Abstract

Today’s commercial forced exercise platforms had been validated not as a well-designed rehabilitation environment for rats with a stroke, for the reason that rat with a stroke cannot take exercise at a constant intensity for a long period of time. In light of this, this work presented an adaptive, fall-free ischemic stroke rehabilitation mechanism in an animal model, which was implemented in an infrared-sensing adaptive feedback control running wheel (IAFCRW) platform. Consequently, rats with a stroke can be safely rehabilitated all the time, and particularly at full capacity for approximately one third of a training duration, in a completely fall-free environment according to individual physical differences by repeated use of an acceleration/deceleration mechanism. The performance of this platform was assessed using an animal ischemic stroke model. The IAFCRW therapy regimen was validated to outperform a treadmill and a conventional running wheel counterpart with respect to the reduction in the neurobehavioral deficits caused by middle cerebral artery occlusion (MCAo). IAFCRW is the first adaptive forced exercise training platform short of electrical stimulation-assistance in the literature, and ischemic stroke rats benefit more in terms of the behavioral tests run at the end of a 3-week rehabilitation program after a stroke thereby.

Introduction

Medical expense in ischemic stroke patents has long been considered a huge burden to health care companies in many countries, and patients often experience difficulty performing their activities of daily living1,2. Therefore, an effective and completely safe rehabilitation program is seen as crucial to improve patients’ quality of life, and increasing evidence has suggested that physical exercise can enhance the neurological function and motor recovery after stroke3,4,5. In addition, post-ischemic stroke exercise rehabilitation has been proposed as a practical cerebral stroke treatment6,7,8. Rodent, e.g. rat, injury models are frequently employed as a preliminary approach to validating the effectiveness of physical rehabilitation methods5,9,10, and rats are trained at a fixed running speed over a specified time period. These rehabilitation methods have been validated as effective in cerebral stroke prevention11,12, while has been found not to be as effective in cerebral stroke rehabilitation13,14 as in prevention. A reason behind this is that these forced platforms are designed to train normal and healthy rats, but their training parameters could not be directly applied to cerebral stroke rehabilitation programs.
There exist a number of limitations on today’s training platforms, including treadmills and running wheels. Rats are stimulated when they run at the end of treadmill runways, accounting for part of a physiological outcome15. Therefore, treadmill data were very likely to be collected with an interference factor induced by electric shocks. Moreover, electric shock may impose stress on or directly hurt the rats during rehabilitation13,14. Running wheel platforms can be designed as either a voluntary or a motorized form. As its name indicates, rats are permitted to run voluntarily on a voluntary running wheel. However, due to individual differences, this type of running wheel platforms often yields large variations in the final results. To avoid such discrepancies, rats often needed to be selected carefully in advance16,17, and voluntary running wheels were not treated as a key issue. As pointed out in18, rats were afraid of running, held on to the cross bars of a wheel or even stopped running, when trained using commercially available motorized running wheels (MRWs). In addition, commercially available running wheels with a diameter of 35 cm and a width of 12 cm were generally too small for average sized white rats, and were liable to cause rat patient injury19. In addition, it is more difficult to run on a curved runway than on a flat one, and rats often accidentally fell or tumble20,21. Therefore, this study aims to develop and then integrate an adaptive training mechanism into a larger sized running wheel for an improved motor function recovery after stroke.
For the sake of an improved recovery quality, a training mechanism must be made adaptive together with a low level of interference according to the physical conditions of rats during rehabilitation. Previous studies suggested that the stress response to electrical shocks in treadmills resulted in adverse physiological injuries, such as adrenal hypertrophy, splenic atrophy and circulating corticosterone22,23,24. For those taking a rehabilitation program, stress response could be a destructive factor to their recovery13, and is as well an uncontrolled parameter that can affect the final neurological outcomes. Therefore, it is advantageous to remove such potential disadvantages for the sake of clinical research. This study reviewed a number of running wheel platforms that were developed to assist in the effective recovery of rats with an ischemic stroke but short of electric shock. Utilizing an IR sensor-embedded wheel module to detect the running position of a rat, an acceleration/deceleration mechanism was enabled herein in such a way that rats were rehabilitated well in a completely fall-free environment, and adaptively within their capacity for an improved motor function recovery and a reduced cerebral infarct volume.