Effect of the Noncompetitive NMDA Antagonists MK-801 and Ketamine on the &lt;i&gt;Spastic&lt;/i&gt; Han-Wistar Mutant: A Rat Model of Excitotoxicity

Brunson, Kristen L.; Khanna, Aparna; Cromwell, Howard C.; Cohen, Rochelle S.

doi:10.1159/000048694

Cited by 24 publications

(16 citation statements)

References 53 publications

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“…Previously, this mutant rat model has been used for neural studies exclusively (7,39,44). The mechanical properties of the spastic rat calf muscles found in the present study are consistent with the reduced functional range of motion and increased stiffness reported clinically in human limbs affected by spasticity (17,31,32,40), and the narrower active lengthforce curves estimated in in vivo studies on human GA (2,15,16).…”

Section: Discussionsupporting

confidence: 90%

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Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat

Olesen

Jensen

Uhlendorf

et al. 2014

Journal of Applied Physiology

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Olesen AT, Jensen BR, Uhlendorf TL, Cohen RW, Baan GC, Maas H. Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat. J Appl Physiol 117: 989-997, 2014. First published September 4, 2014 doi:10.1152/japplphysiol.00587.2014.-The purpose of the present study was to investigate muscle mechanical properties and mechanical interaction between muscles in the lower hindlimb of the spastic mutant rat. Length-force characteristics of gastrocnemius (GA), soleus (SO), and plantaris (PL) were assessed in anesthetized spastic and normally developed Han-Wistar rats. In addition, the extent of epimuscular myofascial force transmission between synergistic GA, SO, and PL, as well as between the calf muscles and antagonistic tibialis anterior (TA), was investigated. Active length-force curves of spastic GA and PL were narrower with a reduced maximal active force. In contrast, active length-force characteristics of spastic SO were similar to those of controls. In reference position (90°ankle and knee angle), higher resistance to ankle dorsiflexion and increased passive stiffness was found for the spastic calf muscle group. At optimum length, passive stiffness and passive force of spastic GA were decreased, whereas those of spastic SO were increased. No mechanical interaction between the calf muscles and TA was found. As GA was lengthened, force from SO and PL declined despite a constant muscle-tendon unit length of SO and PL. However, the extent of this interaction was not different in spastic rats. In conclusion, the effects of spasticity on length-force characteristics were muscle specific. The changes observed for GA and PL muscles are consistent with the changes in limb mechanics reported for human patients. Our results indicate that altered mechanics in spastic rats cannot be attributed to differences in mechanical interaction, but originate from individual muscular structures. muscle spasticity; mechanical properties; myofascial force transmission; muscle stiffness MUSCLE SPASTICITY HAS BEEN defined as a "velocity-depended resistance to stretch" (24) and arises secondary to upper motoneuron lesions with cerebral palsy and stroke as the most common examples (12). Individuals suffering from spasticity typically experience muscle weakness, enhanced joint stiffness, increased muscle tone, reduced range of joint motion, increased antagonistic co-contraction, and exaggerated reflexes (1,3,6,12,13,32,41,48). These effects severely impair the ability to perform daily activities, and treatment is often needed.To asses whether some of these symptoms are related to altered mechanical properties of muscle-tendon units (MTUs), passive and active length-force characteristics have been estimated as joint moment as a function of gastrocnemius (GA) fascicle length. Spastic GA was found to be stiffer than normally developed in such studies (2, 3). The active lengthforce curve of the spastic GA was narrower and the optimum length was shifted to a shorter fascicle length than in normally deve...

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Section: Discussionsupporting

confidence: 90%

“…At 42-50 days postnatal, spastic paresis is manifested by limb rigidity and more plantar-flexed paws (37), which is also typical in humans with spastic lower legs. The spastic mutant rat has previously been used for neurophysiological studies (7,8,39,44), but the mechanical properties of its skeletal muscles have never been investigated.…”

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confidence: 99%

Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat

Olesen

Jensen

Uhlendorf

et al. 2014

Journal of Applied Physiology

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“…Some studies (145)(146)(147), though not all (148,149), suggest that NMDA antagonists trigger presynaptic release of glutamate, which, in turn, binds to AMPA receptors. No matter what the underlying mechanism, the apparent linkage between NMDA antagonism and AMPA receptor activation may help clarify how ketamine can be neuroprotective (150,151) in some contexts but potentially neurotoxic (151)(152)(153) in others. The necessity of AMPA activation implies that ketamine induces synaptogenesis by increasing glutamate signaling rather than by protecting neurons from glutamate excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Newport¹,

Carpenter²,

McDonald³

et al. 2015

AJP

501

377

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The antidepressant efficacy of ketamine, and perhaps D-cycloserine and rapastinel, holds promise for future glutamate-modulating strategies; however, the ineffectiveness of other NMDA antagonists suggests that any forthcoming advances will depend on improving our understanding of ketamine's mechanism of action. The fleeting nature of ketamine's therapeutic benefit, coupled with its potential for abuse and neurotoxicity, suggest that its use in the clinical setting warrants caution.

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“…In a study done by Brunson et al (2001), it was demonstrated that ketamine has a neuroprotective effect in the hippocampus and cerebellum of a mutant strain of rat. On the contrary, in a study performed by Rudin et al (2005), a single dose ketamine administration to 7-dayold mice (neonatal) was shown to induce apoptosis in both the sensorimotor cortex and cerebellum.…”

Section: Introductionmentioning

confidence: 99%

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

Chan

Fan

et al. 2011

Microscopy Res & Technique

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To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg(-1) intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co-administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two-way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum.

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Effect of the Noncompetitive NMDA Antagonists MK-801 and Ketamine on the <i>Spastic</i> Han-Wistar Mutant: A Rat Model of Excitotoxicity

Cited by 24 publications

References 53 publications

Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat

Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

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