scholarly journals Persistent beneficial impact of H-reflex conditioning in spinal cord-injured rats

2014 ◽  
Vol 112 (10) ◽  
pp. 2374-2381 ◽  
Author(s):  
Yi Chen ◽  
Lu Chen ◽  
Yu Wang ◽  
Jonathan R. Wolpaw ◽  
Xiang Yang Chen
Keyword(s):  
Spinal Cord ◽  
H Reflex ◽  
Spinal Reflex ◽  
Spinal Cord Regeneration ◽  
Lateral Column ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Beneficial Impact ◽  
The Right ◽  
Spinal Cord Injured

Operant conditioning of a spinal cord reflex can improve locomotion in rats and humans with incomplete spinal cord injury. This study examined the persistence of its beneficial effects. In rats in which a right lateral column contusion injury had produced asymmetric locomotion, up-conditioning of the right soleus H-reflex eliminated the asymmetry while down-conditioning had no effect. After the 50-day conditioning period ended, the H-reflex was monitored for 100 [±9 (SD)] (range 79–108) more days and locomotion was then reevaluated. After conditioning ended in up-conditioned rats, the H-reflex continued to increase, and locomotion continued to improve. In down-conditioned rats, the H-reflex decrease gradually disappeared after conditioning ended, and locomotion at the end of data collection remained as impaired as it had been before and immediately after down-conditioning. The persistence (and further progression) of H-reflex increase but not H-reflex decrease in these spinal cord-injured rats is consistent with the fact that up-conditioning improved their locomotion while down-conditioning did not. That is, even after up-conditioning ended, the up-conditioned H-reflex pathway remained adaptive because it improved locomotion. The persistence and further enhancement of the locomotor improvement indicates that spinal reflex conditioning protocols might supplement current therapies and enhance neurorehabilitation. They may be especially useful when significant spinal cord regeneration becomes possible and precise methods for retraining the regenerated spinal cord are needed.

scholarly journals Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury

2014 ◽  
Vol 111 (6) ◽  
pp. 1249-1258 ◽  
Author(s):  
Yi Chen ◽  
Lu Chen ◽  
Rongliang Liu ◽  
Yu Wang ◽  
Xiang Yang Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
H Reflex ◽  
Spinal Reflex ◽  
Step Cycle ◽  
Reflex Pathway ◽  
Cord Injury ◽  
Kinematic Analyses ◽  
Spinal Cord Contusion ◽  
The Right ◽  
The Impact

When new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a “negotiated equilibrium” that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery.

scholarly journals Regenerative therapy for spinal cord injury using iPSC technology

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Narihito Nagoshi ◽  
Hideyuki Okano ◽  
Masaya Nakamura
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Chronic Phase ◽  
Regenerative Therapy ◽  
Spinal Cord Regeneration ◽  
Gamma Secretase ◽  
Safety Issues ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Induced Pluripotent

Abstract Spinal cord injury (SCI) is a devastating event that causes permanent neurologic impairments. Cell transplantation therapy using neural precursor cells (NPCs) is a promising intervention aiming to replace damaged neural tissue and restore certain functions. Because the protocol to produce human induced pluripotent stem cells (iPSCs) was first established, we have attempted to apply this technology for regenerative therapy in SCI. Our group reported beneficial effects of iPSC-derived NPC transplantation and addressed safety issues on tumorigenicity after grafting. These findings will soon be tested at the clinical trial stage, the protocol of which has already been approved by the Ministry of Health, Labour and Welfare in Japan. Current transplantation therapies treat patients at the subacute phase after injury, highlighting the need for effective treatments for chronic SCI. We recently demonstrated the modest efficacy of gamma secretase inhibitor treatment of iPSC-NPCs before transplantation at the chronic phase. However, more comprehensive strategies involving combinatory therapies are essential to enhance current spinal cord regeneration treatments.

