Neuroscience 2

Describe the main events that occur in cerebral ischaemia including energy failure, excitotoxicity, inflammation, and cell death, and the relevant localisation and timescale of these events Understand the transcriptional changes that contribute to endogenous neuroprotective processes and delayed cell death Identify the main molecular targets that could improve outcome but also appreciate the problems encountered in developing treatments

Describe the current main therapeutic options for ischaemic stroke including intravenous and interventional recanalisation therapy Identify additional therapies established for stroke Discuss the evolving options for management of intracerebral haemorrhage

Discuss the advantages and limitations of frequently used animal models of ischaemic and haemorrhagic stroke Address how translational models of stroke can be used to establish new therapeutic avenues focusing on immunomodulatory mechanisms

Identify the key neuropathological features of focal and diffuse TBI Observe the differences between primary and secondary trauma damage List the molecular and cellular pathways implicated in TBI

Describe the basic pathophysiological mechanisms that lead to brain injury following trauma Understand basic principles of CT and MRI imaging Understand how neuroimaging is used to characterise TBI Understand how advanced MRI approaches can be used to study white matter damage

Describe the basics of TBI biomechanics and pathophysiology Critically evaluate the major differences between in vivo and in vitro models Describe the primary mammalian TBI models and discuss their differences Critically evaluate the primary problems of in vivo TBI models Understand why in vivo TBI models are necessary Illustrate the process of preclinical to clinical translation using TBI models

Compare and contrast the clinical presentations of prion disorders with those of the more common neurodegenerative conditions Identify the key neuropathological features of prion diseases Evaluate the prion hypothesis Discuss the factors that led to the emergence of variant Creutzfeldt-Jakob disease

Understand MS epidemiology, incidence, and potential mechanisms accounting for the variability of MS incidence worldwide Describe clinical phenotypes of MS, the disease course, and presenting clinical symptoms Understand imaging features, clinical and laboratory tests, and the key diagnostic criteria, along with potential differential diagnoses Describe the variability of disease course, severity, and clinical and radiological factors affecting prognosis

Describe the main features of the gross and microscopic pathology of MS Understand how the different cellular pathologies might give rise to clinical symptoms Discuss the nature of the inflammatory changes in the MS brain Correlate the various main pathological features with the clinical course of MS

Describe the evidence supporting a role of the immune system in the pathogenesis and clinical course of MS Discuss the interactions between the adaptive and innate immune system in the context of MS pathophysiology Critically evaluate and discuss the relationship between inflammation and neurodegeneration in the context of MS pathogenesis, clinical evolution, and therapeutic needs

Discuss the main categories of treatments for MS Describe the phases of clinical trial development Discuss clinical trial evidence that supports disease modifying treatments for MS Critically evaluate the approved disease modifying treatments and the key aspects of their mechanisms, efficacy, and risks Discuss new treatments in the late stage of clinical development Critically evaluate potential approaches to preventing MS Discuss what a cure for MS should achieve

Give an account of the pattern of inheritance for Huntington's gene carriers, describing the genetic defect and underlying mutation responsible for Huntington's disease Describe the neuropathological changes that occur in the brain of Huntington's disease carriers and the early and later symptoms characteristic of Huntington's disease Discuss the principle brain imaging which can be utilised to assess pathology in the Huntington's disease brain and to monitor changes in brain function following

Describe the clinical features of ALS and the physiological basis for these disease-associated pathologies Describe the neuropathological hallmarks of ALS including the role of TDP-43 positive ubiquitinated protein inclusions and their contribution to other neurodegenerative conditions such as frontotemporal lobar degeneration (FTLD) Assess the importance of identifying mutations in the familial form of ALS (FALS) in understanding the common pathogenic mechanisms underlying familial and sporadic

Identify the key neuropathological features of FTDs Categorise the molecular subtypes of FTD Evaluate the clinicopathological correlations seen in FTDs Research the overlap at the molecular and clinical level between FTD and MND

State the motor and non-motor features of PD Understand and discuss the rational basis for drug treatments of PD and the main complications of treatment Appreciate and discuss the non-medication based aspects of PD management, relating both to the patient, family, carers, and society at large

Identify the key neuropathological features of PD List the stages of pathology progression seen in the brain in PD Discuss how well the post-mortem staging of pathology correlates with motor and non-motor symptoms seem during life Evaluate the 'dual-hit hypothesis' of an environmental trigger for PD

Critically evaluate the processes involved in development and normal survival and maintenance of dopaminergic neurons, including transcriptional regulation of neuronal development and survival and mitochondrial energy metabolism Critically evaluate the molecular mechanisms that may contribute to the vulnerability of midbrain dopaminergic neurons, including oxidative balance and stress, synaptic function, and protein handling

Name the principle gene mutations associated with the familial forms of Parkinson's disease and describe the cellular functions of the proteins which these genes encode for Describe the neurodegenerative pathways associated with these mutated proteins and discuss whether neurodegeneration pathways for the familial and sporadic forms of PD overlap Discuss how genome-wide association studies have identified risk genes for the development of idiopathic PD and how they have been used to identify key

Define the term parkinsonism and list the CNS disorders which may present in this way Identify the key neuropathological features of progressive supranuclear palsy (PSP) Identify the key neuropathological features of multiple system atrophy (MSA) Identify the key neuropathological features of corticobasal degeneration (CBD) Research how Parkinson's plus disorders can be distinguished clinically while the patient is alive

Describe the typical clinical presentation of AD, contrasting it with other common causes of cognitive impairment and dementia Be aware of atypical presentations and how they relate to different patterns of brain atrophy Discuss the different factors thought to influence the development of clinical AD, including genetics and predisposing factors, as well as evaluating other influences such as trauma, diet, and educational attainment Discuss the main current treatments for AD and their limitation

Identify the key neuropathological features of AD Compare and contrast the cholinergic and amyloid cascade hypotheses Evaluate the methods being developed to assess brain pathology and to confirm the diagnosis of AD in living patients Discuss the utility of post-mortem examination as an end point in clinical trials

Describe the molecular mechanisms which cause Alzheimer's-type pathology Discuss the potential risk factors for the development of AD Identify the current therapeutic approaches being researched to treat AD and their molecular targets Criticallt evaluate the various types of in vivo and in vitro experimental approached being utilised in AD research

Describe the commonly used imaging techniques available to assist in the diagnosis of AD and PD Discuss the novel molecular imaging techniques being used in AD, and how these will be useful in patient management and therapeutic interventions Critically evaluate how these imaging techniques will change the classification and diagnosis of AD

Give a clinical definition of dementia Discuss the most common forms of dementia and their typical features of presentation Describe the pathway from presentation to examination, investigation, and treatment Appreciate the broad spectrum of pathological disturbances that can result in a clinical syndrome of dementia

Discuss the principle gene therapy using lentiviruses to treat neurodegenerative diseases in a symptomatic or disease-modifying manner

Understand the definitions of epilepsy and seizures and the difference between the two Understand the basic epidemiology of epilepsy Understand the principles of the different anti-epileptic drugs' mechanisms of action Give examples of different drugs that exploit these different mechanisms