scholarly journals Hindlimb motor responses to unilateral brain injury: spinal cord encoding and left-right asymmetry

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mengliang Zhang ◽  
Hiroyuki Watanabe ◽  
Daniil Sarkisyan ◽  
Marlene Storm Andersen ◽  
Olga Nosova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Injury ◽  
Brain Lesion ◽  
Motor Deficits ◽  
Postural Asymmetry ◽  
The Asymmetry ◽  
Withdrawal Reflexes ◽  
The Right ◽  
Lumbar Spinal ◽  
Unilateral Brain

Abstract Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a unilateral lesion to the cerebellum produced postural asymmetry with ipsilateral hindlimb flexion that was retained after complete spinal cord transection. Here we demonstrate that hindlimb postural asymmetry in rats is induced by a unilateral injury of the hindlimb sensorimotor cortex, and characterize this phenomenon as a model of spinal neuroplasticity underlying asymmetric motor deficits. After cortical lesion, the asymmetry was developed due to the contralesional hindlimb flexion and persisted after decerebration and complete spinal cord transection. The asymmetry induced by the left-side brain injury was eliminated by bilateral lumbar dorsal rhizotomy, but surprisingly, the asymmetry after the right-side brain lesion was resistant to deafferentation. Pancuronium, a curare-mimetic muscle relaxant, abolished the asymmetry after the right-side lesion suggesting its dependence on the efferent drive. The contra- and ipsilesional hindlimbs displayed different musculo-articular resistance to stretch after the left but not right-side injury. The nociceptive withdrawal reflexes evoked by electrical stimulation and recorded with EMG technique were different between the left and right hindlimbs in the spinalized decerebrate rats. On this asymmetric background, a brain injury resulted in greater reflex activation on the contra- versus ipsilesional side; the difference between the limbs was higher after the right-side brain lesion. The unilateral brain injury modified expression of neuroplasticity genes analysed as readout of plastic changes, as well as robustly impaired coordination of their expression within and between the ipsi- and contralesional halves of lumbar spinal cord; the effects were more pronounced after the left side compared to the right-side injury. Our data suggest that changes in the hindlimb posture, resistance to stretch and nociceptive withdrawal reflexes are encoded by neuroplastic processes in lumbar spinal circuits induced by a unilateral brain injury. Two mechanisms, one dependent on and one independent of afferent input may mediate asymmetric hindlimb motor responses. The latter, deafferentation resistant mechanism may be based on sustained muscle contractions which often occur in patients with central lesions and which are not evoked by afferent stimulation. The unusual feature of these mechanisms is their lateralization in the spinal cord.

scholarly journals Ipsilesional versus contralesional postural deficits induced by unilateral brain trauma: a side reversal by opioid mechanism

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Hiroyuki Watanabe ◽  
Olga Nosova ◽  
Daniil Sarkisyan ◽  
Marlene Storm Andersen ◽  
Mengliang Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Brain Injury ◽  
Brain Trauma ◽  
Spinal Cord Transection ◽  
Postural Asymmetry ◽  
Left Limb ◽  
The Asymmetry ◽  
Limb Flexion ◽  
Unilateral Brain

Abstract Unilateral traumatic brain injury and stroke result in asymmetric postural and motor deficits including contralateral hemiplegia and hemiparesis. In animals, a localized unilateral brain injury recapitulates the human upper motor neuron syndrome in the formation of hindlimb postural asymmetry with contralesional limb flexion and the asymmetry of hindlimb nociceptive withdrawal reflexes. The current view is that these effects are developed due to aberrant activity of motor pathways that descend from the brain into the spinal cord. These pathways and their target spinal circuits may be regulated by local neurohormonal systems that may also mediate effects of brain injury. Here, we evaluate if a unilateral traumatic brain injury induces hindlimb postural asymmetry, a model of postural deficits, and if this asymmetry is spinally encoded and mediated by the endogenous opioid system in rats. A unilateral right-sided controlled cortical impact, a model of clinical focal traumatic brain injury was centred over the sensorimotor cortex and was observed to induce hindlimb postural asymmetry with contralateral limb flexion. The asymmetry persisted after complete spinal cord transection, implicating local neurocircuitry in the development of the deficits. Administration of the general opioid antagonist naloxone and μ-antagonist β-funaltrexamine blocked the formation of postural asymmetry. Surprisingly, κ-antagonists nor-binaltorphimine and LY2444296 did not affect the asymmetry magnitude but reversed the flexion side; instead of contralesional (left) hindlimb flexion the ipsilesional (right) limb was flexed. The postural effects of the right-side cortical injury were mimicked in animals with intact brain via intrathecal administration of the opioid κ-agonist (2)-(trans)-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidiny)-cyclohexyl]benzeneacetamide that induced hindlimb postural asymmetry with left limb flexion. The δ-antagonist naltrindole produced no effect on the contralesional (left) flexion but inhibited the formation of the ipsilesional (right) limb flexion in brain-injured rats that were treated with κ-antagonist. The effects of the antagonists were evident before and after spinal cord transection. We concluded that the focal traumatic brain injury-induced postural asymmetry was encoded at the spinal level, and was blocked or its side was reversed by administration of opioid antagonists. The findings suggest that the balance in activity of the mirror symmetric spinal neural circuits regulating contraction of the left and right hindlimb muscles is controlled by different subtypes of opioid receptors; and that this equilibrium is impaired after unilateral brain trauma through side-specific opioid mechanism.

