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Article ; Online: Biochemical opening of the blood-brain barrier.

Black, Keith L

2022 Volume 15, Issue 1-3, Page(s) 37–52

Abstract: Biochemical agents that can influence the abnormal BBB are reviewed. Vasoactive compounds, including leukotrienes, bradykinin, histamine appear to selectively increase permeability in abnormal brain capillaries. Normal brain capillaries resist the ... ...

Abstract	Biochemical agents that can influence the abnormal BBB are reviewed. Vasoactive compounds, including leukotrienes, bradykinin, histamine appear to selectively increase permeability in abnormal brain capillaries. Normal brain capillaries resist the effects of these compounds through an 'enzymatic barrier' that may inactivate vasoactive agents. In contrast, this enzymatic barrier is lost in certain diseased states, allowing vasoactive compounds to selectively increase permeability in abnormal capillaries. Clinically, intracarotid infusion of leukotrienes, bradykinin and other vasoactive agents can increase drug delivery to diseased tissue.
Language	English
Publishing date	2022-02-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
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Article ; Online: Activated T cell therapy targeting glioblastoma cancer stem cells.

Miyaguchi, Ken / Wang, Hongqiang / Black, Keith L / Shiao, Stephen L / Wang, Rongfu / Yu, John S

Scientific reports

2023 Volume 13, Issue 1, Page(s) 196

Abstract: Naïve T cells become effector T cells following stimulation by antigen-loaded dendritic cells (DCs) and sequential cytokine activation. We aimed to develop procedures to efficiently activate T cells with tumor-associated antigens (TAAs) to glioblastoma ( ... ...

Abstract	Naïve T cells become effector T cells following stimulation by antigen-loaded dendritic cells (DCs) and sequential cytokine activation. We aimed to develop procedures to efficiently activate T cells with tumor-associated antigens (TAAs) to glioblastoma (GBM) stem cells. To remove antigen presentation outside of the immunosuppressive tumor milieu, three different glioma stem cell (GSC) specific antigen sources to load DCs were compared in their ability to stimulate lymphocytes. An activated T cell (ATC) protocol including cytokine activation and expansion in culture to target GSCs was generated and optimized for a planned phase I clinical trial. We compared three different antigen-loading methods on DCs to effectively activate T cells, which were GBM patient-derived GSC-lysate, acid-eluate of GSCs and synthetic peptides derived from proteins expressed in GSCs. DCs derived from HLA-A2 positive blood sample were loaded with TAAs. Autologous T cells were activated by co-culturing with loaded DCs. Efficiency and cytotoxicity of ATCs were evaluated by targeting TAA-pulsed DCs or T2 cells, GSCs, or autologous PHA-blasts. Characteristics of ATCs were evaluated by Flow Cytometry and ELISpot assay, which showed increased number of ATCs secreting IFN-γ targeting GSCs as compared with non-activated T cells and unloaded target cells. Neither GSC-lysate nor acid-eluate loading showed enhancement in response of ATCs but the synthetic peptide pool showed significantly increased IFN-γ secretion and increased cytotoxicity towards target cells. These results demonstrate that ATCs activated using a TAA synthetic peptide pool efficiently enhance cytotoxicity specifically to target cells including GSC.
MeSH term(s)	Humans ; T-Lymphocytes, Cytotoxic ; Glioblastoma/therapy ; Glioblastoma/metabolism ; Interferon-gamma/metabolism ; Antigens, Neoplasm ; Peptides/metabolism ; Neoplastic Stem Cells/metabolism ; Cell- and Tissue-Based Therapy ; Dendritic Cells
Chemical Substances	Interferon-gamma (82115-62-6) ; Antigens, Neoplasm ; Peptides
Language	English
Publishing date	2023-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-27184-w
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Article ; Online: Glatiramer Acetate Immunomodulation: Evidence of Neuroprotection and Cognitive Preservation.

Kasindi, Arielle / Fuchs, Dieu-Trang / Koronyo, Yosef / Rentsendorj, Altan / Black, Keith L / Koronyo-Hamaoui, Maya

Cells

2022 Volume 11, Issue 9

Abstract: Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment ... ...

