The Dynamics of Impaired Blood-Brain Barrier Restoration in a Rat Model of Co-morbid Injury.

Abstract:

:Defect in brain microperfusion is increasingly recognized as an antecedent event to Alzheimer's disease (AD) and ischemia. Nevertheless, studies on the role of impaired microperfusion as a pathological trigger to neuroinflammation, Aβ deposition as well as blood-brain barrier (BBB) disruption, and the etiological link between AD and ischemia are lacking. In this study, we employ in vivo sequential magnetic resonance imaging (MRI) and computed tomography (CT) imaging in a co-morbid rat model of β-amyloid toxicity (Aβ) and ischemia (ET1) with subsequent histopathology of striatal lesion core and penumbra at 1, 7, and 28 days post injury. Within 24 h, cerebral injury resulted in increased BBB permeability due to the dissolution of β-dystroglycan (β-DG) and basement membrane laminin by active matrix metalloproteinase9 (MMP9). As a result, net flow of circulating IgG down a hydrostatic gradient into the parenchyma led to vasogenic edema and impaired perfusion, thus increasing the apparent hyperintensity in true fast imaging with steady-state free precession (true FISP) imaging and acute hypoperfusion in CT. This was followed by a slow recruitment of reactive astroglia to the affected brain and depolarization of aquaporin4 (AQP4) expression resulting in cytotoxic edema-in an attempt to resolve vasogenic edema. On d28, functional BBB was restored in ET1 rats as observed by astrocytic MMP9 release, β-DG stabilization, and new vessel formation. This was confirmed by reduced hyperintensity on true FISP imaging and normalized cerebral blood flow in CT. While, Aβ toxicity alone was not detrimental enough, Aβ+ET1 rats showed delayed differential expression of MMP9, late recruitment of astroglial cells, protracted loss of AQP4 depolarization, and thus delayed BBB restoration and cerebral perfusion.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Amtul Z,Yang J,Nikolova S,Lee TY,Bartha R,Cechetto DF

doi

10.1007/s12035-018-0904-4

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

8071-8083

issue

10

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-0904-4

journal_volume

55

pub_type

杂志文章
  • Agrochemicals, α-synuclein, and Parkinson's disease.

    abstract::Epidemiological, population-based case-control, and experimental studies at the molecular, cellular, and organism levels revealed that exposure to various environmental agents, including a number of structurally different agrochemicals, may contribute to the pathogenesis of Parkinson's disease (PD) and several other n...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-012-8333-2

    authors: Silva BA,Breydo L,Fink AL,Uversky VN

    更新日期:2013-04-01 00:00:00

  • Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction.

    abstract::Long-lasting changes in dendritic spines provide a physical correlate for memory formation and persistence. LIM kinase (LIMK) plays a critical role in orchestrating dendritic actin dynamics during memory processing, since it is the convergent downstream target of both the Rac1/PAK and RhoA/ROCK pathways that in turn i...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0361-x

    authors: Lunardi P,Sachser RM,Sierra RO,Pedraza LK,Medina C,de la Fuente V,Romano A,Quillfeldt JA,de Oliveira Alvares L

    更新日期:2018-02-01 00:00:00

  • Stem Cells as a Promising Tool for the Restoration of Brain Neurovascular Unit and Angiogenic Orientation.

    abstract::Establishing systemic therapeutics for neuro-inflammatory diseases is a main objective of regenerative medicine, certainly focusing on restoration of BBB dysfunction and neurovascular reconstitution. In this context, the regenerative capacity and therapeutic effects of different stem cells have been recently found to ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-016-0286-4

    authors: Geranmayeh MH,Nourazarian A,Avci ÇB,Rahbarghazi R,Farhoudi M

    更新日期:2017-12-01 00:00:00

  • Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury.

    abstract::Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzym...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9118-1

    authors: Chen X,Chen X,Huang X,Qin C,Fang Y,Liu Y,Zhang G,Pan D,Wang W,Xie M

    更新日期:2016-04-01 00:00:00

  • LSD1 is Required for Hair Cell Regeneration in Zebrafish.

