Richard Keep, Ph.D. Publications

2022

Advances in brain barriers and brain fluids research in 2021: great progress in a time of adversity.

Keep RF, Jones HC, Drewes LR.
Fluids Barriers CNS. 2022 Jun 9;19(1):48.
doi: 10.1186/s12987-022-00343-x

A timeline of oligodendrocyte death and proliferation following experimental subarachnoid hemorrhage.

Peng K, Koduri S, Ye F, Yang J, Keep RF, Xi G, Hua Y.
CNS Neurosci Ther. 2022 Jun;28(6):842-850.
doi: 10.1111/cns.13812

Iron-Induced Hydrocephalus: the Role of Choroid Plexus Stromal Macrophages.

Bian C, Wan Y, Koduri S, Hua Y, Keep RF, Xi G.
Transl Stroke Res. 2022 May 11.
doi: 10.1007/s12975-022-01031-6

Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models.

Phillips CM, Stamatovic SM, Keep RF, Andjelkovic AV.
Int J Mol Sci. 2022 Apr 30;23(9):5000.
doi: 10.3390/ijms23095000

Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review. 

Holste KG, Xia F, Ye F, Keep RF, Xi G.
Fluids Barriers CNS. 2022 Apr 1;19(1):28. 
doi: 10.1186/s12987-022-00324-0

Too big, too small: selecting hematoma sizes for inclusion in intracerebral hemorrhage-deferoxamine trials. 

Ye F, Wan Y, Koduri S, Holste KG, Keep RF, Hua Y, Xi G.
Transl Stroke Res. 2022 Mar 28. 
doi: 10.1007/s12975-022-01013-8

Cerebrospinal fluid production by the choroid plexus: a century of barrier research revisited.

MacAulay N, Keep RF, Zeuthen T.
Fluids Barriers CNS. 2022 Mar 22;19(1):26.
doi: 10.1186/s12987-022-00323-1

Delayed Minocycline Treatment Ameliorates Hydrocephalus Development and Choroid Plexus Inflammation in Spontaneously Hypertensive Rats.

Hao X, Ye F, Holste KG, Hua Y, Garton HJL, Keep RF, Xi G.
Int J Mol Sci. 2022 Feb 19;23(4):2306.
doi: 10.3390/ijms23042306

Novel targets, treatments, and advanced models for intracerebral haemorrhage.

Zille M, Farr TD, Keep RF, Römer C, Xi G, Boltze J.
EBioMedicine. 2022 Feb;76:103880.
doi: 10.1016/j.ebiom.2022.103880

The Fate of Erythrocytes after Cerebral Hemorrhage.

Xia F, Keep RF, Ye F, Holste KG, Wan S, Xi G, Hua Y.
Transl Stroke Res. 2022 Jan 23.
doi: 10.1007/s12975-021-00980-8

An In Vivo Mouse Model to Study Blood-Brain Barrier Destabilization in the Chronic Phase of Stroke.

Stamatovic SM, Phillips CM, Keep RF, Andjelkovic AV. 
Methods Mol Biol. 2022;2492:289-305.
doi: 10.1007/978-1-0716-2289-6_17

2021

The Two Faces of Estrogen in Experimental Hemorrhagic Stroke. 

Koduri S, Keep RF, Hua Y, Chaudhary N, Pandey AS, Xi G.
Transl Stroke Res. 2021 Sep 16.
doi: 10.1007/s12975-021-00942-0

Impact of sex differences on thrombin-induced hydrocephalus and white matter injury: the role of neutrophils. 

Peng K, Koduri S, Xia F, Gao F, Hua Y, Keep RF, Xi G.
Fluids Barriers CNS. 2021 Aug 16;18(1):38.
doi: 10.1186/s12987-021-00273-0

Role of Complement Component 3 in Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage. 

Wang M, Xia F, Wan S, Hua Y, Keep RF, Xi G.
Stroke. 2021 Jun 28:STROKEAHA121034372.
doi: 10.1161/STROKEAHA.121.034372

White Matter Survival within and around the Hematoma: Quantification by MRI in Patients with Intracerebral Hemorrhage. 

Novakovic N, Linzey JR, Chenevert TL, Gemmete JJ, Troost JP, Xi G, Keep RF, Pandey AS, Chaudhary N.
Biomolecules. 2021 Jun 18;11(6):910.
doi: 10.3390/biom11060910

Assessing early erythrolysis and the relationship to perihematomal iron overload and white matter survival in human intracerebral hemorrhage. 

