Table 1 Features of VCI, as related to experimental models considered
From: Translational models for vascular cognitive impairment: a review including larger species
| Â | MCAo Rats, mice | MCAo Sheep | Chronic hypo-perfusion Rats, mice | Chronic hypo-perfusion Baboons | HHCy Rats, mice | Chronic HT: SHRSP | Chronic HT: monkeys | Aged dogs | CADASIL mice |
|---|---|---|---|---|---|---|---|---|---|
Cognitive changes: executive function, attention, processing speed, apathy/reward seeking, memory decline | deficits in spatial and recognition memory; passive avoidance. | post-stroke apathy; higher cognitive function NR | Working memory and reference memory deficits | NR | Impaired spatial learning, working memory | Spatial memory impaired | Reduced executive function, attention, short-term memory | Executive function, spatial learning and memory; visuo-spatial function, simple associative learning; open field activity, anxiety, dis-orientation; restlessness | NR |
Sub-cortical motor symptoms: Impaired gait, balance, posture | Sensori-motor deficits. Severity depends on lesion size. | Sensori-motor deficits reflecting lesion size and location | motor deficits on rotarod (GCAS mice). | NR | NA | Sensori-motor deficits. Severity depends on lesion type, location, size | NA | NR | Motor deficits in some aged animals |
No motor deficits reported for BCAS | |||||||||
Risk factors: age, hypertension, DM, obesity | some studies: age, HT, obesity | NR | HT (SHRSP) | NA | HHCy | HT, dietary risk factors (high fat, high salt); hypo-perfusion | HT | Age (obesity?) | Notch3 mutation |
Co-morbidities e.g., mutant APP | |||||||||
Brain gross pathology: atrophy, large infarcts.. | Focal ischaemic lesion; cortical and striatal | Focal ischaemic lesion; atrophy and pseudo-cyst in chronic stage | NA | NA | NA | Ischaemic lesions and He; variable extent, location | NA | Ventricles enlarged; brain atrophy; spontaneous lesions | NR |
Brain neuropathology: Lacunes/micro-Hge, micro-bleeds, diffuse WML | Rapid cell death in ischaemic core. Leukocyte infiltration, neuro-inflammatory changes. Delayed damage in remote areas. | acute cell death in core; inflammatory response; lepto-meningeal and vascular re-organisation; delayed neuroinflammatory response in remote areas | Diffuse WML; micro-Hge; Impaired BBB; microglial activation; | Diffuse WML; microglial activation; Impaired BBB | Micro-Hge in some models | BBB changes, neuro-inflammation. | Focal micro-infarcts; No diffuse WML | Aβ plaques, hippocampal neuronal loss, gliosis, micro-Hge | WML - vacuolisation; focal lesions in some aged animals |
Diffuse WML in animals with UCCAo | |||||||||
Small vessel changes: Arteriolosclerosis, BBB dysfunction, CAA | NA | NR | CAA in some models | NA | CAA, micro-vascular rarefaction; BBB dysfunction in some models | BBB dysfunction (some studies) | Increased tortuosity | CAA. BBB dysfunction (on MRI) | GOM deposits, impaired CVR; BBB dysfunction (some studies) |