A5018678010- Cerebrospinal fluid and hydrocephalus
- Alzheimer's disease research and treatments
- Intracerebral and Subarachnoid Hemorrhage Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Barrier Structure and Function Studies
- Fetal and Pediatric Neurological Disorders
- Dementia and Cognitive Impairment Research
- Neurological Disease Mechanisms and Treatments
- Neonatal and fetal brain pathology
- Prion Diseases and Protein Misfolding
- Hereditary Neurological Disorders
- Multiple Sclerosis Research Studies
- Spinal Dysraphism and Malformations
- Head and Neck Surgical Oncology
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Peripheral Nerve Disorders
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Hedgehog Signaling Pathway Studies
- Cerebrovascular and genetic disorders
- Botulinum Toxin and Related Neurological Disorders
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
University of Southampton
2012-2021
Southampton General Hospital
2009-2021
University Hospital Southampton NHS Foundation Trust
1978-2017
Moorgreen Hospital
2008
Frenchay Hospital
2001-2008
Center for Neurosciences
2008
Essex Cardiothoracic Centre
1978-2006
Barnard College
2003
University of Utah
2003
Memorial Hospital
2003
Elimination of interstitial fluid and solutes plays a role in homeostasis the brain, but pathways are unclear. Previous work suggests that drains along walls arteries. Aims: to define within capillaries arteries for drainage out brain. Methods: Fluorescent soluble tracers, dextran (3 kDa) ovalbumin (40 kDa), particulate fluospheres (0.02 μm 1.0 diameter) were injected into corpus striatum mice. Brains examined from 5 min 7 days by immunocytochemistry confocal microscopy. Results: tracers...
Cerebrospinal fluid (CSF) drainage pathways from the rat brain were investigated by injection of 50 microliters Indian ink into cisterna magna. The distribution ink, as it escaped cranial CSF space, was documented in 2 mm thick slices and skull cleared cedar wood oil decalcified paraffin sections. Following deep cervical lymph nodes selectively blackened within 30 min lumbar para-aortic 6 h. Within cavity, carbon particles accumulated basal cisterns but also distributed paravascular spaces...
Neuropathological diagnostic criteria for Creutzfeldt‐Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed the following entities: CJD ‐ sporadic, iatrogenic (recognised risk) or familial (same in 1st degree relative): encephalopathy cerebral and/or cerebellar cortex subcortical grey matter; with prion protein (PrP) immuno‐reactivity (plaque diffuse synaptic patchy/perivacuolar types). Gerstmann‐Sträussler‐Scheinker (GSS) (in family...
A major feature of Alzheimer's disease is the accumulation amyloid-β peptide (Aβ) in brain both form plaques cerebral cortex and blood vessel as amyloid angiopathy (CAA). Experimental models human clinical trials have shown that Aβ can be reversed by immunotherapy. In this study, we hypothesized solubilized antibodies generated immunization drains via perivascular pathway, detectable an increase cerebrovascular Aβ. We performed a follow up study patients immunized against Aβ42....
The human brain is the organ with highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that basement membranes of cerebral capillaries and arteries represent pathways along which intramural periarterial drainage (IPAD) soluble metabolites occurs. Failure IPAD could explain vascular deposition amyloid-beta protein as amyloid angiopathy (CAA), key pathological feature Alzheimer's disease. underlying mechanisms...
In the absence of conventional lymphatics, drainage interstitial fluid and solutes from brain parenchyma to cervical lymph nodes is along basement membranes in walls cerebral capillaries tunica media arteries. Perivascular pathways are also involved entry CSF into by convective influx/glymphatic system. The objective this study differentiate vascular membrane which passes out pathway enters brain. Experiment 1: 0.5 µl soluble biotinylated or fluorescent Aβ, 1 15 nm gold nanoparticles was...
Tracers injected into CSF pass the brain alongside arteries and out again. This has been recently termed "glymphatic system" that proposes tracers enter along periarterial "spaces" leave walls of veins. The object present study is to test hypothesis that: (1) from cerebral cortex pial-glial basement membranes as there are no perivascular around cortical arteries, (2) smooth muscle cell form Intramural Peri-Arterial Drainage (IPAD) pathways for elimination interstitial fluid solutes brain. 2...
Antibodies to ubiquitin have been used search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis—motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present all 31 ALS cases but none 23 neurologically normal and only 1 22 controls. These inclusions, which familial sporadic cases, with dementia, took the form dense rounded or irregular ubiquitin-IR cytoplasmic (dense bodies), loosely arranged bundles ('skeins')...
Alzheimer's disease (AD) is characterized by neurofibrillary tangles and the accumulation of β-amyloid (Aβ) peptides in senile plaques walls cortical leptomeningeal arteries as cerebral amyloid angiopathy (CAA). There also a significant increase interstitial fluid (ISF) white matter (WM), pathological basis which largely unknown. We hypothesized that ISF dilated periarterial spaces WM AD correlates with severity CAA, total Aβ load cortex Apo E genotype. A 24 brains 17 nondemented age-matched...
Abstract Alexander disease is a progressive, usually fatal neurological disorder defined by the widespread and abundant presence in astrocytes of protein aggregates called Rosenthal fibers. The most often occurs infants younger than 2 years has been labeled leukodystrophy because an accompanying severe myelin deficit frontal lobes. Later onset forms have also recognized based on In these cases, clinical signs pathology can be quite different from infantile form, raising question whether they...
The objects of the present study were: (1) to define relationships arachnoid mater blood vessels in subarachnoid space; (2) establish structure leptomeningeal trabeculae and their pia mater; (3) investigate fine human mater. Intracranial portions vertebral artery were taken at post mortem, normal cerebral cortex overlying leptomeninges obtained from surgical lobectomies. Tissue these specimens was examined by scanning transmission electron microscopy, light microscopy immunocytochemistry for...