Novakovic N, Wilseck ZM, Chenevert TL, Xi G, Keep RF, Pandey AS, Chaudhary N.
CNS Neurosci Ther. 2021 Jun 17.
doi: 10.1111/cns.13693

Acute T2*-Weighted Magnetic Resonance Imaging Detectable Cerebral Thrombosis in a Rat Model of Subarachnoid Hemorrhage. 

Zhang J, Peng K, Ye F, Koduri S, Hua Y, Keep RF, Xi G.
Transl Stroke Res. 2021 Jun 2.
doi: 10.1007/s12975-021-00918-0

Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.

Keep RF, Jones HC, Drewes LR.
Fluids Barriers CNS. 2021 May 21;18(1):24.
doi: 10.1186/s12987-021-00258-z

Acute micro-thrombosis after subarachnoid hemorrhage: A new therapeutic target?

Ye F, Keep RF, Hua Y, Garton HJ, Xi G.
J Cereb Blood Flow Metab. 2021 May 17:271678X211013595.
doi: 10.1177/0271678X211013595

CD47 blocking antibody accelerates hematoma clearance and alleviates hydrocephalus after experimental intraventricular hemorrhage. 

Ye F, Hua Y, Keep RF, Xi G, Garton HJL.
Neurobiol Dis. 2021 May 1:105384.
doi: 10.1016/j.nbd.2021.105384

Hydrocephalus Induced by Intraventricular Peroxiredoxin-2: The Role of Macrophages in the Choroid Plexus. 

Chen T, Tan X, Xia F, Hua Y, Keep RF, Xi G.
Biomolecules. 2021 Apr 29;11(5):654.
doi: 10.3390/biom11050654

Hydrocephalus Following Experimental Subarachnoid Hemorrhage in Rats with Different Aerobic Capacity. 

Toyota Y, Shishido H, Ye F, Koch LG, Britton SL, Garton HJL, Keep RF, Xi G, Hua Y.
Int J Mol Sci. 2021 Apr 26;22(9):4489.
doi: 10.3390/ijms22094489

Cerebrospinal Fluid from Aneurysmal Subarachnoid Hemorrhage Patients Leads to Hydrocephalus in Nude Mice. 

Wan S, Wei J, Hua Y, Koduri S, Keep RF, Xi G, Pandey AS.
Neurocrit Care. 2021 Apr;34(2):423-431.
doi: 10.1007/s12028-020-01031-0

Ten Years and Counting: a Celebration of the 10th Anniversary of Translational Stroke Research. 

Keep RF, Xi G.
Transl Stroke Res. 2021 Feb 27.
doi: 10.1007/s12975-021-00902-8

The role of complement in brain injury following intracerebral hemorrhage: A review. 

Holste K, Xia F, Garton HJL, Wan S, Hua Y, Keep RF, Xi G.
Exp Neurol. 2021 Feb 19:113654. 
doi: 10.1016/j.expneurol.2021.113654

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

Boltze J, Aronowski JA, Badaut J, Buckwalter MS, Caleo M, Chopp M, Dave KR, Didwischus N, Dijkhuizen RM, Doeppner TR, Dreier JP, Fouad K, Gelderblom M, Gertz K, Golubczyk D, Gregson BA, Hamel E, Hanley DF, Härtig W, Hummel FC, Ikhsan M, Janowski M, Jolkkonen J, Karuppagounder SS, Keep RF, Koerte IK, Kokaia Z, Li P, Liu F, Lizasoain I, Ludewig P, Metz GAS, Montagne A, Obenaus A, Palumbo A, Pearl M, Perez-Pinzon M, Planas AM, Plesnila N, Raval AP, Rueger MA, Sansing LH, Sohrabji F, Stagg CJ, Stetler RA, Stowe AM, Sun D, Taguchi A, Tanter M, Vay SU, Vemuganti R, Vivien D, Walczak P, Wang J, Xiong Y, Zille M.
Front Aging Neurosci. 2021 Jan 28;13:623751.
doi: 10.3389/fnagi.2021.623751

Ultra-Early Cerebral Thrombosis Formation After Experimental Subarachnoid Hemorrhage Detected on T2* Magnetic Resonance Imaging. 