scholarly journals Endocrine signaling mediates asymmetric motor deficits after unilateral brain injury

2020 ◽  
Author(s):  
Nikolay Lukoyanov ◽  
Hiroyuki Watanabe ◽  
Liliana S. Carvalho ◽  
Olga Nosova ◽  
Daniil Sarkisyan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Injury ◽  
Neural Control ◽  
Expression Patterns ◽  
Lumbar Spinal Cord ◽  
Motor Deficits ◽  
Postural Asymmetry ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Unilateral Brain

AbstractA paradigm in neurology is that brain injury-induced motor deficits (e.g. hemiparesis and hemiplegia) arise due to aberrant activity of descending neural pathways. We discovered that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion, and asymmetric changes in nociceptive hindlimb withdrawal reflexes and gene expression patterns in lumbar spinal cord. The injury-induced postural effects were abolished by prior hypophysectomy and were mimicked by transfusion of serum from animals with unilateral brain injury. Antagonists of the opioid and vasopressin receptors blocked formation of hindlimb postural asymmetry suggesting that these neurohormones mediate effects of brain injury on lateralized motor responses. Our data indicate that descending neural control of spinal circuits is complemented by a previously unknown humoral signaling from injured brain to the contra- and ipsilesional hindlimbs, and suggest the existence of a body side-specific neuroendocrine regulation in bilaterally symmetric animals.

scholarly journals Coordinated expression of the renin‐angiotensin genes in the lumbar spinal cord: lateralization and effects of unilateral brain injury

2021 ◽  
Author(s):  
Georgy Bakalkin ◽  
Anika Kahle ◽  
Daniil Sarkisyan ◽  
Hiroyuki Watanabe ◽  
Nikolay Lukoyanov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Injury ◽  
Lumbar Spinal Cord ◽  
Renin Angiotensin ◽  
Coordinated Expression ◽  
Lumbar Spinal ◽  
Unilateral Brain

scholarly journals Left-right side-specific endocrine signaling complements neural pathways to mediate acute asymmetric effects of brain injury

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Nikolay Lukoyanov ◽  
Hiroyuki Watanabe ◽  
Liliana S Carvalho ◽  
Olga Kononenko ◽  
Daniil Sarkisyan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Injury ◽  
Brain Injuries ◽  
Expression Patterns ◽  
Lumbar Spinal Cord ◽  
Neural Pathways ◽  
Postural Asymmetry ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Lumbar Spinal

Brain injuries can interrupt descending neural pathways that convey motor commands from the cortex to spinal motoneurons. Here, we demonstrate that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion and asymmetric hindlimb withdrawal reflexes within 3 hr, as well as asymmetry in gene expression patterns in the lumbar spinal cord. The injury-induced postural effects were abolished by hypophysectomy and were mimicked by transfusion of serum from animals with brain injury. Administration of the pituitary neurohormones β-endorphin or Arg-vasopressin-induced side-specific hindlimb responses in naive animals, while antagonists of the opioid and vasopressin receptors blocked hindlimb postural asymmetry in rats with brain injury. Thus, in addition to the well-established involvement of motor pathways descending from the brain to spinal circuits, the side-specific humoral signaling may also add to postural and reflex asymmetries seen after brain injury.

