Correction: Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy
Nimmo JT, Verma A, Dodart JC, Wang CY, Savistchenko J, Melki R, Carare RO and Nicoll JAR
Correction: Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy
Nimmo JT, Verma A, Dodart JC, Wang CY, Savistchenko J, Melki R, Carare RO and Nicoll JAR
Harboring Cnm-expressing Streptococcus mutans in the oral cavity relates to both deep and lobar cerebral microbleeds
Ikeda S, Saito S, Hosoki S, Tonomura S, Yamamoto Y, Ikenouchi H, Ishiyama H, Tanaka T, Hattori Y, Friedland RP, Carare RO, Kuriyama N, Yakushiji Y, Hara H, Koga M, Toyoda K, Nomura R, Takegami M, Nakano K and Ihara M
Harboring Cnm-expressing Streptococcus mutans in the oral cavity relates to both deep and lobar cerebral microbleeds
Ikeda S, Saito S, Hosoki S, Tonomura S, Yamamoto Y, Ikenouchi H, Ishiyama H, Tanaka T, Hattori Y, Friedland RP, Carare RO, Kuriyama N, Yakushiji Y, Hara H, Koga M, Toyoda K, Nomura R, Takegami M, Nakano K and Ihara M
Cerebral microbleeds (CMBs) influence long-term prognoses of stroke patients. Streptococcus mutans, a major cariogenic bacterium that expresses the collagen-binding protein Cnm, induces cerebrovascular inflammation, impairing blood brain barrier integrity and causing cerebral bleeding. Here, we examine the association of Cnm-positive S. mutans with CMBs.
The impairment of intramural periarterial drainage in brain after subarachnoid hemorrhage
Sun Y, Liu E, Pei Y, Yao Q, Ma H, Mu Y, Wang Y, Zhang Y, Yang X, Wang X, Xue J, Zhai J, Carare RO, Qin L and Yan J
The impairment of intramural periarterial drainage in brain after subarachnoid hemorrhage
Sun Y, Liu E, Pei Y, Yao Q, Ma H, Mu Y, Wang Y, Zhang Y, Yang X, Wang X, Xue J, Zhai J, Carare RO, Qin L and Yan J
Interstitial fluid (ISF) from brain drains along the basement membranes of capillaries and arteries as Intramural Periarterial Drainage (IPAD); failure of IPAD results in cerebral amyloid angiopathy (CAA). In this study, we test the hypothesis that IPAD fails after subarachnoid haemorrhage (SAH). The rat SAH model was established using endovascular perforation method. Fluorescence dyes with various molecular weights were injected into cisterna magna of rats, and the pattern of IPAD after SAH was detected using immunofluorescence staining, two-photon fluorescent microscope, transmission electron microscope and magnetic resonance imaging tracking techniques. Our results showed that fluorescence dyes entered the brain along a periarterial compartment and were cleared from brain along the basement membranes of the capillaries, with different patterns based on individual molecular weights. After SAH, there was significant impairment in the IPAD system: marked expansion of perivascular spaces, and ISF clearance rate was significantly decreased, associated with the apoptosis of endothelial cells, activation of astrocytes, over-expression of matrix metalloproteinase 9 and loss of collagen type IV. In conclusion, experimental SAH leads to a failure of IPAD, clinically significant for long term complications such as CAA, following SAH.
Author Response: Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study
Piazza F, Basso G, Pascarella R, Carare RO and Zedde M
Author Response: Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study
Piazza F, Basso G, Pascarella R, Carare RO and Zedde M
Quantifying cerebrospinal fluid dynamics: A review of human neuroimaging contributions to CSF physiology and neurodegenerative disease
Mehta NH, Suss RA, Dyke JP, Theise ND, Chiang GC, Strauss S, Saint-Louis L, Li Y, Pahlajani S, Babaria V, Glodzik L, Carare RO and de Leon MJ
Quantifying cerebrospinal fluid dynamics: A review of human neuroimaging contributions to CSF physiology and neurodegenerative disease
Mehta NH, Suss RA, Dyke JP, Theise ND, Chiang GC, Strauss S, Saint-Louis L, Li Y, Pahlajani S, Babaria V, Glodzik L, Carare RO and de Leon MJ
Cerebrospinal fluid (CSF), predominantly produced in the ventricles and circulating throughout the brain and spinal cord, is a key protective mechanism of the central nervous system (CNS). Physical cushioning, nutrient delivery, metabolic waste, including protein clearance, are key functions of the CSF in humans. CSF volume and flow dynamics regulate intracranial pressure and are fundamental to diagnosing disorders including normal pressure hydrocephalus, intracranial hypotension, CSF leaks, and possibly Alzheimer's disease (AD). The ability of CSF to clear normal and pathological proteins, such as amyloid-beta (Aβ), tau, alpha synuclein and others, implicates it production, circulation, and composition, in many neuropathologies. Several neuroimaging modalities have been developed to probe CSF fluid dynamics and better relate CSF volume and flow to anatomy and clinical conditions. Approaches include 2-photon microscopic techniques, MRI (tracer-based, gadolinium contrast, endogenous phase-contrast), and dynamic positron emission tomography (PET) using existing approved radiotracers. Here, we discuss CSF flow neuroimaging, from animal models to recent clinical-research advances, summarizing current endeavors to quantify and map CSF flow with implications towards pathophysiology, new biomarkers, and treatments of neurological diseases.