Abstract	Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients. Furthermore, results from these and animal studies suggest that GA has a direct immunomodulatory effect on adaptive and innate immune cell phenotypes and responses. These MOAs have been postulated to have a common neuroprotective impact in several neuroinflammatory and neurodegenerative diseases. Notably, several clinical studies report that the use of GA mitigated MS-associated cognitive decline. Its propensity to ameliorate neuro-proinflammatory and degenerative processes ignites increased interest in potential alternate uses such as in age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). Preclinical studies are exploring less frequent subcutaneous administration of GA, such as once weekly or monthly or a single dosing regimen. Indeed, cognitive functions were found to be either preserved, reversed, or improved after the less frequent treatment regimens with GA in animal models of AD. In this systematic review, we examine the potential novel uses of GA across clinical and pre-clinical studies, with evidence for its beneficial impact on cognition. Future investigation in large-size, double-blind clinical trials is warranted to establish the impact of GA immunomodulation on neuroprotection and cognitive preservation in various neurological conditions.
MeSH term(s)	Animals ; Cognition ; Encephalomyelitis, Autoimmune, Experimental ; Glatiramer Acetate/pharmacology ; Glatiramer Acetate/therapeutic use ; Humans ; Immunomodulation ; Neuroprotection ; Randomized Controlled Trials as Topic
Chemical Substances	Glatiramer Acetate (5M691HL4BO)
Language	English
Publishing date	2022-05-07
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11091578
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Meningioma transformation to glioblastoma following stereotactic radiosurgery: A case report and review of the literature.

Boyke, Andre Everett / Michel, Michelot / Garcia, Catherine Michelle / Bannykh, Serguei I / Chan, Julie Lynn / Black, Keith L

Surgical neurology international

2023 Volume 14, Page(s) 364

Abstract: Background: Meningiomas are the most common primary intracranial tumor with increasing incidence. Stereotactic Radiosurgery Gamma Knife (SRS-GK) is a commonly used modality for neoadjuvant and adjuvant treatment of these tumors and is often necessary ... ...

Abstract	Background: Meningiomas are the most common primary intracranial tumor with increasing incidence. Stereotactic Radiosurgery Gamma Knife (SRS-GK) is a commonly used modality for neoadjuvant and adjuvant treatment of these tumors and is often necessary for long-term disease control, particularly for the World Health Organization grade II/III meningiomas. While there is strong evidence to support the use of SRS-GK for meningioma, there exists a risk of secondary malignancy that is not well understood. We report a case of glioblastoma (GBM) that arose near the bed of a meningioma previously treated with SRS-GK and discuss other cases of GBM that emerged at a site of meningioma reported in the literature. Case description: A 79-year-old female with a history of a blood-clotting disorder presented to the hospital with sudden facial sensory disturbances. On magnetic resonance imaging (MRI), a homogeneously enhancing lesion was observed in the right temporal lobe, consistent with a meningioma. Following 2 years of surveillance, the patient underwent SRS-GK for enlargement of the lesion. The patient later presented with headache and gait instability 12 years following SRS-GK. MRI revealed a large ring-enhancing lesion with surrounding edema histologically confirmed to be a GBM. At 9 months following initial tumor resection and a combination of radiotherapy and temozolomide, the patient was neurologically intact. Conclusion: There is a very small risk of meningioma to GBM conversion following SRS. Although SRS-GK poses a risk of secondary malignancy, there are some reported cases that underwent malignant transformation without SRS-GK. This suggests that SRS-GK is not the only factor in transformation and is a reasonable therapeutic modality to consider utilizing. Patients and their families should be appropriately counseled on the potential risks of radiation therapy, even for benign lesions like a meningioma.
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Case Reports
ISSN	2229-5097
ISSN	2229-5097
DOI	10.25259/SNI_599_2023
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Article: Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance.

Dumitrascu, Oana M / Doustar, Jonah / Fuchs, Dieu-Trang / Koronyo, Yosef / Sherman, Dale S / Miller, Michelle Shizu / Johnson, Kenneth O / Carare, Roxana O / Verdooner, Steven R / Lyden, Patrick D / Schneider, Julie A / Black, Keith L / Koronyo-Hamaoui, Maya

bioRxiv : the preprint server for biology

2024

Abstract: Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired ... ...

Abstract	Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition. Methods: Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures. Results: Peri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count. Discussion: Our topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD. Highlights: Retinal peri-arteriolar region exhibits more amyloid compared with peri-venular regions.Secondary retinal vascular branches have significantly higher perivascular amyloid burden in subjects with impaired cognition, consistent across sexes.Cognitively impaired individuals have significantly greater retinal peri-venular amyloid deposits in the distal small branches, that correlate with CDR and hippocampal volumes.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.27.580733
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Article ; Online: Neurosurgery at the crossroads of immunology and nanotechnology. New reality in the COVID-19 pandemic.

Ljubimov, Vladimir A / Ramesh, Arshia / Davani, Saya / Danielpour, Moise / Breunig, Joshua J / Black, Keith L

Advanced drug delivery reviews

2021 Volume 181, Page(s) 114033

Abstract: Neurosurgery as one of the most technologically demanding medical fields rapidly adapts the newest developments from multiple scientific disciplines for treating brain tumors. Despite half a century of clinical trials, survival for brain primary tumors ... ...

