© privat


Alastair M. Buchan, D.Sc.

Professor of Medicine

University of Oxford

John Radcliffe Hospital, Oxford

Born in 1955 in Rinteln, Germany
Studied Natural Sciences at the University of Cambridge, Clinical Medicine at the University of Oxford, Neurology at Harvard University and at the University of Western Ontario, and Cerebral Metabolism at Cornell University Medical Centre, New York


Understanding the Vulnerability of Brain Cells to Ischaemia and Aging

As we live longer lives, it is critically important that we find explanations for the susceptibility of brain cells to injury. We have known for almost 100 years that some cells are much more sensitive to injury than others; it has always been the hope that understanding this selective vulnerability would lead to an understanding of mechanisms of cell death that might be tractable and become targets that would, if the right interventions were deployed, increase the tolerance of brain cells to the aging process.
Critically important to memory and personality is a well-functioning hippocampus. Within the hippocampus, highly connected groups of cells, so-called CA-1 to CA-4, express different vulnerabilities. These cells have been discovered to be the most sensitive cells in the brain; and in particular, those in the CA-1 sector, while being the most highly connected to CA-3, the dentate gyrus and the cortex, are extremely susceptible, whereas CA-3 are the most resistant. Following ischaemia, as a result of aging as a result of epilepsy, the interconnections are easily lost, and my thinking relates to the selective deafferentation and loss of interconnections that might influence cellular vulnerability.
The only thing we can currently do for patients to stop brain cells dying in the face of adversity is by changing temperature (such as cooling); this changes the susceptibility of brain cells, prevents them from dying and allows them to recover following a toxic insult. By changing metabolism and up-regulating mechanisms that utilize high cerebral metabolic rates, we can change the susceptibility of brain cells to ischaemia, and this has implications for the acute treatment of stroke and the prevention of dementia. Techniques that will be engineered to reduce energy demands will, if deployed in acute situations, allow us to protect the brain during stroke injury and help the brain cells to recover during stroke intervention with endogenous neuroprotection. It is hoped that, if we can extrapolate from these observations, we can find ways to sustain cells in more chronic neurodegenerative situations such as in Alzheimer's disease, dementia and neurodegenerative conditions. There is now a need to define specific criteria that will be much more predictive of true reproducibility to avoid unconscious bias, in order to predict what should go forward for effective clinical trials.

Recommended Reading

Attwell, D., A. M. Buchan, S. Charpak, M. Lauritzen, B. MacVicar, and E. Neuman (2010). "Glial and neuronal control of brain blood flow." Nature 468: 233-244.
Papadakis, M., G. Hadley, M. Xilouri, L. C. Hoyte, S. Nagel, G. Tsaknakis, S. M. Watt, C. W. Drakesmith, R. Chen, Z. Zhao, B. Kessler, K. Vekrellis, and A. M. Buchan (2013). "Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy." Nature Medicine 19, 3: 351-357.
Neuhaus, A. A., Y. Couch, G. Hadley, and A. M. Buchan (2017). "Neuroprotection in stroke: the importance of collaboration and reproducibility." Brain 140, 8: 2079-2092.

Publications from the Fellows' Library

Buchan, Alastair M. ( Oxford, 2017)
Neuroprotection in stroke : the importance of collaboration and reproducibility

Buchan, Alastair M. ( London, 2015)
Robust research : institutions must do their part for reproducibility

Buchan, Alastair M. ( London, 2014)
Capillary pericytes regulate cerebral blood flow in health and disease

Buchan, Alastair M. ( Seoul, 2013)
Endogenous neuroprotection : Hamartin modulates an austere approach to staying alive in a recession

Buchan, Alastair M. ( New York, NY, 2012)
Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy

Buchan, Alastair M. ( London, 2010)
Glial and neuronal control of brain blood flow

Evening Colloquium01/15/20

The Brexit Threat to Academic Freedom: What it Means for British and European Academia and How We Should Adapt


Tuesday Colloquium05/26/20