The management of fertility in spinal cord injury

2017 ◽  
Author(s):  
Mikkel Fode ◽  
Jens Sønksen
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Semen Quality ◽  
Sperm Quality ◽  
Sperm Count ◽  
Autonomic Nerve ◽  
Sperm Retrieval ◽  
Cord Injury ◽  
The Right ◽  
Spinal Cord Injured

While spinal cord injury (SCI) does not affect female fertility, the condition most often results in infertility in males due to anejaculation and reduced semen quality. Anejaculation is caused by disruption of the autonomic nerve fibres, which are normally responsible for the ejaculation. The reason for the poor sperm quality has not been firmly established. If spinal cord injured men cannot ejaculate by sexual intercourse or masturbation, ejaculation can be induced by either penile vibratory stimulation or electroejaculation. Only if these methods fail should surgical sperm retrieval be considered. The method of insemination depends largely on the total motile sperm count and patient preference. With the right treatment, it is possible for most SCI men to have children.

Probable Corticospinal Tract Control of Spinal Cord Plasticity in the Rat

2002 ◽  
Vol 87 (2) ◽  
pp. 645-652 ◽  
Author(s):  
Xiang Yang Chen ◽  
Jonathan R. Wolpaw
Keyword(s):  
Spinal Cord ◽  
Corticospinal Tract ◽  
Recovery Of Function ◽  
Dorsal Column ◽  
H Reflex ◽  
Sprague Dawley ◽  
Lateral Column ◽  
Gradual Loss ◽  
Cord Injury ◽  
Spinal Stretch Reflex

Descending activity from the brain shapes spinal cord reflex function throughout life, yet the mechanisms responsible for this spinal cord plasticity are poorly understood. Operant conditioning of the H-reflex, the electrical analogue of the spinal stretch reflex, is a simple model for investigating these mechanisms. An earlier study in the Sprague-Dawley rat showed that acquisition of an operantly conditioned decrease in the soleus H-reflex is not prevented by mid-thoracic transection of the ipsilateral lateral column (LC), which contains the rubrospinal, reticulospinal, and vestibulospinal tracts, and is prevented by transection of the dorsal column, which contains the main corticospinal tract (CST) and the dorsal column ascending tract (DA). The present study explored the effects of CST or DA transection on acquisition of an H-reflex decrease, and the effects of LC, CST, or DA transection on maintenance of an established decrease. CST transection prior to conditioning prevented acquisition of H-reflex decrease, while DA transection did not do so. CST transection after H-reflex decrease had been acquired led to gradual loss of the decrease over 10 days, and resulted in an H-reflex that was significantly larger than the original, naive H-reflex. In contrast, LC or DA transection after H-reflex decrease had been acquired did not affect maintenance of the decrease. These results, in combination with the earlier study, strongly imply that in the rat the corticospinal tract (CST) is essential for acquisition and maintenance of operantly conditioned decrease in the H-reflex and that other major spinal cord pathways are not essential. This previously unrecognized aspect of CST function gives insight into the processes underlying acquisition and maintenance of motor skills and could lead to novel methods for inducing, guiding, and assessing recovery of function after spinal cord injury.

scholarly journals Operant Conditioning of Reciprocal Inhibition in Rat Soleus Muscle

2006 ◽  
Vol 96 (4) ◽  
pp. 2144-2150 ◽  
Author(s):  
Xiang Yang Chen ◽  
Lu Chen ◽  
Yi Chen ◽  
Jonathan R. Wolpaw
Keyword(s):  
Spinal Cord ◽  
Operant Conditioning ◽  
Reciprocal Inhibition ◽  
H Reflex ◽  
Spinal Reflex ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cord Injury ◽  
Rat Soleus Muscle ◽  
Spinal Stretch Reflex

Operant conditioning of the H-reflex, the electrical analog of the spinal stretch reflex (SSR), induces activity-dependent plasticity in the spinal cord and might be used to improve locomotion after spinal cord injury. To further assess the potential clinical significance of spinal reflex conditioning, this study asks whether another well-defined spinal reflex pathway, the disynaptic pathway underlying reciprocal inhibition (RI), can also be operantly conditioned. Sprague-Dawley rats were implanted with electromyographic (EMG) electrodes in right soleus (SOL) and tibialis anterior (TA) muscles and a stimulating cuff on the common peroneal (CP) nerve. When background EMG in both muscles remained in defined ranges, CP stimulation elicited the TA H-reflex and SOL RI. After collection of control data for 20 days, each rat was exposed for 50 days to up-conditioning (RIup mode) or down-conditioning (RIdown mode) in which food reward occurred if SOL RI evoked by CP stimulation was more (RIup mode) or less (RIdown mode) than a criterion. TA and SOL background EMG and TA M response remained stable. In every rat, RI conditioning was successful (i.e., change ≥20% in the correct direction). In the RIup rats, final SOL RI averaged 171± 28% (mean ± SE) of control, and final TA H-reflex averaged 114 ± 14%. In the RIdown rats, final SOL RI averaged 37 ± 13% of control, and final TA H-reflex averaged 60 ± 18%. Final SOL RI and TA H-reflex sizes were significantly correlated. Thus like the SSR and the H-reflex, RI can be operantly conditioned; and conditioning one reflex can affect another reflex as well.