    abstract::Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9206-2

    authors: He Y,Tang D,Cai C,Chai R,Li H

    更新日期:2016-05-01 00:00:00

  • Sodium Butyrate, a Histone Deacetylase Inhibitor, Exhibits Neuroprotective/Neurogenic Effects in a Rat Model of Neonatal Hypoxia-Ischemia.

    abstract::Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunctions. Currently, there are no well-established treatments to reduce brain damage and its long-term sequel in infants. Recently, reported data show that histone deacetylase inhibitors...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0049-2

    authors: Ziemka-Nalecz M,Jaworska J,Sypecka J,Polowy R,Filipkowski RK,Zalewska T

    更新日期:2017-09-01 00:00:00

  • Is hypercholesterolemia a risk factor for Alzheimer's disease?

    abstract::There is considerable attention being given to the association of Alzheimer's disease and cholesterol homeostasis. To that end, some have suggested that elevated cholesterol levels are a risk factor for Alzheimer's disease. If elevated cholesterol is a risk factor for Alzheimer's disease, then it would be expected tha...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:31:1-3:185

    authors: Wood WG,Igbavboa U,Eckert GP,Johnson-Anuna LN,Müller WE

    更新日期:2005-01-01 00:00:00

  • Changes in transcriptional factor binding capacity resulting from promoter region methylation induce aberrantly high GDNF expression in human glioma.

    abstract::Glial cell line-derived neurotrophic factor (GDNF), which belongs to transforming growth factor β superfamily, plays important roles in glioma pathogenesis. Gdnf mRNA is aberrantly increased in glioma cells, but the underlying transcription mechanism is unclear. Here, we found that although the base sequence in the pr...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-013-8443-5

    authors: Yu ZQ,Zhang BL,Ren QX,Wang JC,Yu RT,Qu DW,Liu ZH,Xiong Y,Gao DS

    更新日期:2013-12-01 00:00:00

  • The Role of SUMO-Conjugating Enzyme Ubc9 in the Neuroprotection of Isoflurane Preconditioning Against Ischemic Neuronal Injury.

    abstract::Preconditioning with volatile anesthetics can create an ischemia tolerance against cerebral ischemia-reperfusion injury. We investigated whether ubiquitin conjugase 9 (Ubc9), the E2 conjugase for SUMOylation, is associated with neuroprotection induced by isoflurane preconditioning (IsoPC). In vitro, Ubc9 protein expre...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8797-3

    authors: Tong L,Wu Z,Ran M,Chen Y,Yang L,Zhang H,Zhang L,Dong H,Xiong L

    更新日期:2015-01-01 00:00:00

  • Applying imaging genetics to ADHD: the promises and the challenges.

    abstract::Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood psychiatric disorders. During the past decades, studies have focused on its genetic background and the abnormality of the brain structure and function. Recently, an advanced technique linking these two areas, namely, the imaging gen...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-014-8683-z

    authors: Wu Z,Yang L,Wang Y

    更新日期:2014-10-01 00:00:00

  • Analysis of the Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Traumatic Brain and Spinal Cord Injury: Insight into Recent Advances in Actions of Neurochemokine Agents.

    abstract::CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its bi...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-016-9787-4

    authors: Poniatowski ŁA,Wojdasiewicz P,Krawczyk M,Szukiewicz D,Gasik R,Kubaszewski Ł,Kurkowska-Jastrzębska I

    更新日期:2017-04-01 00:00:00

  • Neural Stem Cells from Shank3-ko Mouse Model Autism Spectrum Disorders.

    abstract::Autism spectrum disorders (ASD) comprise a complex of neurodevelopmental disorders caused by a variety of genetic defects and characterized by alterations in social communication and repetitive behavior. Since the mechanisms leading to early neuronal degeneration remain elusive, we chose to examine the properties of N...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-01811-6

    authors: Grasselli C,Carbone A,Panelli P,Giambra V,Bossi M,Mazzoccoli G,De Filippis L

    更新日期:2020-03-01 00:00:00

  • Activity-dependent changes in voltage-dependent calcium currents and transmitter release.

