res Rev 63:138 -148. CrossRef Medline · DOI
  10. 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 · DOI
  11. Chassidim Y, Vazana U, Prager O, Veksler R, Bar-Klein G, Schoknecht K, Fassler M, Lublinsky S, Shelef I (2015) Analyzing the blood-brain bar- rier: The benefits of medical imaging in research and clinical practice. Semin Cell Dev Biol 38:43-52. CrossRef Medline · DOI
  12. David Y, Cacheaux LP, Ivens S, Lapilover E, Heinemann UK, Kaufer D, Friedman A (2009) Astrocytic dysfunction in epileptogenesis: conse- quence of altered potassium and glutamate homeostasis? J Neurosci 29: 10588 -10599. CrossRef Medline · DOI
  13. Davies DC (2002) Blood-brain barrier breakdown in septic encephalopa- thy and brain tumours. J Anat 200:639 -646. CrossRef Medline · DOI
  14. 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 · DOI
  15. 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 · DOI
  16. Fariello RG (1976) Parenteral penicillin in rats: an experimental model of multifocal epilepsy. Epilepsia 17:217-222. CrossRef Medline · DOI
  17. 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 · DOI
  18. Fishman RA (1966) Blood-brain and csf barriers to penicillin and related organic acids. Arch Neurol 15:113-124. CrossRef Medline · DOI
  19. Friedman A (2011) Blood-brain barrier dysfunction, status epilepticus, sei- zures, and epilepsy: a puzzle of a chicken and egg? Epilepsia 52:19 -20. CrossRef Medline · DOI
  20. 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 · DOI
  21. Gersner R, Kravetz E, Feil J, Pell G, Zangen A (2011) Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplastic- ity: differential outcomes in anesthetized and awake animals. J Neurosci 31:7521-7526. CrossRef Medline · DOI · Paper page
  22. 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 · DOI
  23. Huang CY, Wang LC, Wang HK, Pan CH, Cheng YY, Shan YS, Chio CC, Tsai KJ (2015) Memantine alleviates brain injury and neurobehavioral defi- cits after experimental subarachnoid hemorrhage. Mol Neurobiol 51: 1038 -1052. CrossRef Medline · DOI
  24. 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 · DOI
  25. 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 · DOI
  26. Krizbai IA, Deli MA, Pestena ´cz A, Siklo ´s L, Szabo ´CA, Andra ´s I, Joo ´F (1998) Expression of glutamate receptors on cultured cerebral endothelial cells. J Neurosci Res 54:814 -819. CrossRef Medline · DOI
  27. Librizzi L, Noe `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 · DOI · Paper page
  28. Mecocci P, Parnetti L, Reboldi GP, Santucci C, Gaiti A, Ferri CG, I, Romag- noli 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 · DOI
  29. Miguel-Hidalgo JJ, Alvarez XA, Cacabelos R, Quack G (2002) Neuroprotec- tion by memantine against neurodegeneration induced by beta-amy- loid(1-40). Brain Res 958:210 -221. CrossRef Medline · DOI
  30. 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 · DOI
  31. Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LF (1999) Failure of the competitive N-methyl-D-aspartate antagonist Sel- fotel (CGS 19755) in the treatment of severe head injury: results of two Phase III clinical trials. J Neurosurg 91:737-743. CrossRef Medline · DOI
  32. 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 · DOI
  33. 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 · DOI
  34. Nishizawa Y (2001) Glutamate release and neuronal damage in ischemia. Life Sci 69:369 -381. CrossRef Medline · DOI
  35. Nitsch C, Hubauer H (1986) Distant blood-brain barrier opening in sub- fields of the rat hippocampus after intrastriatal injections of kainic acid but not ibotenic acid. Neurosci Lett 64:53-58. CrossRef Medline · DOI
  36. 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 · DOI
  37. Prager O, Chassidim Y, Klein C, Levi H, Shelef I, Friedman A (2010) Dy- namic in vivo imaging of cerebral blood flow and blood-brain barrier permeability. Neuroimage 49:337-344. CrossRef Medline · DOI
  38. Rao VL, Dogan A, Todd KG, Bowen KK, Dempsey RJ (2001) Neuroprotec- tion by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res 911:96 -100. CrossRef Medline · DOI
  39. Raychaudhuri B, Han Y, Lu T, Vogelbaum MA (2007) Aberrant constitutive activation of nuclear factor B in glioblastoma multiforme drives invasive phenotype. J Neurooncol 85:39 -47. CrossRef Medline · DOI
  40. Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic- ischemic brain damage. Ann Neurol 19:105-111. CrossRef Medline · DOI
  41. Schoknecht K, Prager O, Vazana U, Kamintsky L, Harhausen D, Zille M, Figge L, Chassidim Y, Schellenberger E, Kova ´cs R, Heinemann U, Friedman A (2014) Monitoring stroke progression: in vivo imaging of cortical perfu- sion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model. J Cereb Blood Flow Metab 34:1791-1801. CrossRef Medline · DOI
  42. Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Fried- man A (2004) Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 24:7829 -7836. CrossRef Medline · DOI
  43. 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 ac- tivation of NMDA receptor. Am J Physiol Hear Circ Physiol 285:H2592- H2598. CrossRef Medline · DOI
  44. Sharp CD, Houghton J, Elrod JW, Warren A, Jackson IV TH, Jawahar A, Nanda A, Minagar A, Alexander JS, Christopher D (2005) N-methyl-D- aspartate receptor activation in human cerebral endothelium promotes intracellular oxidant stress. Am J Physiol Hear Circ Physiol 3932: 1893-1899. CrossRef Medline · DOI
  45. Sontheimer H (2008) A role for glutamate in growth and invasion of pri- mary brain tumors. J Neurochem 105:287-295. CrossRef Medline · DOI
  46. 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 · DOI
  47. Tofts PS (1997) Modeling tracer kinetics in dynamic Gd-DTPA MR imag- ing. J Magn Reson Imaging 7:91-101. CrossRef Medline · DOI
  48. Tomkins O, Shelef I, Kaizerman I, Eliushin A, Afawi Z, Misk A, Gidon M, Cohen A, Zumsteg D, Friedman A (2008) Blood-brain barrier disrup- tion in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry 79:774 - 777. CrossRef Medline · DOI
  49. 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 · DOI
  50. 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 · DOI
  51. van Vliet EA, da Costa Arau ´jo 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 · DOI · Paper page
  52. Van Vliet EA, Otte WM, Gorter JA, RM Dijkhuizen RM, Wadman WJ (2014) Longitudinal assessment of blood-brain barrier leakage during epilepto- genesis in rats. A quantitative MRI study. Neurobiol Dis 63:74 -84. CrossRef Medline · DOI
  53. Veksler R, Shelef I, Friedman A (2014) Blood-brain barrier imaging in hu- man neuropathologies. Arch Med Res 45:646 -652. CrossRef Medline · DOI
  54. Watson BD, Dietrich WD, Prado R, Ginsberg MD (1987) Argon laser- induced arterial photothrombosis characterization and possible applica- tion to therapy of arteriovenous malformations. J Neurosurg 66:748 -754. CrossRef Medline · DOI
  55. 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 · DOI
  56. 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 · DOI
  57. 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 ex- citatory synaptogenesis through astrocytic TGF-␤/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction. Neurobiol Dis 78:115-125. CrossRef Medline · DOI
  58. 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 · DOI
  59. 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 · DOI
  60. Yoon KW, Covey DF, Rothman SM (1993) Multiple mechanisms of picro- toxin block of GABA-induced currents in rat hippocampal neurons. J Physiol 464:423-439. CrossRef Medline · DOI
  61. 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 · DOI
  62. Zangen A, Hyodo K (2002) Transcranial magnetic stimulation induces in- creases in extracellular levels of dopamine and glutamate in the nucleus accumbens. Neuroreport 13:2401-2405. CrossRef Medline · DOI · Paper page
  63. Zangen A, Roth Y, Voller B, Hallett M (2005) Transcranial magnetic stim- ulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol 116:775-779. CrossRef Medline · DOI

