Gavin Woodhall

Professor, Aston Pharmacy School Aston University

  • Birmingham

Professor Woodhall researches electrophysiological studies on neurones of the entorhinal cortex (EC) and the hippocampus.

Contact

Aston University

View more experts managed by Aston University

Spotlight

3 min

Researchers reveal CBD can counter epileptic seizures in children

Aston University epilepsy model used to illustrate the mechanisms of seizure activity Results suggest how CBD can be useful in the treatment of childhood epilepsy New insight into potential future interventions for hard-to-treat epilepsy. Researchers at Aston University have contributed to the discovery of a previously unknown way in which cannabidiol (CBD), a non-psychoactive component of cannabis, can reduce seizures in many treatment-resistant forms of childhood epilepsy. A group of international collaborators, led by scientists at NYU Grossman School of Medicine, including a team from the Aston Institute of Health and Neurodevelopment at Aston University, found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI). LPI is found in our brain’s neurons and is thought to amplify nerve signals as part of normal function but can be hijacked by some epilepsies to promote seizures. The study, published in the journal Neuron, expanded on previous findings showing that CBD blocks the ability of the molecule LPI to amplify nerve signals in a brain region called the hippocampus. The current study argues that, for the first time, the molecule also weakens signals that counter seizures, further explaining the value of CBD treatment and the generation of seizure activity in epileptic people. As part of the research group, the Aston University team used a leading model of epilepsy, developed by Professor Gavin Woodhall, to perform recordings of electrical signals in brain cells taken from epileptic rodents, some of which had been treated with CBD. By doing this, they were able to pinpoint the molecular mechanisms by which CBD acts to prevent seizure activity in epileptic brains. Professor Woodhall, co-director of Aston Institute for Health and Neurodevelopment, said: “These new insights into epilepsy and the mechanism by which CBD works to stop seizures is the fruit of years of collaboration between neuroscientists in the UK and USA and our industry partner, GW Pharma. We are hopeful that it will lead to even better treatments in future”. Dr Stuart Greenhill, senior lecturer in neuroscience, Aston Institute for Health and Neurodevelopment added: "We are delighted that our epilepsy model is being used to make such meaningful breakthroughs in the mechanisms of epilepsy and is paving the way for a wider range of future treatments". Corresponding author Richard W Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health, said: “Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches. “The study also clarified, not just how CBD counters seizures, but more broadly how circuits are balanced in the brain. Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact.” The results build on how each neuron “fires” to send an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects it to the next cell in a neuronal pathway, and how this activity can change in a network which is likely to generate epileptic seizures. For more information about Aston Institute of Health and Neurodevelopment (IHN) please visit our website.

Gavin WoodhallDr Stuart Greenhill

Media

Social

Biography

Professor Woodhall researches electrophysiological studies on neurons of the entorhinal cortex (EC) and the hippocampus.

Additional interests include the role of glutamate and GABA receptors in epilepsy in the brain; the role of homeodynamic synaptic scaling in epileptogenesis in the temporal lobe. Autoimmune epilepsies, psychosis and neuronal network dynamics; the relationship between epilepsy and affective disorders. The role of cannabinoids in epilepsy treatment (collaboration with GW Pharma). The role of the primary motor cortex in epilepsy and Parkinson’s disease (in collaboration with Dr. Stuart Greenhill).

The temporal lobe is a brain region which is especially prone to epilepsy. His research focuses on how epilepsy is established, and how dynamic changes in receptor expression and function lead to changes in neuronal network behaviour that may underlie epileptic seizures. Additionally, he is interested in how neuronal network dynamics alter in schizophrenia, and how epilepsy and schizophrenia relate to each other in terms of pathological network function.

Areas of Expertise

Neuronal Network Dynamics
Schizophrenia
Epilepsy
Hippocampus

Education

University of Southampton

PhD

1994

Media Appearances

Aston Institute of Health and Neurodevelopment officially launches new £2.8m MRI scanner

EurekAlert!  online

2022-04-26

After an official ribbon-cutting ceremony hosted by the Institute co-directors Professor Jackie Blissett and Professor Gavin Woodhall, guests were invited to take a tour of the new MRI scanner facilities where imaging researchers were on hand to showcase and discuss their research for which the new MRI scanner is a vital facility.

View More

What causes epilepsy? That is the question - Professor Gavin Woodhall

Epilepsy Sparks Insights  online

2021-08-12

Meet Prof. Gavin Woodhall, a neuropharmacologist, epilepsy researcher, and director for the Institute for Health and Neurodevelopment at Aston University, Birmingham, UK. Or, as Gavin would say “Mostly, I just run a lab!”. Gavin is particularly interested in severe epilepsy syndromes. A key question of his is “What makes a brain develop epilepsy (epileptogenesis)?”

View More

Articles

The AMPA receptor antagonist perampanel suppresses epileptic activity in human focal cortical dysplasia

Epilepsia Open

2022

Focal cortical dysplasia (FCD) is one of the most common malformations causing refractory epilepsy. Dysregulation of glutamatergic systems plays a critical role in the hyperexcitability of dysplastic neurons in FCD lesions. The pharmacoresistant nature of epilepsy associated with FCD may be due to a lack of well-tolerated and precise antiepileptic drugs that can target glutamate receptors. Here, for the first time in human FCD brain slices, we show that the established, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, perampanel has potent antiepileptic action. Moreover, we demonstrate that this effect is due to a reduction in burst firing behavior in human FCD microcircuits. These data support a potential role for the treatment of refractory epilepsy associated with FCD in human patients.

View more

Encephalitis patient-derived monoclonal GABAA receptor antibodies cause epileptic seizures

Journal of Experimental Medicine

2021

Autoantibodies targeting the GABAA receptor (GABAAR) hallmark an autoimmune encephalitis presenting with frequent seizures and psychomotor abnormalities. Their pathogenic role is still not well-defined, given the common overlap with further autoantibodies and the lack of patient-derived mAbs. Five GABAAR mAbs from cerebrospinal fluid cells bound to various epitopes involving the α1 and γ2 receptor subunits, with variable binding strength and partial competition. mAbs selectively reduced GABAergic currents in neuronal cultures without causing receptor internalization. Cerebroventricular infusion of GABAAR mAbs and Fab fragments into rodents induced a severe phenotype with seizures and increased mortality, reminiscent of encephalitis patients’ symptoms. Our results demonstrate direct pathogenicity of autoantibodies on GABAARs independent of Fc-mediated effector functions and provide an animal model for GABAAR encephalitis. They further provide the scientific rationale for clinical treatments using antibody depletion and can serve as tools for the development of antibody-selective immunotherapies.

View more

Multimodal electrophysiological analyses reveal that reduced synaptic excitatory neurotransmission underlies seizures in a model of NMDAR antibody-mediated encephalitis

Communications Biology

2021

Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR antibody) encephalitis, a distinct neuro-immunological disorder in which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization and a state of NMDAR hypofunction. To further understand ictogenesis in this disorder, and to test a potential treatment compound, we developed an NMDAR antibody mediated rat seizure model that displays spontaneous epileptiform activity in vivo and in vitro. Using a combination of electrophysiological and dynamic causal modelling techniques we show that, contrary to expectation, reduction of synaptic excitatory, but not inhibitory, neurotransmission underlies the ictal events through alterations in the dynamical behaviour of microcircuits in brain tissue. Moreover, in vitro application of a neurosteroid, pregnenolone sulphate, that upregulates NMDARs, reduced established ictal activity. This proof-of-concept study highlights the complexity of circuit disturbances that may lead to seizures and the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy.

View more