The Effects of Repeated Rehabilitation “Tune-Ups” on Functional Recovery After Focal Ischemia in Rats

Clarke, Jared; Malá, Hana; Windle, Victoria; Chernenko, Garry; Corbett, Dale

doi:10.1177/1545968309341067

Cited by 22 publications

(19 citation statements)

References 62 publications

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“…In accordance with earlier studies, 5,22 ET-1 applied to the forelimb motor cortex and dorsolateral striatum produced profound impairments in sensorimotor function as demonstrated with the NDS assessments (Figure 1). Although the NDS was used to confirm ischemic injury and persisting sensorimotor deficits over the short time course of this study, these assessments are generally not sensitive to detecting rehabilitative changes in the long term because of the robust spontaneous recovery as observed in the current study.…”

Section: Discussionsupporting

confidence: 91%

Early Poststroke Experience Differentially Alters Periinfarct Layer II and III Cortex

Clarke

Langdon

Corbett

2014

J Cereb Blood Flow Metab

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Early poststroke rehabilitation effectively improves recovery of function, likely by engaging multiple plasticity processes through use-dependent activation of neural circuits. The loci of such neuroplastic reorganization have not been examined during the initial phase of behavioral recovery. In the current study, we sought to evaluate sub-components of rehabilitation and to identify brain sites first engaged by early rehabilitation. Rats were subjected to endothelin-1 ischemia and placed in either enriched environment (EE), daily reach training (RT), combination of enriched environment and reach training (ER), or standard housing (ST) starting 7 days post ischemia. Functional and histopathological assessments were made after 2, 5, and 10 days of treatment. Animals exposed to 10 days of ER treatment exhibited significantly more use-dependent neuronal activity (FosB/DFosB expression) in perilesional cortex than those exposed to EE, RT, or ST treatments. Similar trends were observed in both perilesional striatum and contralesional forelimb motor cortex. This use-dependent plasticity was not explained by differences in neuronal death, inflammation, or lesion volume. The increased activity likely contributes to the neuroplastic changes and functional recovery observed after extended periods of rehabilitation. Importantly, EE or RT alone did not lead to enhanced activity suggesting that combination therapy is necessary to promote maximum recovery.

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Section: Discussionsupporting

confidence: 91%

Early Poststroke Experience Differentially Alters Periinfarct Layer II and III Cortex

Clarke

Langdon

Corbett

2014

J Cereb Blood Flow Metab

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“…Baseline performance was obtained prior to the surgery and the animals were assessed again after the surgery. The average number of slips over three trials was calculated at each time point and used for statistical analyses (Clarke et al 2009, Langdon et al 2011.…”

Section: Behavioral Assessmentsmentioning

confidence: 99%

Maternal high-fat diet influences stroke outcome in adult rat offspring

Lin

Shao

Zhou

et al. 2015

Journal of Molecular Endocrinology

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Diet-induced epigenetic modifications in early life could contribute to later health problem. However, it remains to be established whether high-fat diet (HFD) consumption during pregnancy and the suckling period could predispose the offspring to stroke. The present study investigated the influence of maternal HFD on stroke outcome in adult offspring. Female Sprague-Dawley rats were fed a normal diet (5.3% fat) or a HFD (25.7% fat), just before pregnancy until the end of lactation. Male offspring were fed with the control diet or the HFD after weaning, to form four groups (control offspring fed with the control diet (C/C) or the HFD (C/HFD) and offspring of fat-fed dams fed with the control diet (HFD/C) or the HFD (HFD/HFD)). The offspring received middle cerebral artery occlusion on day 120 followed by behavioral tests (neurological deficit score, staircase-reaching test and beam-traversing test), and infarct volumes were also calculated. We found that the HFD/C rats displayed larger infarct volume and aggravated functional deficits (all P!0.05), compared with the C/C rats, indicating that maternal fat-rich diet renders the brain more susceptible to the consequences of ischemic injury. Moreover, maternal HFD offspring displayed elevated glucocorticoid concentrations following stroke, and increased glucocorticoid receptor expression. In addition, adrenalectomy reversed the effects of maternal HFD on stroke outcome when corticosterone was replaced at baseline, but not ischemic, concentrations. Furthermore, expression of brain-derived neurotrophic factor (BDNF) in the ipsilateral hippocampus was decreased in the HFD/C offspring (P!0.05), compared with the C/C offspring. Taken together, maternal diet can substantially influence adult cerebrovascular health, through the programming of central BDNF expression and the hypothalamic-pituitary-adrenal axis.

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“…Motor impairments are among the most common and chronic consequences of stroke 25,26 , and are therefore the focus of a number of basic science research laboratories (e.g., [27][28][29][30][31][32] ). Skilled reaching tasks are the most commonly used tests of dexterous forelimb use in rodents, and have historically been most often used in rat models of injury (e.g., 11,19,28,33 ), although their use in mouse models is becoming quite frequent 34,35 .…”

Section: Discussionmentioning

confidence: 99%

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Kerr

Tennant

2014

JoVE

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Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models. Video LinkThe video component of this article can be found at

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The Effects of Repeated Rehabilitation “Tune-Ups” on Functional Recovery After Focal Ischemia in Rats

Cited by 22 publications

References 62 publications

Early Poststroke Experience Differentially Alters Periinfarct Layer II and III Cortex

Early Poststroke Experience Differentially Alters Periinfarct Layer II and III Cortex

Maternal high-fat diet influences stroke outcome in adult rat offspring

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

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