Blink-associated contralateral eccentric saccades as a rare sign of unilateral brain injury

Neurology ◽  
2016 ◽  
Vol 88 (2) ◽  
pp. 160-163 ◽  
Author(s):  
Ilaria Zivi ◽  
Eugenio Bertelli ◽  
Giacinta Bilotti ◽  
Ignazio Alessandro Clemente ◽  
Leopold Saltuari ◽  
...  
Keyword(s):  
Brain Injury ◽  
Evoked Potentials ◽  
Brain Mri ◽  
Neural Pathways ◽  
Cerebral Lesions ◽  
Infrared Video ◽  
Corrective Movement ◽  
The Right ◽  
Mri Study ◽  
Unilateral Brain

Objective:To describe a rare sign of unilateral brain injury as a form of unwanted blink-associated contralateral eccentric saccades.Methods:A 62-year-old patient who underwent an ischemic stroke affecting the entire right middle cerebral artery territory came to our attention 1 year after stroke, manifesting with transient contralateral conjugate gaze deviations associated with spontaneous blinking. We complemented the regular neurologic evaluation with brain MRI, study of evoked potentials, electroneurography of the facial nerve, and infrared video-oculoscopy.Results:The patient had left-sided hemiparesis, hypoesthesia, hemianopia, and hemispatial neglect. He also showed the occurrence of a rapid leftward conjugate deviation of the eyes, followed by a corrective movement to the primary ocular position. MRI showed a wide malacic area spanning the right frontal, temporal, and parietal cortical and subcortical regions, with signs of wallerian degeneration of the descending right corticospinal tract. Motor and somatosensory evoked potentials were centrally altered on the right side. Electroneurography of the facial nerves was normal. Infrared video-oculoscopy indicated persistence of the same blink-related saccades even in darkness.Conclusions:It is known that unilateral cerebral lesions may manifest with a contralateral conjugate gaze deviation evoked by closure of the lids. This sign, known as spasticity of conjugate gaze, may be due to the suppression of the fixation reflex. In our case, the persistence of this sign in the darkness allowed us to exclude this diagnosis. We hypothesized that the blink-related neural pathways may improperly activate the oculomotor circuitry at both the cortical and subcortical levels.

scholarly journals Focal traumatic brain injury induces neuroplastic molecular responses in lumbar spinal cord

2019 ◽  
Vol 37 (2) ◽  
pp. 87-96
Author(s):  
Olga Kononenko ◽  
Hiroyuki Watanabe ◽  
Lada Stålhandske ◽  
Ann Zarelius ◽  
Fredrik Clausen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Brain Injury ◽  
Lumbar Spinal Cord ◽  
Molecular Responses ◽  
Lumbar Spinal

scholarly journals The "eye sign" due to hemispatial neglect: A case report

2009 ◽  
Vol 3 (3) ◽  
pp. 256-259 ◽  
Author(s):  
Fábio Henrique de Gobbi Porto ◽  
Gislaine Cristina Lopes Machado ◽  
Mari-Nilva Maia da Silva ◽  
Gabriel Rodriguez de Freitas
Keyword(s):  
Case Report ◽  
Brain Damage ◽  
Motor Deficits ◽  
Frontal Eye Fields ◽  
Hemispatial Neglect ◽  
Attention Network ◽  
Unilateral Brain Damage ◽  
Horizontal Gaze ◽  
The Right ◽  
Unilateral Brain

Abstract Conjugate eye deviation is characterized by a sustained shift in horizontal gaze, usually toward the affected brain hemisphere. When detected on neuroimaging, it is called the "eye sign". It is classically associated with lesions involving the frontal eye fields, ipsilateral to the side of the deviation. Neglect may be conceptualized as a spatially addressed bias of the sensory events in explicit behaviors and in the absence of perceptual and motor deficits. Hemispatial neglect is a common disabling condition that occurs following acute unilateral brain damage, usually to the right side. We report a case of a patient presenting with the "eye sign" on tomography, following an acute subinsular stroke, in the absence of conjugated eyes deviation. Our hypothesis was that the sign may have been due to hemispatial neglect in this patient. The aim of this article was to discuss the mechanisms involved in the attention network and its neuroanatomic correlates.

