Animal models of post-ischemic forced use rehabilitation: methods, considerations, and limitations

Abstract

Many survivors of stroke experience arm impairments, which can severely impact their quality of life. Forcing use of the impaired arm appears to improve functional recovery in post-stroke hemiplegic patients, however the mechanisms underlying improved recovery remain unclear. Animal models of post-stroke rehabilitation could prove critical to investigating such mechanisms, however modeling forced use in animals has proven challenging. Potential problems associated with reported experimental models include variability between stroke methods, rehabilitation paradigms, and reported outcome measures. Herein, we provide an overview of commonly used stroke models, including advantages and disadvantages of each with respect to studying rehabilitation. We then review various forced use rehabilitation paradigms, and highlight potential difficulties and translational problems. Lastly, we discuss the variety of functional outcome measures described by experimental researchers. To conclude, we outline ongoing challenges faced by researchers, and the importance of translational communication. Many stroke patients rely critically on rehabilitation of post-stroke impairments, and continued effort toward progression of rehabilitative techniques is warranted to ensure best possible treatment of the devastating effects of stroke.

Direct reprogramming of astrocytes to neurons leads to functional recovery after stroke

“…The endothelin-1 model of cortical injury produced reproducible lesions with small but significant motor deficits that were detectable using gait analysis until PSD 63 (the longest time examined), and lesion volumes similar to those reported previously [26,27]. Endohelin-1 is a commonly used preclinical model of ischemic stroke as it mimics the pathophysiological processes that are more closely related to the clinical condition, including excitotoxicity, generation of reactive oxygen species, related inflammatory responses, and gliosis [28,29]. Importantly, this model results in functional impairments can be recovered, which is critical for exploring the efficacy of cell therapy/regenerative interventions for stroke recovery.…”

Ischemic lesions localized to the medial prefrontal cortex produce selective deficits in measures of executive function in rats

“…Other commonly used models such as 2-and 4-vessel occlusion and hypoxia-ischemia are similarly compromised in that the lesions are typically localized to specific regions, notably the CA1 region of the hippocampus, and photothrombotic models are largely restricted to surface vasculature [16,17]. Recently, we have described how small well-localized ischemic lesions produced by surgical microinjection of endothelin-1 (ET-1) have been used successfully to produce discreet functional deficits in rats [18][19][20]. Endothelin-1 is a potent vasoconstrictor capable of temporarily occluding blood vessels via an action on endothelin receptors [21].…”

Criteria for assessing peripheral nerve injury. Behavioral and functional assessment in non-operated Wistar rats

“…In this context, several functional tests were developed to better study and understand the limiting factors in experimental studies. There are several functional tests described in the literature for the evaluation of different nerves or groups of nerves [9][10][11][12][13][14][15][16][17][18][19] . These tests do not evaluate reflex acts, but complex motor acts involving agonist and antagonist muscles 11,13,16 .…”