Wang Z, Chen J, Toyota Y, Keep RF, Xi G, Hua Y.
Stroke. 2021 Feb 4:STROKEAHA120032397. 
doi: 10.1161/STROKEAHA.120.032397

2020

Role of lipocalin-2 in extracellular peroxiredoxin 2-induced brain swelling, inflammation and neuronal death.

Zhang J, Novakovic N, Hua Y, Keep RF, Xi G.
Exp Neurol. 2020 Oct 29;335:113521.
doi: 10.1016/j.expneurol.2020.113521

Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage. 

Chen J, Koduri S, Dai S, Toyota Y, Hua Y, Chaudhary N, Pandey AS, Keep RF, Xi G.
Transl Stroke Res. 2020 Oct 22.
doi: 10.1007/s12975-020-00870-5

White matter T2 hyperintensities and blood-brain barrier disruption in the hyperacute stage of subarachnoid hemorrhage in male mice: The role of lipocalin-2. 

Toyota Y, Wei J, Xi G, Keep RF, Hua Y.
CNS Neurosci Ther. 2019 Oct;25(10):1207-1214. 
doi: 10.1111/cns.13221

Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin. 

Wan Y, Hua Y, Garton HJL, Novakovic N, Keep RF, Xi G.
CNS Neurosci Ther. 2019 Oct;25(10):1134-1141. 
doi: 10.1111/cns.13203

Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage.

Wei J, Wang M, Jing C, Keep RF, Hua Y, Xi G.
Transl Stroke Res. 2020 Oct;11(5):1095-1102
DOI: 10.1007/s12975-020-00790-4

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke.

Ye F, Garton HJL, Hua Y, Keep RF, Xi G.
Transl Stroke Res. 2020 Sep 29.
DOI: 10.1007/s12975-020-00855-4

Mechanisms of Post-Hemorrhagic Stroke Hydrocephalus Development: The Role of Kolmer Epiplexus Cells. 

Koduri S, Daou B, Hua Y, Keep R, Xi G, Pandey AS.
World Neurosurg. 2020 Sep 28;144:256-257. 
doi: 10.1016/j.wneu.2020.09.121

Perihematomal brain tissue iron concentration measurement by MRI in patients with intracerebral hemorrhage.

Wei J, Novakovic N, Chenevert TL, Xi G, Keep RF, Pandey AS, Chaudhary N.
CNS Neurosci Ther. 2020 Sep;26(9):896-901.
DOI: 10.1111/cns.13395

Publisher Correction: Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury.

Shi Y, Zhang L, Pu H, Mao L, Hu X, Jiang X, Xu N, Stetler RA, Zhang F, Liu X, Leak RK, Keep RF, Ji X, Chen J.
Nat Commun. 2020 Aug 25;11(1):4335.
Erratum for: Nat Commun. 2016 Jan 27;7:10523.
DOI: 10.1038/s41467-020-18263-5

A novel approach to treatment of thromboembolic stroke in mice: Redirecting neutrophils toward a peripherally implanted CXCL1-soaked sponge.

Stamatovic SM, Phillips CM, Keep RF, Andjelkovic AV.
Exp Neurol. 2020 Aug;330:113336.
DOI: 10.1016/j.expneurol.2020.113336

Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms.

Andjelkovic AV, Stamatovic SM, Phillips CM, Martinez-Revollar G, Keep RF.
Fluids Barriers CNS. 2020 Jul 16;17(1):44.
DOI: 10.1186/s12987-020-00202-7

Cerebrospinal Fluid from Aneurysmal Subarachnoid Hemorrhage Patients Leads to Hydrocephalus in Nude Mice.

Wan S, Wei J, Hua Y, Koduri S, Keep RF, Xi G, Pandey AS.
Neurocrit Care. 2020 Jul 1.
DOI: 10.1007/s12028-020-01031-0

CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats.

Tao C, Keep RF, Xi G, Hua Y.
Transl Stroke Res. 2020 Jun;11(3):541-551.
DOI: 10.1007/s12975-019-00745-4

Prx2 (Peroxiredoxin 2) as a Cause of Hydrocephalus After Intraventricular Hemorrhage.

Tan X, Chen J, Keep RF, Xi G, Hua Y.
Stroke. 2020 May;51(5):1578-1586
DOI: 10.1161/STROKEAHA.119.028672

Discovery and Optimization of Triazine Nitrile Inhibitors of Toxoplasma gondii Cathepsin L for the Potential Treatment of Chronic Toxoplasmosis in the CNS.

