Journal of Animal Research & Veterinary Science Category: Agriculture Type: Review Article
Effects of Stroke on Motor Function in Laboratory Animals
- Jordan Bourbo1*
- 1 Animal Science Major In The College Of Agriculture And Environmental Science, University Of Georgia, Athens, GA, United States
*Corresponding Author:Jordan Bourbo
Animal Science Major In The College Of Agriculture And Environmental Science, University Of Georgia, Athens, GA, United States
Received Date: Jan 25, 2019 Accepted Date: Feb 06, 2019 Published Date: Feb 20, 2019
Stroke is the fourth leading cause of death in the United States , and there are currently only two treatments that are approved by the Food and Drug Administration in emergency management-thrombectomy and tissue plasminogen activator . However, these treatments are very difficult to administer because they have to be given within hours post stroke. These treatments have limited restorative effects which can lead to the development of motor function impairments .
RODENT MOTOR FUNCTION ASSESSMENT
Following a stroke that affects upper or lower extremity function, humans tend to develop a reliance on their less-affected limb . Therefore, researchers fear that the learned non-use of the affected limb post stroke can impede potential recovery . An example of this is shown through the results from the cylinder test. Roome, et al., found that when stroke-induced rats are placed in the cylinder, they rely more heavily on their unaffected forelimb paw for support, therefore resulting in fewer touches with the affected paw . Similar results were observed with the ledged tapered beam test. In this test, animals must walk across an elevated beam that tapers at one end. Any type of misstep on the beam is viewed as deficits in hindlimb function . Tahamtan M, et al., has showed that the number of missteps increases on the affected hindlimb post stroke and become more reliant on the unaffected hindlimb . The grid walking test has also been utilized to determine if rodents develop a heavier reliance on their less affected limb after stroke. The grid walking test has been found to objectively demonstrate motor coordination deficits and rehabilitation effects after stroke . The animal is placed on grid that is elevated with a small opening. An intact animal can do the test without any fault , however, animals post-stroke make a significant amount of missteps throughout the test . Different tests and studies are being conducted to determine the correlations between forelimb, hindlimb, and gait assessment throughout rodent models . Additional studies and trials are needed to be done in different animals to adequality assess and conclude a potential therapy treatment in humans, not just rodents.
SWINE MOTOR FUNCTION
For gait analysis, the pigs are trained to walk through a semi-circular track and are recorded with high speed cameras to determine changes in gait parameters. Gait analysis in a healthy pig demonstrates symmetry in hindlimb and forelimb swing and stance times, step length, step velocity, and maximum hoof height. A study conducted by Duberstein, et al., recorded gait post stroke in swine. His results exhibited lower maximum front hoof height on the affected stroke side, as well as shorter swing time and longer stance time on the affected hindlimb. This suggests that gait analysis is a highly sensitive detection method for changes in gait parameters in swine . Webb, et al., further demonstrated this through his study that tested gait in untreated post stroke swine, and neural stem cell treated swine post stroke. After 28 days post stroke, the treated pigs exhibited a significant increase in temporal and spatial gait parameters in comparison to untreated pigs. In treated swine, there were improvements in velocity, cadence, and swing percent of cycle .
In open field testing, a pig is put in a fenced in area for a certain amount of time and observed . Tracking software is used to analyze the movement of the pigs throughout the time spent in the open field area and measures changes in motor activity, such as distance travelled . Pre-stroke pigs exhibited high mobility and thus traveled more distance compared to stroke pigs. Stroke pigs travelled significantly less distance the first week post stroke which indicates that mobility may have been impaired. However, after seven days post stroke, pigs treated with neural stem cells recovered while control pigs were still significantly impaired . Only a few studies have been done analyzing changes in motor function post stroke in swine. Therefore, more studies need to be conducted to determine the changes in motor functions in swine after strokes.
A study was conducted by Ding, et al., to determine if complex motor training on Rota-rod can aid motor function improvement as compared to simple locomotors exercise on a treadmill. The Rota-rod performance test is a performance test based on a rotating rod with forced motor activity being applied . The test evaluates balance, grip strength, and motor coordination of the rodents. Motor function was evaluated by a testing foot fault placing, parallel bar crossing, rope and ladder climbing before and at 14 or 28 days after training procedures in both ischemic and normal rodents. Compared with both treadmill exercised and non-trained animals, Rota-rod-trained animals with or without a stroke significantly improved motor performance of all tasks except for foot fault placing after 14 days of training, with normal rats having better performance . A similar study found the same results after testing adult male rats post stroke with treadmill training, motor training on the Rota-rod, or both Rota-rod and treadmill training.
Through different assessments such as limb placement, Seo HG, et al., was able to conclude that Rota-rod training showed more improvement in motor function and coordination than tredmill training . The implications of Rota-rod training in humans and also treadmill training has been found to have the possibility to help keep the remaining cortical tissue in the brain intact, therefore improving motor function .
- Hu J, Huang S, Zhu L, Huang W, Zhao Y, et al. (2018) Tissue plasminogen activator-porous magnetic microrods for targeted thrombolytic therapy after ischemic stroke. ACS Appl Mater Interfaces 10: 32988-32997.