    abstract::Voltage-dependent Ca2+ channels are important in the regulation of neuronal structure and function, and as a result, they have received considerable attention. Recent studies have begun to characterize the diversity of their properties and the relationship of this diversity to their various cellular functions. In part...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02740620

    authors: Lnenicka GA,Hong SJ

    更新日期:1997-02-01 00:00:00

  • MiR-126-3p-Enriched Extracellular Vesicles from Hypoxia-Preconditioned VSC 4.1 Neurons Attenuate Ischaemia-Reperfusion-Induced Pain Hypersensitivity by Regulating the PIK3R2-Mediated Pathway.

    abstract::Recent evidence suggests that hypoxia preconditioning can alter the microRNA (miRNA) profile of extracellular vesicles (EVs) and has better neuroprotective effects when enriched miRs are delivered to recipients. However, the roles of exosomal miRNAs in regulating ischaemia-reperfusion (IR)-induced pain hypersensitivit...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02159-y

    authors: Wang H,Chen FS,Zhang ZL,Zhou HX,Ma H,Li XQ

    更新日期:2021-02-01 00:00:00

  • Quaternary Structure Changes for PrPSc Predate PrPC Downregulation and Neuronal Death During Progression of Experimental Scrapie Disease.

    abstract::Prion diseases are fatal neurodegenerative diseases in mammals with the unique characteristics of misfolding and aggregation of the cellular prion protein (PrPC) to the scrapie prion (PrPSc). Although neuroinflammation and neuronal loss feature within the disease process, the details of PrPC/PrPSc molecular transition...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02112-z

    authors: Eskandari-Sedighi G,Cortez LM,Yang J,Daude N,Shmeit K,Sim V,Westaway D

    更新日期:2021-01-01 00:00:00

  • Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury.

    abstract::Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to impro...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1172-z

    authors: Bucan V,Vaslaitis D,Peck CT,Strauß S,Vogt PM,Radtke C

    更新日期:2019-03-01 00:00:00

  • Phagocytosis of microglia in the central nervous system diseases.

    abstract::Microglia, the resident macrophages of the central nervous system, rapidly activate in nearly all kinds of neurological diseases. These activated microglia become highly motile, secreting inflammatory cytokines, migrating to the lesion area, and phagocytosing cell debris or damaged neurons. During the past decades, th...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-013-8620-6

    authors: Fu R,Shen Q,Xu P,Luo JJ,Tang Y

    更新日期:2014-06-01 00:00:00

  • Olfactory Deprivation Hastens Alzheimer-Like Pathologies in a Human Tau-Overexpressed Mouse Model via Activation of cdk5.

    abstract::Olfactory dysfunction is a recognized risk factor for the pathogenesis of Alzheimer's disease (AD), while the mechanisms are still not clear. Here, we applied bilateral olfactory bulbectomy (OBX), an olfactory deprivation surgery to cause permanent anosmia, in human tau-overexpressed mice (htau mice) to investigate ch...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-9007-z

    authors: Li K,Liu FF,He CX,Huang HZ,Xie AJ,Hu F,Liu D,Wang JZ,Zhu LQ

    更新日期:2016-01-01 00:00:00

  • Interplay between the p53 tumor suppressor protein family and Cdk5: novel therapeutic approaches for the treatment of neurodegenerative diseases using selective Cdk inhibitors.

    abstract::Cyclin-dependent kinases (Cdks) play a key role in orchestrating the coordination of cell cycle progression in proliferating cells. The escape from the proper control of the cell cycle by the upregulation of cyclins or aberrant activation of Cdks leads to malignant transformation. In quiescent cells and/or terminally ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/mn:34:1:27

    authors: Schmid G,Strosznajder JB,Wesierska-Gadek J

    更新日期:2006-08-01 00:00:00

  • Differential Expression of Hippocampal Circular RNAs in the BTBR Mouse Model for Autism Spectrum Disorder.

    abstract::Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with unknown etiology. Recent experimental evidences suggest the contribution of non-coding RNAs (ncRNAs) in the pathophysiology of ASD. In this work, we aimed to investigate the expression profile of the ncRNA class of circular RNAs (circR...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-01878-6

    authors: Gasparini S,Del Vecchio G,Gioiosa S,Flati T,Castrignano T,Legnini I,Licursi V,Ricceri L,Scattoni ML,Rinaldi A,Presutti C,Mannironi C

    更新日期:2020-05-01 00:00:00

  • Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.