Zwicker JD, Smith D, Guerra AJ, Hitchens JR, Haug N, Vander Roest S, Lee P, Wen B, Sun D, Wang L, Keep RF, Xiang J, Carruthers VB, Larsen SD.
ACS Chem Neurosci. 2020 Aug 19;11(16):2450-2463
DOI: 10.1021/acschemneuro.9b00674

Intracerebral Hemorrhage-Induced Brain Injury in Rats: the Role of Extracellular Peroxiredoxin 2.

Bian L, Zhang J, Wang M, Keep RF, Xi G, Hua Y.
Transl Stroke Res. 2020 Apr;11(2):288-295.
DOI: 10.1007/s12975-019-00714-x

Recommendations for Clinical Trials in ICH: The Second Hemorrhagic Stroke Academia Industry Roundtable.

Hemorrhagic Stroke Academia Industry (HEADS) Roundtable Participants; Second HEADS Roundtable Participants.
Stroke. 2020 Apr;51(4):1333-1338
DOI: 10.1161/STROKEAHA.119.027882

This was the year that was: brain barriers and brain fluid research in 2019.

Keep RF, Jones HC, Drewes LR.
Fluids Barriers CNS. 2020 Mar 5;17(1):20.
DOI: 10.1186/s12987-020-00181-9

Effects of aging on hydrocephalus after intraventricular hemorrhage.

Wan Y, Gao F, Ye F, Yang W, Hua Y, Keep RF, Xi G.
Fluids Barriers CNS. 2020 Feb 28;17(1):8.
DOI: 10.1186/s12987-020-0169-y

CNS fluid and solute movement: physiology, modelling and imaging.

Jones HC, Keep RF, Drewes LR.
Fluids Barriers CNS. 2020 Feb 4;17(1):12.
DOI: 10.1186/s12987-020-0174-1

2019

Involvement of human and canine MRP1 and MRP4 in benzylpenicillin transport.

Zhao X, Li Y, Du K, Wu Y, Liu L, Cui S, Zhang Y, Gao J, Keep RF, Xiang J.
PLoS One. 2019 Nov 27;14(11):e0225702.
DOI: 10.1371/journal.pone.0225702

Endothelial targets in stroke: Translating animal models to human.

Andjelkovic AV, Xiang J, Stamatovic SM, Hua Y, Xi G, Wang MM, Keep RF.
Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2240-2247.
DOI: 10.1161/ATVBAHA.119.312816

Effects of minocycline on epiplexus macrophage activation, choroid plexus injury and hydrocephalus development in spontaneous hypertensive rats.

Gu C, Hao X, Li J, Hua Y, Keep RF, Xi G.
J Cereb Blood Flow Metab. 2019 Oct;39(10):1936-1948.
DOI: 10.1177/0271678X19836117

Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin.

Wan Y, Hua Y, Garton HJL, Novakovic N, Keep RF, Xi G.
CNS Neurosci Ther. 2019 Oct;25(10):1134-1141.
DOI: 10.1111/cns.13203

Unexpected encounters at the crossroads: Intersections between dopamine, the immune system and psychiatric disorders at the blood-CSF barrier.

Keep RF, Xiang J.
Brain Behav Immun. 2019 Oct;81:20-21.
DOI: 10.1016/j.bbi.2019.07.030

White matter T2 hyperintensities and blood-brain barrier disruption in the hyperacute stage of subarachnoid hemorrhage in male mice: The role of lipocalin-2.

Toyota Y, Wei J, Xi G, Keep RF, Hua Y.
CNS Neurosci Ther. 2019 Oct;25(10):1207-1214.
DOI: 10.1111/cns.13221

Response by Hua et al to Letter Regarding Article, "Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage".

Hua Y, Keep RF, Xi G.
Stroke. 2019 Sep;50(9):e266.
DOI: 10.1161/STROKEAHA.119.026620

Correction to: Intracerebral Hemorrhage-Induced Brain Injury in Rats: the Role of Extracellular Peroxiredoxin 2.

Bian L, Zhang J, Wang M, Keep RF, Xi G, Hua Y.
Transl Stroke Res. 2019 Aug 9.
Erratum for: Transl Stroke Res. 2019 Jul 4
DOI: 10.1007/s12975-019-00720-z

Deferoxamine therapy reduces brain hemin accumulation after intracerebral hemorrhage in piglets.

