Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Early-phase rotator training impairs tissue repair and functional recovery after spinal cord injury.

Spinal cord injury (SCI) is a devastating disorder that often results in severe sensorimotor function impairment with limited recovery of function. In recent years, rehabilitation training for spinal cord injury has gradually emerged, and some of them play an important role in the repair of spinal cord injury However, the optimal training regimen for SCI remains to be determined. In this study, we explore the effects of rotarod training (began at 7 days post-injury) on the recovery of motor function after SCI, as well as its possible repair mechanism from the aspects of function and histopathological changes, the behaviors of specific trophic factors and cytokines, and the expression profile of specific genes. Multiple functional assessments showed that rotarod training initiated at 7 days post-injury is unsuitable for promoting neuro-electrophysiological improvement and trunk stability, but impaired functional coordination and motor recovery. In addition, rotarod training has negative effects on spinal cord repair after SCI, which is manifested as an increase of lesion area, a decrease in neuronal viability, a deterioration in immuno-microenvironment and remyelination, a significant reduction in the expression of trophic factors and an increase in the expression of pro-inflammatory factors. RNA sequencing suggested that the genes associated with angiogenesis and synaptogenesis were significantly downregulated and the PI3K-AKT pathway was inhibited, which was detrimental to spinal cord repair and impeded nerve regeneration. These results indicate that immediate rotarod training after SCI is currently unsuitable for rehabilitation in mice.

Suppression of Microglial ERO1a Alleviates Inflammation and Enhances the Efficacy of Rehabilitative Training After Ischemic Stroke.

Microglia mediated inflammation plays a crucial role in cellular events and functional recovery post ischemic stroke. In the current study, we profiled the proteome changes of microglia treated with oxygen and glucose deprivation (OGD). Bioinformatics analysis identified that differentially expressed proteins (DEPs) were enriched in pathways associated with oxidate phosphorylation and mitochondrial respiratory chain at both 6h and 24h post OGD. We next focused on one validated target named endoplasmic reticulum oxidoreductase 1 alpha (ERO1a) to study its role in stroke pathophysiology. We showed that over-expression of microglial ERO1a exacerbated inflammation, cell apoptosis and behavioral outcomes post middle cerebral artery occlusion (MCAO). In contrast, suppression of microglial ERO1a significantly reduced activation of both microglia and astrocyte, along with cell apoptosis. Furthermore, knocking down microglial ERO1a improved the efficacy of rehabilitative training and enhanced the mTOR activity in spared corticospinal neurons. Our study provided novel insights into the identification of therapeutic targets and the design of rehabilitative protocols to treat ischemic stroke and other traumatic CNS injuries.

Effects of task-based rehabilitative training combined with PTEN/SOCS3 coinhibition promotes axon regeneration and upper extremity skilled motor function recovery after cervical spinal cord injury in adult mice.

Previous studies reported that the codeletion of PTEN and SOCS3 can greatly enhance the capacity of axon regeneration after central nervous system (CNS) injury. Moreover, the promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism after CNS injury. However, few studies have reported the interaction between these mechanisms after spinal cord injury (SCI). Therefore, we investigated the combined effects of PTEN/SOCS3 coinhibition and rehabilitative training on axon regeneration and upper extremity motor functional improvement after cervical SCI in mice. In this study, we used RNA interference viruses to coinhibit PTEN and SOCS3 and induced a C5 crush injury on the side of preference. The injured upper extremity was trained by single pellet grasping for 4 weeks. We found that the coinjection of viruses significantly increased the expression of p-S6 and p-STAT in the cortex, reduced the dieback pattern of injured axons and promoted traced axon regeneration. More importantly, combination therapy further enhanced axon regeneration compared with PTEN/SOCS3 coinhibition alone. In behavioral tests, the motor performance of the mice in the PTEN/SOCS3 + Training group was better than that of the mice in the other groups. These results indicate that combining task-based rehabilitative training with PTEN/SOCS3 coinhibition further promotes axon regeneration and significant improvement in forelimb skilled motor function after cervical SCI. Our findings provide new therapeutic insights into SCI treatment.

Rehabilitative Training Enhances Therapeutic Effect of Human-iPSC-Derived Neural Stem/Progenitor Cells Transplantation in Chronic Spinal Cord Injury.