    abstract::Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) i...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0524-4

    authors: Beker MC,Caglayan B,Yalcin E,Caglayan AB,Turkseven S,Gurel B,Kelestemur T,Sertel E,Sahin Z,Kutlu S,Kilic U,Baykal AT,Kilic E

    更新日期:2018-03-01 00:00:00

  • Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells.

    abstract::Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0057-2

    authors: Yang H,Liu C,Chen B,An J,Zhang R,Zhang Q,Zhao J,He B,Hao DJ

    更新日期:2017-01-01 00:00:00

  • Antidepressant-Like Effect of Ropren® in β-Amyloid-(25-35) Rat Model of Alzheimer's Disease with Altered Levels of Androgens.

    abstract::This study elucidated the potential antidepressant-like effect of prolonged Ropren® administration (8.6 mg/kg, orally, once daily for 28 days) using a β-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of β-amyloid (25-35) i...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9848-8

    authors: Soultanov V,Fedotova J,Nikitina T,Roschin V,Ordyan N,Hritcu L

    更新日期:2017-05-01 00:00:00

  • Amyotrophic lateral sclerosis and skeletal muscle: an update.

    abstract::Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease characterized by degeneration of upper and lower motor neurons (MNs), generalized weakness and muscle atrophy. The "neurocentric" view of ALS assumes that the disease primarily affects motor neurons, while muscle alterations only...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-013-8578-4

    authors: Pansarasa O,Rossi D,Berardinelli A,Cereda C

    更新日期:2014-04-01 00:00:00

  • Prioritizing Genes Related to Nicotine Addiction Via a Multi-source-Based Approach.

    abstract::Nicotine has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unknown....

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8874-7

    authors: Liu X,Liu M,Li X,Zhang L,Fan R,Wang J

    更新日期:2015-08-01 00:00:00

  • Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1.

    abstract::Smarcd1 is a component of an evolutionary conserved chromatin remodeling complex-SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferati...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02190-z

    authors: Zhu Y,Wang H,Fei M,Tang T,Niu W,Zhang L

    更新日期:2020-11-14 00:00:00

  • Rapid Intracellular Zn2+ Dysregulation via Membrane Corticosteroid Receptor Activation Affects In Vivo CA1 LTP.

    abstract::Involvement of membrane mineralocorticoid (MC) and glucocorticoid (GC) receptors in synaptic Zn2+ dynamics remains unclear. Here, we tested whether synaptic plasticity is affected by rapid intracellular Zn2+ dysregulation via membrane MC and GC receptor activation, in comparison with intracellular Ca2+ dysregulation. ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1159-9

    authors: Suzuki M,Sato Y,Tamura K,Tamano H,Takeda A

    更新日期:2019-02-01 00:00:00

  • Control of receptor sensitivity at the mRNA level.

    abstract::Neurons are able to adjust the sensitivity of receptor-mediated processes according to the level of receptor activation. Extrapolating from our knowledge of other cellular proteins, regulation of receptor mRNA availability would provide a highly economical means of achieving this objective. Epidermal growth factor is ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02769175

    authors: Morris BJ

    更新日期:1993-10-01 00:00:00

  • Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages.

    abstract::The mechanisms by which inflammation affects the different emotional moods are only partially known. Previous works have pointed to stress hormones like glucocorticoids plus the vascular factor endothelin-1 as key factors evoking stressful states especially in relation to endothelial dysfunctions. With this work, it w...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0171-1

    authors: Avolio E,Fazzari G,Mele M,Alò R,Zizza M,Jiao W,Di Vito A,Barni T,Mandalà M,Canonaco M

    更新日期:2017-10-01 00:00:00

  • Presynaptic Regulation of Tonic Inhibition by Neuromodulatory Transmitters in the Basal Amygdala.

    abstract::Tonic inhibition mediated by ambient levels of GABA that activate extrasynaptic GABAA receptors emerges as an essential factor that tunes neuronal network excitability in vitro and shapes behavioral responses in vivo. To address the role of neuromodulatory transmitter systems on this type of inhibition, we employed pa...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-0984-1

    authors: Meis S,Endres T,Munsch T,Lessmann V

    更新日期:2018-11-01 00:00:00