David A. Menassa

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Verified

David verified their affiliation via an institutional email.

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• PhD
• Senior Research Fellow & Lecturer of Neuroscience at University of Oxford

Research is the Titanic, bureaucracy is the iceberg, and we, researchers, are the musicians expected to keep playing as it sinks. Pansieri et al. argue that bureaucracy is suffocating research, as an ever increasing administrative burden consumes researchers’ time and diverts focus from discovery to compliance. They highlight ways in which red tape...

Parkinson's disease (PD) is a complex neurodegenerative disorder characterised by selective neuronal loss. We integrate deep full-length single-nuclei sequencing of the human ventral substantia nigra with genome-wide association studies (GWAS) to reveal genetic and cellular drivers of PD. Genetic risk converges onto AGTR1+ dopaminergic neurons and...

Mapping cellular organization in the developing brain presents significant challenges due to the multidimensional nature of the data, characterized by complex spatial patterns that are difficult to interpret without high-throughput tools. Here, we present DeepCellMap, a deep-learning-assisted tool that integrates multi-scale image processing with a...

Microglia are the brain's resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. How...

Microglia, the brain’s resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in...

Mapping cellular organization in the developing brain presents significant challenges due to the multidimensional nature of the data, characterized by complex spatial patterns that are difficult to interpret without high-throughput tools. We developed DeepCellMap, a deep-learning-assisted tool that integrates multi-scale image processing with advan...

Background Hypothermia is neuroprotective after neonatal hypoxic-ischaemic brain injury. However, systemic cooling to hypothermic temperatures is a stressor and may reduce neuroprotection in awake pigs. We compared two experiments of global hypoxic-ischaemic injury in newborn pigs, in which one group received propofol–remifentanil and the other rem...

Microglia arise from the yolk sac and enter the brain during early embryogenesis. Upon entry, microglia undergo in situ proliferation and eventually colonize the entire brain by the third postnatal week in mice. However, the intricacies of their developmental expansion remain unclear. Here, we characterize the proliferative dynamics of microglia du...

Rodent models of neonatal hypoxic-ischemic (HI) injury require a subset of animals to be immobilized for continuous temperature monitoring during the insult and subsequent treatment. Restrained animals are discarded from the analysis due to the effect of restraint on the brain injury as first demonstrated by Thoresen et al 1996. However, the effect...

Human neurodevelopment is characterised by the appearance, development and disappearance or transformation of various transient structures that underlie the establishment of connectivity within and between future cortical and subcortical areas. Examples of transient structures in the forebrain (amongst many others) include the subpial granular laye...

Microglia are the resident immune cells of the brain and arise from yolk sac-derived macrophages during early embryogenesis. On entering the brain, microglia undergo in situ proliferation and eventually colonise the entire brain by the second and third postnatal weeks in mice. However, the intricate dynamics of their developmental expansion remain...

Microglia are the resident immune cells of the brain and arise from yolk sac-derived macrophages during early embryogenesis. On entering the brain, microglia undergo in situ proliferation and eventually colonise the entire brain by the second and third postnatal weeks in mice. However, the intricate dynamics of their developmental expansion remain...

We study the effect of hypothermia (HT) following hypoxic-ischemic (HI) brain injury in postnatal day 7 (P7) rats. In 2015, new European Union animal transport regulations prompted a change in practice at the breeding facility, which henceforth crossfostered P3 litters to P8 older lactating dam prior to transportation. It is generally assumed that...

Microglia, the brain's resident macrophages, shape neural development and wiring, and are key neuroimmune hubs in the pathological signature of neurodevelopmental disorders. In the human brain, microglial development has not been carefully examined yet, and most of our knowledge derives from rodents. We established an unprecedented collection of 97...

The sustained proliferation of microglia is a key hallmark of Alzheimer’s disease (AD), accelerating its progression. Here, we aim to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesizing that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajector...

Background: Hypothermia-treated and intubated infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) usually receive morphine for sedation and analgesia (SA) during therapeutic hypothermia (TH) and endotracheal ventilation. Altered drug pharmacokinetics in this population increases the risk of drug accumulation. Opioids are neurotoxi...

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high...

The sustained proliferation of microglia is a key hallmark of Alzheimer's disease (AD), accelerating its progression. Here, we sought to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesising that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajec...

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warran...

Improved obstetric and neonatal care have reduced the prevalence of severe hypoxic-ischemic encephalopathy (HIE), however 1-3/1000 newborns in the developed world suffer death or neurodevelopmental disability from HIE. The normal development of the brain during gestation can also be altered by placental reprogramming under oxidative stress. Under t...

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders of genetic and environmental aetiologies. Some ASD cases are syndromic: associated with clinically defined patterns of somatic abnormalities and a neurobehavioural phenotype (e.g. Fragile X syndrome). Many cases, however, are idiopathic or non-syndromic. Such...

Causes of Death

Storage duration, PMI, and brain weight measures

Anteroposterior mapping of the PiC in Nissl sections.

Differences in morphology with Nissl.

Individual neuronal and glial cell densities in layer II.

In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette syndrome or an...

In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette Syndrome or a...

Serum antibodies that bind to the surface of neurons or glia are associated with a wide range of rare but treatable CNS diseases. In many, if not most instances, the serum levels are higher than CSF levels yet most of the reported attempts to reproduce the human disease in mice have used infusion of antibodies into the mouse cerebral ventricle(s) o...