Conditioned H-Reflex Increase Persists After Transection of the Main Corticospinal Tract in Rats

2003 ◽  
Vol 90 (5) ◽  
pp. 3572-3578 ◽  
Author(s):  
Xiang Yang Chen ◽  
Lu Chen ◽  
Jonathan R. Wolpaw
Keyword(s):  
Spinal Cord ◽  
Operant Conditioning ◽  
Corticospinal Tract ◽  
Dorsal Column ◽  
H Reflex ◽  
Initial Value ◽  
Cord Injury ◽  
Training Mode ◽  
The Right ◽  
Spinal Stretch Reflex

The brain shapes spinal cord function throughout life. Operant conditioning of the H-reflex, the electrical analog of the spinal stretch reflex (SSR), is a relatively simple model for exploring the spinal cord plasticity underlying this functional change and may provide a new method for modifying spinal cord reflexes after spinal cord injury. In response to an operant conditioning protocol, rats can gradually increase (i.e., up-training mode) or decrease (i.e., down-training mode) the soleus H-reflex. This study explored the effects of midthoracic transection of the ipsilateral lateral column (LC) (rubrospinal, vestibulospinal, and reticulospinal tracts), the dorsal column corticospinal tract (CST), or the dorsal column ascending tract (DA) on maintenance of an H-reflex increase that has already occurred. Rats were implanted with EMG electrodes in the right soleus muscle and a nerve-stimulating cuff on the right posterior tibial nerve. After initial (i.e., control) H-reflex size was determined, the rats were exposed for 50 days to the up-training mode, in which reward was given when the H-reflex was above a criterion value. H-reflex size gradually rose to 168 ± 12% (mean ± SE) of its initial value. Each rat then received an LC, CST, or DA transection and continued under the up-training mode for 50 more days. None of the transections abolished the H-reflex increase. H-reflex size increased further to 197 ± 19% of its initial value and did not differ significantly among LC, CST, and DA rats ( P > 0.78 by ANOVA). Although earlier studies show that the main CST is needed for acquisition of H-reflex up-training and down-training and for maintenance of down-training, this study shows that it is not needed for maintenance of up-training. It adds to the evidence that H-reflex conditioning changes the spinal cord and that the spinal cord plasticity associated with up-training is different from that associated with down-training.

Caloric Stimulation-induced Augmentation of H-Reflexes in Normal Subjects, but Not in Spinal Cord-injured Patients

Neurosurgery ◽  
1984 ◽  
Vol 14 (5) ◽  
pp. 562-566 ◽  
Author(s):  
Maureen Raffensperger ◽  
Donald H. York
Keyword(s):  
Spinal Cord ◽  
Clinical Signs ◽  
Normal Subjects ◽  
H Reflex ◽  
Reflex Amplitude ◽  
Caloric Stimulation ◽  
Cord Injury ◽  
Injured Patients ◽  
Ice Water ◽  
Spinal Cord Injured

Abstract This study examined the effects of ice water caloric stimulation on H-reflex amplitude in normal subjects and three complete spinal cord-injured patients. H-reflexes were obtained by stimulating the tibial nerve at the popliteal fossa and recording the H-response from the gastrocnemius muscle. All normal subjects who experienced nystagmus or vertigo demonstrated significant augmentation in H-reflex amplitude with ice water irrigation of the ear canal. In the three spinal cord-injured patients, there was no significant change of H-reflex with the ice water stimulus. The results suggest that descending tracts in the anterior spinal cord must be functional to demonstrate caloric augmentation of H-reflexes. In patients with spinal cord injury, it may be possible to predict the recovery of motor function using this test together with other clinical signs of neurological function.