Abstract	Neurosurgery as one of the most technologically demanding medical fields rapidly adapts the newest developments from multiple scientific disciplines for treating brain tumors. Despite half a century of clinical trials, survival for brain primary tumors such as glioblastoma (GBM), the most common primary brain cancer, or rare ones including primary central nervous system lymphoma (PCNSL), is dismal. Cancer therapy and research have currently shifted toward targeted approaches, and personalized therapies. The orchestration of novel and effective blood-brain barrier (BBB) drug delivery approaches, targeting of cancer cells and regulating tumor microenvironment including the immune system are the key themes of this review. As the global pandemic due to SARS-CoV-2 virus continues, neurosurgery and neuro-oncology must wrestle with the issues related to treatment-related immune dysfunction. The selection of chemotherapeutic treatments, even rare cases of hypersensitivity reactions (HSRs) that occur among immunocompromised people, and number of vaccinations they have to get are emerging as a new chapter for modern Nano neurosurgery.
MeSH term(s)	Animals ; Blood-Brain Barrier/surgery ; Brain Neoplasms/surgery ; COVID-19/surgery ; Glioblastoma/surgery ; Humans ; Nanotechnology/methods ; Neurosurgery/methods ; Pandemics/statistics & numerical data ; Tumor Microenvironment/physiology
Language	English
Publishing date	2021-11-20
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2021.114033
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Article ; Online: Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau.

Du, Xiaoxi / Koronyo, Yosef / Mirzaei, Nazanin / Yang, Chengshuai / Fuchs, Dieu-Trang / Black, Keith L / Koronyo-Hamaoui, Maya / Gao, Liang

PNAS nexus

2022 Volume 1, Issue 4, Page(s) pgac164

Abstract: Alzheimer's disease (AD) is a major risk for the aging population. The pathological hallmarks of AD-an abnormal deposition of amyloid β-protein (Aβ) and phosphorylated tau (pTau)-have been demonstrated in the retinas of AD patients, including in ... ...

Abstract	Alzheimer's disease (AD) is a major risk for the aging population. The pathological hallmarks of AD-an abnormal deposition of amyloid β-protein (Aβ) and phosphorylated tau (pTau)-have been demonstrated in the retinas of AD patients, including in prodromal patients with mild cognitive impairment (MCI). Aβ pathology, especially the accumulation of the amyloidogenic 42-residue long alloform (Aβ
Language	English
Publishing date	2022-08-19
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgac164
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Article: Risk management for endowment and foundation portfolios

Black, Keith H

The journal of alternative investments Vol. 15, No. 4 (2012/13), p. 87-96

2013 Volume 15, Issue 4, Page(s) 87–96

Author's details	Keith H. Black
Keywords	Stiftung ; Investmentfonds ; Portfolio-Management ; Anlageverhalten ; Risikomanagement
Language	English
Publisher	Institutional Investor
Publishing place	New York, NY
Document type	Article
ZDB-ID	2049760X
ISSN	1520-3255
Database	ECONomics Information System

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Article: The effects of enhancing angiotensin converting enzyme in myelomonocytes on ameliorating Alzheimer's-related disease and preserving cognition.

Danziger, Ron / Fuchs, Dieu-Trang / Koronyo, Yosef / Rentsendorj, Altan / Sheyn, Julia / Hayden, Eric Y / Teplow, David B / Black, Keith L / Fuchs, Sebastien / Bernstein, Kenneth E / Koronyo-Hamaoui, Maya

Frontiers in physiology

2023 Volume 14, Page(s) 1179315

Abstract: This review examines the role of angiotensin-converting enzyme (ACE) in the context of Alzheimer's disease (AD) and its potential therapeutic value. ACE is known to degrade the neurotoxic 42-residue long alloform of amyloid β-protein ( ... ...

Abstract	This review examines the role of angiotensin-converting enzyme (ACE) in the context of Alzheimer's disease (AD) and its potential therapeutic value. ACE is known to degrade the neurotoxic 42-residue long alloform of amyloid β-protein (Aβ
Language	English
Publishing date	2023-06-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1179315
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Article ; Online: Color and contrast vision in mouse models of aging and Alzheimer's disease using a novel visual-stimuli four-arm maze.

Vit, Jean-Philippe / Fuchs, Dieu-Trang / Angel, Ariel / Levy, Aharon / Lamensdorf, Itschak / Black, Keith L / Koronyo, Yosef / Koronyo-Hamaoui, Maya

Scientific reports

2021 Volume 11, Issue 1, Page(s) 1255

Abstract: We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensity-controlled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Its ... ...

Abstract	We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensity-controlled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Its application to detect visual impairments during normal aging and over the course of Alzheimer's disease (AD) is evaluated in wild-type (WT) and transgenic APP
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Animals ; Color Perception ; Contrast Sensitivity ; Disease Models, Animal ; Hippocampus/physiopathology ; Maze Learning ; Memory ; Mice ; Mice, Transgenic
Language	English
Publishing date	2021-01-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-80988-0
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