Serum antibodies that bind to the surface of neurons or glia are associated with a wide range of rare but treatable CNS diseases. In many, if not most instances, the serum levels are higher than CSF levels yet most of the reported attempts to reproduce the human disease in mice have used infusion of antibodies into the mouse cerebral ventricle(s) o...

Objective: To identify neuronal surface antibodies in opsoclonus myoclonus ataxia syndrome (OMAS) using contemporary antigen discovery methodology. Methods: OMAS patient serum immunoglobulin G immunohistochemistry using age-equivalent rat cerebellar tissue was followed by immunoprecipitation, gel electrophoresis, and mass spectrometry. Data are...

Microglial cells are thought to colonize the human cerebrum between the 4th and 24th gestational weeks. Rodent studies have demonstrated that these cells originate from yolk sac progenitors though it is not clear whether this directly pertains to human development. Our understanding of microglial cell dynamics in the developing human brain comes mo...

Table S1. Unremarkable investigations in patients. *full blood count, electrolytes, liver function tests, bone profile; **erythrocyte sedimentation rate, C‐reactive protein, antineutrophil cytoplasmic antibodies, antinuclear antibodies; ***Hu, Yo, Ri, CRMP5, glutamic acid decarboxylase, LGI1, CASPR2, MAG, ganglioside screen; ****CMV, EBV, Hepatitis...

St. Catherine of Siena suffered from an extreme form of holy fasting, a condition classified as anorexia mirabilis (also known as inedia prodigiosa). Historical and medical scholarships alike have drawn a comparison between this primaeval type of anorexia with a relatively common form of eating disorder among young women in the modern world, anorex...

Checkpoint-inhibitor medications have revolutionized oncology practice, but frequently induce immune-related adverse events. During autoimmune neurology practice over 20-months, we prospectively identified four patients with likely antibody-mediated neurological diseases after checkpoint-inhibitors: longitudinally extensive transverse myelitis, Gui...

Human autoantibodies to Caspr2 are often associated with neuropathic pain and Caspr2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognised. Human Caspr2 autoantibodies, when injected into mice were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absen...

Autism spectrum disorders (ASDs) are associated with anomalies in time perception. In a perceptual simultaneity task, individuals with ASD demonstrate superior performance compared to typically developing (TD) controls. γ-activity, a robust marker of visual processing, is reportedly altered in ASD in response to a wide variety of tasks and these di...

Gestational transfer of maternal antibodies against fetal neuronal proteins may be relevant to some neurodevelopmental disorders, but until recently there were no proteins identified. We recently reported a fivefold increase in CASPR2-antibodies in mid-gestation sera from mothers of children with intellectual and motor disabilities. Here, we expose...

Background Cycle use across London and the UK has increased considerably over the last 10 years. With this there has been an increased interest in cycle safety and injury prevention. Head injuries are an important cause of mortality and morbidity in cyclists. This study aimed to ascertain the frequency of different head injury types in cyclists and...

Raw data for cyclists included in analysis. (XLSX)

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ mig...

Background CNS disorders can be caused by IgG antibodies to neuronal surface proteins, and these antibodies have the potential to cross the placenta. Since some of them target proteins involved in neurodevelopment, such as contactin-associated protein-2 (CASPR2), we hypothesised that they could alter developing neuronal circuits in utero and lead...

Background: Autism Spectrum Disorder is characterized by sensory anomalies including impaired olfactory identification. 30% of individuals with autism have a clinical diagnosis of epilepsy. Primary olfactory cortex (piriform cortex) is central to olfactory identification and is an epileptogenic structure. Cytoarchitectural changes in olfactory cor...

Autism spectrum disorders (ASD) are neurodevelopmental disorders with multiple neurobiological aetiologies, which could be genetic, structural, metabolic or immune-mediated. ASDs are diagnosed with deficits in social communication and restricted and repetitive behaviours, and are associated with sensorial atypicalities. 30% of cases have co-existin...

Journal Review Article - Antibodies against the β3 subunit of GABAA receptors identified in patients with thymomas. – Spectrum of autoimmune encephalitides extended with discovery of pathogenic antibodies to inhibitory channel. – Identification of antibodies involved a comprehensive characterisation of pathogenicity. – Clinically, improvement is ob...

Ascent to high altitude is associated with a fall in the partial pressure of inspired oxygen (hypobaric hypoxia). For oxidative tissues such as skeletal muscle, resultant cellular hypoxia necessitates acclimatization to optimize energy metabolism and restrict oxidative stress, with changes in gene and protein expression that alter mitochondrial fun...

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The nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and peroxisome proliferator-activated receptor δ (PPARδ) play central roles in regulating metabolism in adipose tissue, as well as being targets for the treatment of insulin resistance. While the role of PPARγ in regulating insulin sensitivity has been well defined, research...

Figure S4 - the effect of PPARγ activation on the integration of the energy metabolism pathways of 3T3-L1 adipocytes. A diagram showing the effect of PPARγ activation on the integration of the energy metabolism pathways of 3T3-L1 adipocytes based on the combination of results from the metabolomic, transcriptomic and stable isotope labeling studies....

Figure S3 - M+1/M isotope ratios. (a, b) The M+1/M isotope ratio 13C enrichment of (a) glutamate and (b) isocitrate analyzed by GC-MS of the aqueous fraction from control and PPARγ agonist-treated 3T3-L1 cells incubated with 13C-U-palmitate. (c-e) Graphs showing the isotope ratio 13C enrichment of myristate (c), arachidate (d) and palmitate (e) ana...