Significance Statement (115/120 words)Using a chronic anaesthetised preparation, we measured hemodynamic responses evoked by sensory stimulation and respiratory gases in the J20-AD mouse model of Alzheimer's Disease over a period of 3 months. We showed that neurovascular responses were preserved compared to age matched wildtype controls. These results failed to confirm previous investigations reporting a marked reduction of neurovascular coupling in the J20-AD mouse model. However, when our procedure involved acute surgical procedures, previously reported neurovascular deficits were observed. The effects of acute electrode implantation were caused by disturbances to baseline physiology rather than a consequence of the disease condition. These results highlight the importance of experimental procedure when determining the characteristics of animal models of human disease. Abstract (243/250 words)Neurovascular coupling is the process by which neural activity causes localised changes in cerebral blood flow. Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer's disease (AD), and if so, could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime in which evoked hemodynamic responses are comparable to those in awake mice. This protocol was adapted to allow repeated measurements of neurovascular function over three months in the hAPP-J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9-12 months old at the start of the experiment, which is when deficits due to the disease condition would be expected.Mice were chronically prepared with a cranial window through which optical imaging spectroscopy (OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.

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model of ocular inflammation. In the case described, the patient was commenced on topical timolol in order to treat the secondary glaucoma; however, this had no effect on the inflammatory process. It is possible that that oral metoprolol was effective because it had a higher bioavailability within the posterior segment, as well as anteriorly. It was thus effective in suppressing ocular inflammation through the mechanisms described above. References

Outcome prediction of neurological recovery in an unconscious survivor of cardiorespiratory arrest is difficult and uncertain. We describe the case of a 25-yr-old post-arrest survivor who made a remarkable neurological improvement despite a seemingly hopeless prognosis. Conventional clinical and neurophysiological assessments need to be interpreted with care in the presence of uncontrolled seizure activity and sedative medications. The measurement of biochemical markers in the serum and cerebrospinal fluid may be useful in helping the clinician to arrive at a more accurate neurological outcome prediction.