In the rat VO model, the surgical methods, the permanent nature of the ligation of the common carotid arteries, the lack of exacerbating factors are standard, and therefore the VO model can be regarded as a single defined entity from a technical point of view.As opposed to stroke research, VO studies have the aim of investigation of the longterm effects of chronic cerebral hypoperfusion.In VO rats, the vessel occlusion is permanent and longlasting, reperfusion injury does not occur, the cerebral hypoperfusion is global, and thus a distinct ischemic core and penumbra region cannot be outlined, the damage to the nervous tissue is less dramatic, and there are no obvious signs of motor dysfunction or seizures.In aging and AD, the sequence of the events of cerebral hypoperfusion and neurodegeneration has been a subject of debate.A chronic reduction in CBF was earlier believed to induce the neurodegenerative processes; however, the view was also raised that an earlier neuronal cell loss would require a consequently lower supply of energy substrates, and therefore a lower perfusion rate.Following the introduction of the concept of the neurovascular unit, this controversy can be explained: damage to any of the components of the unit results in consequences to the functioning of the entire unit.With the help of the VO model, the causal and sequential interactions of cerebral hypoperfusion, neuronal injury and memory deficits have been elucidated.Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neural damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system.Because of the vulnerability of the WM, the retina and the visual pathways, the VO model has recently been applied with success in other research fields, such as ischemic WM injury and ischemic eye diseases.In order to tackle the neurological and neuropathological consequences of such a reduction in CBF, a similar condition must be created in experimental animals.VO rats have long been employed to examine the role of cerebral hypoperfusion in neurodegenerative processes.However, the flow pattern in VO rats does not perfectly match that in aging or demented humans.The CBF and cerebral metabolism change dynamically following the onset of VO: the CBF drops sharply immediately after occlusion induction and normalizes over months via compensatory and adaptive mechanisms.There is a relatively long period of time, during which the cerebral hypoperfusion in VO rats is comparable to that in humans.It is first necessary to outline the alterations in CBF and related metabolic rates in VO rats.hand months was recorded in the cortical and WM areas, the CBF in the hippocampus decreasing to a lesser extent. The CBF values had already started to gradually recover at week, but were still significantly lower than the control values weeks after VO induction. Between weeks and months, either only a slight reduction or virtually no reduction has been reported. Finally, after months of VO, the CBF was indistinguishable from the control. Besides the basal flow, the cerebrovascular reactivity was also negatively affected.The CBF responses to challenges with acetazolamide were impaired from min to weeks after VO initiation.