Hu S, Hua Y, Keep RF, Feng H, Xi G.
Exp Neurol. 2019 Aug;318:244-250.
DOI: 10.1016/j.expneurol.2019.05.003

Involvement of Epigenetic Mechanisms and Non-coding RNAs in Blood-Brain Barrier and Neurovascular Unit Injury and Recovery After Stroke.

Stamatovic SM, Phillips CM, Martinez-Revollar G, Keep RF, Andjelkovic AV.
Front Neurosci. 2019 Aug 20;13:864.
DOI: 10.3389/fnins.2019.00864

Complement Inhibition Attenuates Early Erythrolysis in the Hematoma and Brain Injury in Aged Rats.

Wang M, Hua Y, Keep RF, Wan S, Novakovic N, Xi G.
Stroke. 2019 Jul;50(7):1859-1868.
DOI: 10.1161/STROKEAHA.119.025170

The effect of aging on brain injury and recovery after stroke.

Baltan S, Shi Y, Keep RF, Chen J.
Neurobiol Dis. 2019 Jun;126:1-2.
DOI: 10.1016/j.nbd.2019.04.001

Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage.

Jing C, Bian L, Wang M, Keep RF, Xi G, Hua Y.
Stroke. 2019 Jun;50(6):1539-1547.
DOI: 10.1161/STROKEAHA.118.024578

Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

Dai S, Hua Y, Keep RF, Novakovic N, Fei Z, Xi G.
Neurobiol Dis. 2019 Jun;126:76-84.
DOI: 10.1016/j.nbd.2018.06.001

The effect of age-related risk factors and comorbidities on white matter injury and repair after ischemic stroke.

Xu M, Wang MM, Gao Y, Keep RF, Shi Y.
Neurobiol Dis. 2019 Jun;126:13-22.
DOI: 10.1016/j.nbd.2018.07.008

Decline in Sirtuin-1 expression and activity plays a critical role in blood-brain barrier permeability in aging.

Stamatovic SM, Martinez-Revollar G, Hu A, Choi J, Keep RF, Andjelkovic AV.
Neurobiol Dis. 2019 Jun;126:105-116.
DOI: 10.1016/j.nbd.2018.09.006

Brain tissue iron quantification by MRI in intracerebral hemorrhage: Current translational evidence and pitfalls.

Chaudhary N, Pandey AS, Griauzde J, Gemmete JJ, Chenevert TL, Keep RF, Xi G.
J Cereb Blood Flow Metab. 2019 Mar;39(3):562-564.
DOI: 10.1177/0271678X18818911

The year in review: progress in brain barriers and brain fluid research in 2018.

Keep RF, Jones HC, Drewes LR.
Fluids Barriers CNS. 2019 Feb 5;16(1):4.
DOI: 10.1186/s12987-019-0124-y

Histidine-rich Glycoprotein Could Be an Early Predictor of Vasospasm after Aneurysmal Subarachnoid Hemorrhage.

Matsumoto A, Nakamura T, Shinomiya A, Kawakita K, Kawanishi M, Miyake K, Kuroda Y, Keep RF, Tamiya T.
Acta Med Okayama. 2019 Feb;73(1):29-39.
DOI: 10.18926/AMO/56456

Brain Ceruloplasmin Expression After Experimental Intracerebral Hemorrhage and Protection Against Iron-Induced Brain Injury.

Liu H, Hua Y, Keep RF, Xi G.
Transl Stroke Res. 2019 Feb;10(1):112-119.
DOI: 10.1007/s12975-018-0669-0

Early Hemolysis Within Human Intracerebral Hematomas: an MRI Study.

Liu R, Li H, Hua Y, Keep RF, Xiao J, Xi G, Huang Y.
Transl Stroke Res. 2019 Feb;10(1):52-56.
DOI: 10.1007/s12975-018-0630-2

Claudin-1-Dependent Destabilization of the Blood-Brain Barrier in Chronic Stroke.

Sladojevic N, Stamatovic SM, Johnson AM, Choi J, Hu A, Dithmer S, Blasig IE, Keep RF, Andjelkovic AV.
J Neurosci. 2019 Jan 23;39(4):743-757.
DOI: 10.1523/JNEUROSCI.1432-18.2018


Richard Keep, Ph.D.

Director, Crosby Neurosurgical Laboratories
Associate Chair for Research, Neurosurgery
Crosby-Kahn Collegiate Professor of Neurosurgery and Neuroanatomy
Professor, Molecular and Integrative Physiology
734-764-5128