α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression
Hawkes CA, Heath CJ, Sharp MM, Górecki DC and Carare RO
α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression
Hawkes CA, Heath CJ, Sharp MM, Górecki DC and Carare RO
α-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems.
Decreased CSF clearance and increased brain amyloid in Alzheimer's disease
Li Y, Rusinek H, Butler T, Glodzik L, Pirraglia E, Babich J, Mozley PD, Nehmeh S, Pahlajani S, Wang X, Tanzi EB, Zhou L, Strauss S, Carare RO, Theise N, Okamura N and de Leon MJ
Decreased CSF clearance and increased brain amyloid in Alzheimer's disease
Li Y, Rusinek H, Butler T, Glodzik L, Pirraglia E, Babich J, Mozley PD, Nehmeh S, Pahlajani S, Wang X, Tanzi EB, Zhou L, Strauss S, Carare RO, Theise N, Okamura N and de Leon MJ
In sporadic Alzheimer's disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living humans. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. MRI phase contrast and intrathecally delivered contrast studies have reported reduced CSF flow in AD. Using PET and tau tracer F-THK5117, we previously reported that the ventricular CSF clearance of the PET tracer was reduced in AD and associated with elevated brain Aβ levels.
In silico exploration of amyloid-related imaging abnormalities in the gantenerumab open-label extension trials using a semi-mechanistic model
Aldea R, Grimm HP, Gieschke R, Hofmann C, Lott D, Bullain S, Delmar P, Klein G, Lyons M, Piazza F, Carare RO and Mazer NA
In silico exploration of amyloid-related imaging abnormalities in the gantenerumab open-label extension trials using a semi-mechanistic model
Aldea R, Grimm HP, Gieschke R, Hofmann C, Lott D, Bullain S, Delmar P, Klein G, Lyons M, Piazza F, Carare RO and Mazer NA
Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) are commonly observed with anti-amyloid therapies in Alzheimer's disease. We developed a semi-mechanistic, in silico model to understand the time course of ARIA-E and its dose dependency.
The Lymphatic System in Neurological Disease and Alzheimer's Disease. A Brief Editorial
Pappolla MA, Carare RO, Poeggeler B, Wisniewski T and Sambamurti K
The Lymphatic System in Neurological Disease and Alzheimer's Disease. A Brief Editorial
Pappolla MA, Carare RO, Poeggeler B, Wisniewski T and Sambamurti K
Translation of the Fugl-Meyer assessment into Romanian: Transcultural and semantic-linguistic adaptations and clinical validation
Onose G, Anghelescu A, Ionescu A, Tataranu LG, Spînu A, Bumbea AM, Toader C, Tuţă S, Carare RO, Popescu C, Munteanu C, and Daia C
Translation of the Fugl-Meyer assessment into Romanian: Transcultural and semantic-linguistic adaptations and clinical validation
Onose G, Anghelescu A, Ionescu A, Tataranu LG, Spînu A, Bumbea AM, Toader C, Tuţă S, Carare RO, Popescu C, Munteanu C, and Daia C
The Fugl-Meyer Assessment (FMA) scale, which is widely used and highly recommended, is an appropriate tool for evaluating poststroke sensorimotor and other possible somatic deficits. It is also well-suited for capturing a dynamic rehabilitation process. The aim of this study was to first translate the entire sensorimotor FMA scale into Romanian using the transcultural and semantic-linguistic adaptations of its official afferent protocols and to validate it using the preliminary clinical evaluation of inter- and intra-rater reliability and relevant concurrent validity.