- Mair G, Wardlaw JM (2014) Imaging of acute stroke prior to treatment: Current practice and evolving techniques. Br J Radiol 87: 20140216.
- Kerr AL, Tennant KA (2014) Compensatory limb use and behavioral assessment of motor skill learning following sensorimotor cortex injury in a mouse model of ischemic stroke. J Vis Exp, Pg no: 1.
- Yamori Y, Horie R, Handa H, Sato M, Fukase M (1976) Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans. Stroke 7: 46-53.
- Lind NM, Moustgaard A, Jelsing J, Vajta G, Cumming P, et al. (2007) The use of pigs in neuroscience: Modeling brain disorders. Neurosci Biobehav Rev 31: 728-751.
- Yan T, Chopp M, Chen J (2015) Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke. Neurosci Bull 31: 717-734.
- O'Collins VE, Macleod MR, Cox SF, Raay LV, Aleksoska E, et al. (2011) Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing. J Cereb Blood Flow Metab 31: 962-975.
- O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, et al. (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59: 467-477.
- Schaar KL, Brenneman MM, Savitz SI (2010) Functional assessments in the rodent stroke model. Exp Transl Stroke Med 2: 13.
- Whishaw IQ, Kolb B (2005) The behavior of the laboratory rat : A handbook with tests. Oxford University Press, Oxford, UK.
- Taub E, Uswatte G, Mark VW, Morris DM (2006) The learned nonuse phenomenon: Implications for rehabilitation. Eura Medicophys 42: 241-256.
- Allred RP, Maldonado MA, Hsu And JE, Jones TA (2005) Training the “less-affected” forelimb after unilateral cortical infarcts interferes with functional recovery of the impaired forelimb in rats. Restor Neurol Neurosci 23: 297-302.
- Roome RB, Vanderluit JL (2015) Paw-dragging: A novel, sensitive analysis of the mouse cylinder test. J Vis Exp, Pg no: 52701.
- Bland ST, Schallert T, Strong R, Aronowski J, Grotta JC, et al. (2000) Early exclusive use of the affected forelimb after moderate transient focal ischemia in rats: Functional and anatomic outcome. Stroke 31: 1144-1152.
- Tahamtan M, Allahtavakoli M, Abbasnejad M, Roohbakhsh A, Taghipour Z, et al. (2013) Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats. Arch Iran Med 16: 697-704.
- Chao OY, Pum ME, Li JS, Huston JP (2012) The grid-walking test: Assessment of sensorimotor deficits after moderate or severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and medial forebrain bundle. Neuroscience 202: 318-325.
- Whishaw IQ, Coles BL (1996) Varieties of paw and digit movement during spontaneous food handling in rats: Postures, bimanual coordination, preferences, and the effect of forelimb cortex lesions. Behav Brain Res 77: 135-148.
- Baker EW, Platt SR, Lau VW, Grace HE, Holmes SP, et al. (2017) Induced pluripotent stem cell-derived neural stem cell therapy enhances recovery in an ischemic stroke pig model. Sci Rep 7: 10075.
- Platt SR, Holmes SP, Howerth EW, Duberstein KJJ, Dove CR, et al. (2014) Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. Exp Transl Stroke Med 6: 5.
- Sommer CJ (2017) Ischemic stroke: Experimental models and reality. Acta Neuropathol 133: 245-261.
- Webb RL, Kaiser EE, Jurgielewicz BJ, Spellicy S, Scoville SL, et al. (2018) Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke 49: 1248-1256.
- Duberstein KJ, Platt SR, Holmes SP, Dove CR, Howerth EW, et al. (2014) Gait analysis in a pre- and post-ischemic stroke biomedical pig model. Physiol Behav 125: 8-16.
- Castel D, Sabbag I, Nasaev E, Peng S, Meilin S (2018) Open field and a behavior score in PNT model for neuropathic pain in pigs. J Pain Res 11: 2279-2293.
- Wang T, Yu DR, Huang J, Liu Q, Wang DX, et al. (2018) Multimodal rehabilitation program promotes motor function recovery of rats after ischemic stroke by upregulating expressions of GAP-43, SYN, HSP70, and C-MYC. J Stroke Cerebrovasc Dis 27: 2829-2839.
- Yagura H, Miyai I, Seike Y, Suzuki T, Yanagihara T (2003) Benefit of inpatient multidisciplinary rehabilitation up to 1 year after stroke. Arch Phys Med Rehabil 84: 1687-1691.
- Deacon RM (2013) Measuring motor coordination in mice. J Vis Exp, Pg no: 2609.
- Ding Y, Li J, Lai Q, Rafols JA, Luan X, et al. (2004) Motor balance and coordination training enhances functional outcome in rat with transient middle cerebral artery occlusion. Neuroscience 123: 667-674.
- Seo HG, Kim DY, Park HW, Lee SU, Park SH (2010) Early motor balance and coordination training increased synaptophysin in subcortical regions of the ischemic rat brain. J Korean Med Sci 25: 1638-1645.
- Jones EG, Pons TP (1998) Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. Science 282: 1121-1125.
Citation:Bourbo J (2019) Effects of Stroke on Motor Function in Laboratory Animals. J Anim Res Vet Sci 3: 013.
Copyright: © 2019 Jordan Bourbo, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.