Ross Nortley's research while affiliated with University College London and other places

Publications (8)

Article
Cerebral blood flow is reduced early in Alzheimer’s disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. Here we used live and rapidly-fixed biopsied human tissue to establish disease-relevance, and rodent experiments to define mechanism...
Article
Full-text available
Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood–brain barrier. Pericytes, an under-studied cell type located on capillaries, ar...
Preprint
Full-text available
Vascular compromise occurs early in Alzheimer's disease (AD) and other dementias. Amyloid β (Aβ) reduces cerebral blood flow and, as most of the cerebral vasculature resistance is in capillaries, Aβ might mainly act on contractile pericytes on capillary walls. Employing human tissue to establish disease-relevance, and rodent experiments to define m...
Article
Astrocytes form an anatomical bridge between the vasculature and neuronal synapses. Recent work suggests that they play a key role in regulating brain energy supply by increasing blood flow to regions where neurons are active, and setting the baseline level of blood flow. Controversy persists over whether lactate derived from astrocyte glycolysis i...
Chapter
A 61 year old man presents with slowly progressive balance difficulties and numbness in the lower limbs. Neurological examination is consistent with a sensory ataxia. Investigations reveal positive anti-GD1b antibodies with modestly elevated CSF protein. EMG and nerve conduction studies demonstrate a mild large-fibre axonal motor-sensory neuropathy...
Article
We describe two women presenting with severe postpartum headache associated with hypertension but with no other signs or investigation results to suggest pre-eclampsia. In one case, the headache was associated with atypical subarachnoid haemorrhage. The variable nature of the headache and the degree of associated hypertension raised the clinical su...
Article
A 54-year-old woman diagnosed with primary Sjögren's syndrome in 2007 presented with a 1-year history of visual hallucinations requiring admission to a psychiatric unit. The hallucinations resolved while on olanzapine and hydroxychloroquine but recurred when they were stopped. Despite restarting olanzapine, her visual hallucinations persisted. When...
Article
A 55-year-old man with a history of sickle cell disease (sickle cell hemoglobin C) but no history of sickle cell crises was seen with an episode of acute abdominal pain and fever. He had no significant medical history, including no antecedent neurologic problems. He became unresponsive during 24 hours, necessitating intubation and ventilation. On e...

Citations

... Some aspects of the microglial metabolic signature certainly recapitulate that of peripheral immune cells, but the unique metabolic conditions encountered in the brain parenchyma establishes a brain-specific form of metabolic flexibility. It is now believed that impaired energy metabolism and altered cerebrovascular mechanisms accompany, and possibly directly contribute to most neurodegenerative diseases [103][104][105] . Whether in chronic brain disorders or in acute metabolic stress, a better understanding of the specific energy requirements of microglia will have key clinical implications for neuronal function and brain health. ...
... En algunos estudios previamente publicados se ha descrito la presencia de lesiones cerebrales similares asociadas con enfermedades críticas, incluyendo la insuficiencia respiratoria, la encefalitis infecciosa o la enfermedad de células falciformes 6 . Sin embargo, en la mayoría de estos estudios los análisis de laboratorio mostraban el desarrollo de una CID, lo que sugiere un mecanismo subyacente compartido. ...
... Once myelin is formed, astrocytes further play a role in myelin plasticity by regulating myelin thickness and nodal gap length (Dutta et al., 2018). Lastly, astrocytes control local blood flow depending on neuronal activity (for review, Nortley and Attwell, 2017) and could thus further be involved Astrocytes release factors regulating OPC proliferation (1). Neuronal activity triggers LIF release by astrocytes (2), which promotes myelination (3). ...
... Animal models of epileptogenesis, in particular rats or mice exposed to de novo status epilepticus evoked by electrical stimulation or by chemoconvulsive drugs, share a common neuroinflammatory response in brain areas affected by the primary injury. This fast onset response (within minutes) involves the release of inflammatory molecules generated by activated glial cells, neurons and cellular components of the blood brain barrier (BBB) such as pericytes, glia and endothelial cells (Cheng et al., 2018;Marchi and Lerner-Natoli, 2013;Giannoni et al., 2018;van Vliet et al., 2018;Klement et al., 2019). This event is associated with induction of the receptors for the inflammatory mediators, and the consequent activation of the associated intracellular pathways in the target cells (e.g., glia, neurons and BBB components). ...
... 47 Headache can be treated with calcium channel blockers (nimodipine), but symptoms may resolve without treatment, especially if any precipitant is removed. 48 ...