Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

Gómez-Soriano, Julio; Goiriena, E; Taylor, Julian

doi:10.1111/j.1476-5381.2010.00964.x

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…AMPA receptor subunits have been found on spinal α-motoneurons as well as on presynaptic Ia afferents, consistent with their demonstrated role in motor function. It has been shown that the expression of AMPA receptors can affect the clinical signs of spasticity and rigidity following cerebral ischemia; the intrathecal or systemic delivery of the selective AMPA receptor antagonist, NGX424, represents an effective therapy for modulating chronic spasticity in baclofen-tolerant animals (24,25).…”

Section: Discussionmentioning

confidence: 99%

Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression

Tao

Xue

Yang

et al. 2013

International Journal of Molecular Medicine

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Spasticity is one of the most physically debilitating disabilities following stroke and may slow down the potential success of rehabilitation. Glutamate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been shown to play a crucial role in spasticity following cerebral ischemia/reperfusion (I/R) injury. Gua Lou Gui Zhi decoction (GLGZD) is a well-known traditional Chinese formula that has long been used clinically in China to treat muscular spasticity following stroke, epilepsy or spinal cord injury. However, the precise mechanisms behind its neuroprotective and anti-spasticity effects remain poorly understood. In the present study, using a rat model of focal cerebral I/R injury, we evaluated the neuroprotective and anti-spasticity effects of GLGZD and investigated the underlying mechanisms. We found that GLGZD improved neurological deﬁcits and reduced infarct volumes in cerebral I/R-injured rats. In addition, GLGZD reduced cerebral ischemic spasticity since it improved the screen test and Hoffman's reflex (H-reflex) scores. It also reduced glutamate levels in the cerebrospinal fluid and altered the expression of the AMPA receptor subunits. Our data demonstrate that GLGZD exerts neuroprotective and anti-spasticity effects in a cerebral ischemia model via the modulation of glutamate levels and AMPA receptor expression.

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Section: Discussionmentioning

confidence: 99%

Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression

Tao

Xue

Yang

et al. 2013

International Journal of Molecular Medicine

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“…41,[61][62][63] Specifically, the alpha-2 adrenoceptor agonist clonidine has been shown not only to restore inhibition of CR activity after SCI but also to facilitate TA muscle activation during gait, 64 supporting the hypothesis that adequate CR control improves residual motor function. We believe that careful CR testing should be used to benchmark standard and new pharmacological strategies for the control of the SCI spasticity syndrome, 63,65,66 while examining the wider effect of these therapies on residual muscle function after SCI 40,41 Limitations and future studies No correlation was identified between Pl-TA CR activity and the grade of hypertonia or spasm frequency, perhaps reflecting the poor sensitivity of the modified Ashworth and Penn scales to detect flexor reflex activity. Measurement of spasm activity in clinical studies is usually performed with the Penn scale, 35 but this scale often fails to correlate with the underlying pathophysiological mechanisms of SCI spasticity syndrome during movement, 7 or indeed with CR activity in general.…”

Section: Discussionmentioning

confidence: 84%

Abnormal cutaneous flexor reflex activity during controlled isometric plantarflexion in human spinal cord injury spasticity syndrome

et al. 2016

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Study design: Although abnormal cutaneous reflex (CR) activity has been identified during gait after incomplete spinal cord injury (SCI), this activity has not been directly compared in subjects with and without the spasticity syndrome. Objectives: Characterisation of CR activity during controlled rest and 'ramp and hold' phases of controlled plantarflexion in subjects with and without the SCI spasticity syndrome. Design: Transverse descriptive study with non-parametric group analysis. Setting: SCI rehabilitation hospital. Methods: Tibialis Anterior (TA) reflexes were evoked by innocuous cutaneous plantar sole stimulation during rest and ramp and hold phases of plantarflexion torque in non-injured subjects (n = 10) and after SCI with (n = 9) and without (n = 10) hypertonia and/or involuntary spasm activity. Integrated TA reflex responses were analysed as total (50-300 ms) or short (50-200 ms) and long-latency (200-300 ms) activity. Results: Total and long-latency TA activity was inhibited in non-injured subjects and the SCI group without the spasticity syndrome during plantarflexion torque but not in the SCI spasticity group. Furthermore, loss of TA reflex inhibition during plantarflexion correlated with time after SCI (ρ = 0.79, P = 0.009). Moreover, TA reflex activity inversely correlated with maximum plantarflexion torque in the spasticity group (ρ = − 0.75, P = 0.02), despite similar non-reflex TA electromyographic activity during plantarflexion after SCI in subjects with (0.11, 0.08-0.13 mV) or without the spasticity syndrome (0.09, 0.07-0.12 mV). Conclusions: This reflex testing procedure supports previously published evidence for abnormal CR activity after SCI and may characterise the progressive disinhibition of TA reflex activity during controlled plantarflexion in subjects diagnosed with the spasticity syndrome. Spinal Cord (2016) 54, 687-694; doi:10.1038/sc.2016.9; published online 23 February 2016 INTRODUCTION Spasticity was originally defined as an increase in velocity-dependent, tonic stretch reflexes to passive movement 1 and has been used to describe a number of signs and symptoms that together contribute to the syndrome. 2 Cutaneous reflex (CR) dysfunction has also been regarded as an additional sign of the spasticity syndrome following spinal cord injury (SCI), 3-9 especially when detected in subjects with hypertonia and increased tonic stretch reflexes. [10][11][12] In addition, abnormal flexor reflex excitability is present during subacute 4,13 and chronic SCI, 14,15 impacts on residual gait function after SCI 16 and interferes with daily activities. 17 Lower limb CR activity in humans is modulated by several segmental and descending control mechanisms, 18-21 and the loss of descending modulatory mechanisms may contribute to the SCI spasticity syndrome. Tibialis Anterior (TA) muscle reflex activity evoked following cutaneous stimulation of the plantar surface (Pl-TA CR) [22][23][24] has been used as a test to assess the integrity of segmental and descending motor control mechanisms in healthy...

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“…Taken together these symptoms interfere with successful rehabilitation of residual voluntary motor function following incomplete spinal cord injury [ 31 ] and lead to lower quality of life [ 25 , 27 – 32 ]. Due to the multiple spinal pathophysiological mechanisms triggered by SCI, novel treatments should be designed to control neuroinflammation and promote growth of residual descending control systems across the lesion [ 33 – 38 ]. In this context, some symptoms of sensorimotor dysfunction following SCI have been related to glial reactivity at the injury site [ 39 , 40 ], while the restoration of constitutive serotonin and noradrenaline receptors has been reported to be essential for restoring residual motor function [ 41 – 43 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation

et al. 2017

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Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR. Comparison of the expression between healthy rats, SCI rats, and SCI treated with A-HOA rats revealed relevant changes in the expression of genes associated with neuronal morphogenesis and growth, neuronal survival, pain and inflammation. Thus, treatment with A-HOA not only induced a significant overexpression of growth and differentiation factor 10 (GDF10), tenascin C (TNC), aspirin (ASPN) and sushi-repeat-containing X-linked 2 (SRPX2), but also a significant reduction in the expression of prostaglandin E synthase (PTGES) and phospholipases A1 and A2 (PLA1/2). Currently, SCI has very important unmet clinical needs. A-HOA downregulated genes involved with inflammation and upregulated genes involved in neuronal growth, and may serve to promote recovery of function after experimental SCI.

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Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

Cited by 7 publications

References 15 publications

Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression

Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression

Abnormal cutaneous flexor reflex activity during controlled isometric plantarflexion in human spinal cord injury spasticity syndrome

Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation

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