scholarly journals Neuronal Actions of Transspinal Stimulation on Locomotor Networks and Reflex Excitability During Walking in Humans With and Without Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Md. Anamul Islam ◽  
Timothy S. Pulverenti ◽  
Maria Knikou
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Single Pulse ◽  
H Reflex ◽  
Spinal Reflex ◽  
Emg Activity ◽  
Step Cycle ◽  
Reflex Excitability ◽  
Cord Injury ◽  
Modulation Pattern

This study investigated the neuromodulatory effects of transspinal stimulation on soleus H-reflex excitability and electromyographic (EMG) activity during stepping in humans with and without spinal cord injury (SCI). Thirteen able-bodied adults and 5 individuals with SCI participated in the study. EMG activity from both legs was determined for steps without, during, and after a single-pulse or pulse train transspinal stimulation delivered during stepping randomly at different phases of the step cycle. The soleus H-reflex was recorded in both subject groups under control conditions and following single-pulse transspinal stimulation at an individualized exactly similar positive and negative conditioning-test interval. The EMG activity was decreased in both subject groups at the steps during transspinal stimulation, while intralimb and interlimb coordination were altered only in SCI subjects. At the steps immediately after transspinal stimulation, the physiological phase-dependent EMG modulation pattern remained unaffected in able-bodied subjects. The conditioned soleus H-reflex was depressed throughout the step cycle in both subject groups. Transspinal stimulation modulated depolarization of motoneurons over multiple segments, limb coordination, and soleus H-reflex excitability during assisted stepping. The soleus H-reflex depression may be the result of complex spinal inhibitory interneuronal circuits activated by transspinal stimulation and collision between orthodromic and antidromic volleys in the peripheral mixed nerve. The soleus H-reflex depression by transspinal stimulation suggests a potential application for normalization of spinal reflex excitability after SCI.

scholarly journals Reduction of spinal sensory transmission by facilitation of 5-HT1B/D receptors in noninjured and spinal cord-injured humans

2013 ◽  
Vol 109 (6) ◽  
pp. 1485-1493 ◽  
Author(s):  
Jessica M. D'Amico ◽  
Yaqing Li ◽  
David J. Bennett ◽  
Monica A. Gorassini
Keyword(s):  
Spinal Cord ◽  
H Reflex ◽  
Controlled Study ◽  
Double Blind ◽  
Afferent Pathways ◽  
Persistent Inward Currents ◽  
Sensory Transmission ◽  
Cord Injury ◽  
Inward Currents ◽  
Spinal Cord Injured

Activation of receptors by serotonin (5-HT1) and norepinephrine (α2) on primary afferent terminals and excitatory interneurons reduces transmission in spinal sensory pathways. Loss or reduction of descending sources of serotonin and norepinephrine after spinal cord injury (SCI) and the subsequent reduction of 5-HT1/α2 receptor activity contributes, in part, to the emergence of excessive motoneuron activation from sensory afferent pathways and the uncontrolled triggering of persistent inward currents that depolarize motoneurons during muscle spasms. We tested in a double-blind, placebo-controlled study whether facilitating 5-HT1B/D receptors with the agonist zolmitriptan reduces the sensory activation of motoneurons during an H-reflex in both noninjured control and spinal cord-injured participants. In both groups zolmitriptan, but not placebo, reduced the size of the maximum soleus H-reflex with a peak decrease to 59% (noninjured) and 62% (SCI) of predrug values. In SCI participants we also examined the effects of zolmitriptan on the cutaneomuscular reflex evoked in tibialis anterior from stimulation to the medial arch of the foot. Zolmitriptan, but not placebo, reduced the long-latency, polysynaptic component of the cutaneomuscular reflex (first 200 ms of reflex) by ∼50%. This ultimately reduced the triggering of the long-lasting component of the reflex (500 ms poststimulation to end of reflex) known to be mediated by persistent inward currents in the motoneuron. These results demonstrate that facilitation of 5-HT1B/D receptors reduces sensory transmission in both monosynaptic and polysynaptic reflex pathways to ultimately reduce long-lasting reflexes (spasms) after SCI.

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