Cited by

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Authors
Vazana, U., Veksler, R., Pell, G. S., Prager, O., Fassler, M., Chassidim, Y., Roth, Y., Shahar, H., Zangen, A., Raccah, R., Onesti, E., Ceccanti, M., Colonnese, C., Santoro, A., Salvati, M., D'Elia, A., Nucciarelli, V., Inghilleri, M., & Friedman, A.
Affiliations
  • Ben-Gurion University of the Negev (IL)
  • BrainsWay (Israel) (IL)
  • Sapienza University of Rome (IT)
  • Dalhousie University (CA)
ORCID
Venue
Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2016-07-20
Volume
36
Issue
29
Pages
7727-7739
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.0587-16.2016
PMC
PMC4951577
OpenAlex
W2483981362
Cited by
205
References
4
Citations by year
2026: 18 · 2025: 25 · 2024: 27 · 2023: 21 · 2022: 26 · 2021: 21 · 2020: 25 · 2019: 16 · 2018: 12 · 2017: 11 · 2016: 3
FWCI
6.62
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
Funders
  • BrainsWay
  • Nova Scotia Health Research Foundation
  • European Commission (2007–2013, FP7 2007-2013, FP7/2007, 602102)
  • Israel Science Foundation (FP7/2007-2013)
  • National Institutes of Health (FP7/2007-2013, RO1/NINDS NS066005)
  • National Institute of Neurological Disorders and Stroke (R56NS066005, 602102, RO1/NINDS NS066005, R01NS066005)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
blood-brain barrier permeability, glutamate, NMDA receptor, recurrent seizures, cerebral cortex, vascular permeability, transcranial magnetic stimulation, NMDA receptor antagonists, high-grade glioma, brain tumor drug delivery, neuroprotection, contrast-enhanced MRI, intravital microscopy
MeSH terms
Adult, Aged, Animals, Blood-Brain Barrier, Brain Neoplasms, Disease Models, Animal, Double-Blind Method, Female, Glioblastoma, Humans, Male, Middle Aged, Permeability, Seizures, 4-Aminopyridine, Treatment Outcome, Rats, Sprague-Dawley, Neuroprotective Agents, Glutamic Acid, Stroke, Potassium Channel Blockers, Rats

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