scholarly journals Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6250
Author(s):  
Yu-Hsin Chen ◽  
Yen-Chou Chen ◽  
Ling-Ling Hwang ◽  
Liang-Yo Yang ◽  
Dah-Yuu Lu
Keyword(s):  
Brain Injury ◽  
Motor Function ◽  
Brain Injuries ◽  
Brain Lesion ◽  
Motor Deficits ◽  
Breakdown Product ◽  
Lesion Volume ◽  
Wild Type ◽  
Neuroprotective Effects

Androgens have been shown to have a beneficial effect on brain injury and lower reactive astrocyte expression after TBI. Androgen receptors (ARs) are known to mediate the neuroprotective effects of androgens. However, whether ARs play a crucial role in TBI remains unknown. In this study, we investigated the role of ARs in TBI pathophysiology, using AR knockout (ARKO) mice. We used the controlled cortical impact model to produce primary and mechanical brain injuries and assessed motor function and brain-lesion volume. In addition, the AR knockout effects on necrosis and autophagy were evaluated after TBI. AR knockout significantly increased TBI-induced expression of the necrosis marker alpha-II-spectrin breakdown product 150 and astrogliosis marker glial fibrillary acidic protein. In addition, the TBI-induced astrogliosis increase in ARKO mice lasted for three weeks after a TBI. The autophagy marker Beclin-1 was also enhanced in ARKO mice compared with wild-type mice after TBI. Our results also indicated that ARKO mice showed a more unsatisfactory performance than wild-type mice in a motor function test following TBI. Further, they were observed to have more severe lesions than wild-type mice after injury. These findings strongly suggest that ARs play a role in TBI.

scholarly journals A Novel Anti-Inflammatory d-Peptide Inhibits Disease Phenotype Progression in an ALS Mouse Model

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1590
Author(s):  
Julia Post ◽  
Vanessa Kogel ◽  
Anja Schaffrath ◽  
Philipp Lohmann ◽  
Nadim Joni Shah ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mouse Model ◽  
Brain Stem ◽  
Motor Coordination ◽  
Therapeutic Potential ◽  
Lumbar Spinal Cord ◽  
Motor Deficits ◽  
Disease Phenotype ◽  
Lumbar Spinal ◽  
The Brain

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by selective neuronal death in the brain stem and spinal cord. The cause is unknown, but an increasing amount of evidence has firmly certified that neuroinflammation plays a key role in ALS pathogenesis. Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and has been implicated as driver of disease progression. Here, we describe a treatment study demonstrating the therapeutic potential of a tandem version of the well-known all-d-peptide RD2 (RD2RD2) in a transgenic mouse model of ALS (SOD1*G93A). Mice were treated intraperitoneally for four weeks with RD2RD2 vs. placebo. SOD1*G93A mice were tested longitudinally during treatment in various behavioural and motor coordination tests. Brain and spinal cord samples were investigated immunohistochemically for gliosis and neurodegeneration. RD2RD2 treatment in SOD1*G93A mice resulted not only in a reduction of activated astrocytes and microglia in both the brain stem and lumbar spinal cord, but also in a rescue of neurons in the motor cortex. RD2RD2 treatment was able to slow progression of the disease phenotype, especially the motor deficits, to an extent that during the four weeks treatment duration, no significant progression was observed in any of the motor experiments. Based on the presented results, we conclude that RD2RD2 is a potential therapeutic candidate against ALS.

scholarly journals Spinal cord tumor hidden by comorbidities

2015 ◽  
Vol 10 (4) ◽  
pp. 400-403
Author(s):  
Gabriela MIHĂILESCU ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Spinal Cord ◽  
Spinal Cord Tumor ◽  
Cervical Region ◽  
Motor Deficits ◽  
Nonvalvular Atrial Fibrillation ◽  
Clinical Neurological Examination ◽  
Anticoagulant Drugs ◽  
The Right ◽  
High Cervical

Comorbidities present in complex cases can frequently hide new diseases, may influence treatment decisions and can augment risks. The nonvalvular atrial fibrillation is a risk factor for inducing stroke, but treated with anticoagulant drugs in a right way atrial fibrillation is not responsible for the onset of all new motor deficits in a patient. The anamnesis, the thorough clinical neurological examination, associated with specific paraclinical diagnosis methods can lead to the right diagnosis, showing, in this specific case presented, a meningioma of the spinal cord localised in the high cervical region, treated by neurosurgery.

Sign in / Sign up

Export Citation Format

Share Document