Ace Therapeutics provides reliable NHP models of stroke, including ET-1 induced MCAO model in NHPs, cynomolgus MCAO model, and rhesus monkeys endovascular stroke model. These models allow us to assess hand motor function and recovery after stroke.

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• Behavioral Assessment of Motor in Animal Models of Stroke

Hand Motor Impairment After Stroke

Stroke has a significant impact on the activities of daily living of stroke patients. Fine motor impairments are particularly common, reducing movement and coordination in stroke patients and contributing significantly to subsequent disability.

Weakness or paresis, especially in voluntary movements, is a primary symptom of stroke due to damage to the descending motor pathways. Initially, the affected upper limb is flaccid but develops an increased tone characterized by a flexor synergy pattern. This tone abnormality manifests as heightened resting tone, exaggerated stretch reflexes, and varying degrees of spasticity. Motor execution issues post-stroke are often linked to disturbed control of α-γ motor neuron activity, resulting in synergistic movements rather than isolated ones. The Fugl-Meyer Motor Assessment Scale is commonly used to evaluate motor impairment, focusing on synergistic versus isolated movement patterns. However, it does not adequately assess specific hand motor impairments, such as difficulties with grasping or applying the right fingertip forces, which may require different treatment approaches.

Advantages of Non-Human Primate (NHP) Models of Stroke

Animal models, particularly NHPs, are used to study the effects of cerebral ischemia on motor function in stroke research. While there are similarities between human and animal neurological systems, differences limit the direct translation of findings. NHPs share closer similarities in motor systems and fine motor control with humans, making them valuable for studying ischemic strokes. The endovascular transient middle cerebral artery occlusion (MCAO) method is commonly used to induce strokes in NHPs. Contralateral motor deficits in manual dexterity and grip strength have been observed in these models. For example, African green monkeys exhibited impaired dexterity in object retrieval tasks, while rhesus monkeys showed recovery of hand dexterity to baseline levels after cortical injury. Despite their complexity, NHP stroke models provide important insights into human ischemic stroke.

The Hand Dexterity Task (HDT) in NHP Models of Stroke

HDT is used to assess the fine motor function of the hand and fingers. Monkeys are typically tested for hand fine motor function using a test device that controls, quantifies, and video-records the responses of each hand. Using this device, monkeys are trained in HDT for a total of 15 days (Mondays, Wednesdays, and Fridays for a total of 5 weeks.) The HDT required monkeys to accurately control the juxtaposition of their fingers, specifically the thumb and index finger, to remove small, visible food rewards from two different sized circular holes in a Plexiglas tray.

When the monkey's hand enter the apparatus, a photocell activated a timer to record the time it took to remove the food. The experimenter records whether the reward is successfully retrieved or not, and the response (retrieval time) is recorded. Each test day consisted of 32 trials (16 trials for each hole size and hand), performed in a pseudo-randomized order to prevent bias. Monkeys are given 30 seconds to complete each trial and are offered a second chance if they fail the first time. If unsuccessful after two attempts, a non-response was recorded.

Fig.1. A photograph of the plexiglass testing apparatus used to administer the HDT. (Moore, et al., 2016)

Determine Hand Dominance Using the HDT

After completing pre-training on the HDT, monkeys undergo free-choice trials where both sides of the apparatus are baited to identify their preferred hand. This preference is then compared to pre-operative acquisition rates for each hand. The cortical injury is intentionally targeted to the hemisphere that controls the preferred hand, ensuring that monkeys are motivated to use the impaired hand during post-operative testing.

The Object Retrieval Task With a Barrier-Detour in NHP Models of Stroke

The object retrieval task with a barrier detour can be used to assess upper limb motor deficits in monkeys after experimental ischemic stroke. The task involves monkeys retrieving a reward (fruit) from the open side (around an obstacle) of a transparent box fixed on a tray. The orientation of the box opening is changed during the test. Behavioral tests are conducted over 8 days, with all tests taking place 23 hours after the animals' last meal. Experimenters record three main parameters for each trial: (1) the animal's ability to reach the front, left, or right side of the box, (2) the hand chosen for reaching, left or right, and (3) the outcome of reaching, success or failure.

Fig.2. Impaired dexterity in the contralateral arm. (McEntire, et al., 2016)

1. Moore, T. L., et al. (2016). Inosine enhances recovery of grasp following cortical injury to the primary motor cortex of the rhesus monkey. Restorative neurology and neuroscience, 34(5), 827-848.
2. McEntire, C. R., et al. (2016). Impaired arm function and finger dexterity in a nonhuman primate model of stroke: motor and cognitive assessments. Stroke, 47(4), 1109-1116.