Cell transplantation therapy using human-induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a new therapeutic strategy for spinal cord injury (SCI). Preclinical studies have demonstrated the efficacy of hiPSC-NS/PCs transplantation in the subacute phase of SCI. However, locomotor recovery secondary to hiPSC-NS/PCs transplantation is limited in the chronic phase, suggesting that additional treatment, including rehabilitative training, is required to ensure recovery. The therapeutic potential of hiPSC-NS/PCs that qualify for clinical application is yet to be fully delineated. Therefore, in this study, we investigated the therapeutic effect of the combined therapy of clinical-grade hiPSC-NS/PCs transplantation and rehabilitative training that could produce synergistic effects in a rodent model of chronic SCI. Our findings indicated that rehabilitative training promoted the survival rate and neuronal differentiation of transplanted hiPSC-NS/PCs. The combination therapy was able to enhance the expressions of the BDNF and NT-3 proteins in the spinal cord tissue. Moreover, rehabilitation promoted neuronal activity and increased 5-HT-positive fibers at the lumbar enlargement. Consequently, the combination therapy significantly improved motor functions. The findings of this study suggest that the combined therapy of hiPSC-NS/PCs transplantation and rehabilitative training has the potential to promote functional recovery even when initiated during chronic SCI.

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury.

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability.

Combining task-based rehabilitative training with PTEN inhibition promotes axon regeneration and upper extremity skilled motor function recovery after cervical spinal cord injury in adult mice.

BACKGROUND: Conditional deletion of Pten in corticospinal neurons promotes axon sprouting and regeneration after spinal cord injury (SCI). However, regeneration studies targeted on PTEN inhibition seldom show motor function recovery. The promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism. PURPOSE: To investigate the combined effects of PTEN inhibition and rehabilitative training on axon regeneration and subsequent motor functional improvement after cervical spinal cord injury. METHODS: Lentiviral particles (Lenti-PTEN-RNAi or Lenti-Scrambled-EGFP) were injected into the right sensorimotor mouse cortex in four experimental groups (PTEN RNAi + Training, PTEN RNAi, Control + Training, Control). Two weeks after injection, all mouse groups received a left C5 crush injury. We performed task-based rehabilitative training for 4 weeks on the PTEN RNAi + Training and Control + Training groups. Biotinylated dextran amine (BDA) was used for anterograde tracing of the dorsal corticospinal tract (dCST). We analysed axonal regeneration through immunohistochemical methods. A battery of behavioral tests was employed to assess functional recovery at Day3 and every other week after injury. RESULTS: Combining rehabilitative training with PTEN inhibition induced more axon regeneration and synapse reformation in the spinal cord caudal to the lesion site. Rostral to the lesion, the transected dCST axons sprouted into gray matter upon contact. Furthermore, forelimb function was found to be improved after combination therapy during behavioral testing. CONCLUSION: Combining task-based rehabilitative training with PTEN inhibition further promotes axon regeneration, synaptic plasticity and reorganization of the neural network, with significant improvement in forelimb skilled motor function after cervical spinal cord injury. Our study provides new therapeutic insights for spinal cord injury management in the future.

Training in a cooperative bimanual skilled reaching task, the popcorn retrieval task, improves unimanual function after motor cortical infarcts in rats.

Disuse of the paretic hand after stroke is encouraged by compensatory reliance on the nonparetic hand, to exacerbate impairment and potentially constrain motor rehabilitation efficacy. Rodent stroke model findings support that learning new unimanual skills with the nonparetic forelimb diminishes functional improvements that can be driven by rehabilitative training of the paretic forelimb. The influence of learning new ways of skillfully using the two hands together on paretic side function is much less clear. To begin to explore this, we developed a new cooperative bimanual skilled reaching task for rats, the Popcorn Retrieval Task. After motor cortical infarcts impaired an established unimanual reaching skill in the paretic forelimb, rats underwent a 7 week period of de novo bimanual training (BiT) or no-training control procedures (Cont). Probes of paretic forelimb unimanual performance revealed significant improvements during and after the training period in BiT vs. Cont. We additionally observed a striking change in the bimanual task strategy over training days: a switch from the paretic to the nonparetic forelimb for initiating reach-to-grasp sequences. This motivated another study to test whether rats that established the bimanual skill prior to the infarcts would similarly switch handedness, which they did not, though paretic paw use for manipulative movements diminished. These results indicate that unimanual function of the paretic side can be improved by novel bimanual skill practice, even when it involves compensatory reliance on the nonparetic hand. They further support the suitability of the Popcorn Retrieval Task for studying bimanual skill learning effects in rats.

Rehabilitative training system based on a ceiling rail for detecting the intended movement direction of a user.

BACKGROUND: Accurate detection of the intended movement direction of a patient plays an important role in the development of a training system for gait rehabilitation and enables to increase the effect of gait rehabilitation training. OBJECTIVE: This study investigated the detection of the intended movement of a user to operate a ceiling rail-based rehabilitative training system with accurate timing. METHODS: To detect the movement direction intention of a user, two potentiometers were used to measure the movement direction in the anterior, posterior, and left and right directions of the user when operating the driving motor of the rehabilitative training system. A simple test mock-up with two potentiometers was fabricated, and the experiments were conducted to determine the effect of the direction of movement on the measured values of potentiometers. A direction measurement algorithm was developed to control the driving motor of the rail-based gait rehabilitative training system. RESULTS: The intended movement direction of the user could be predicted for eight directions by combining the "positive value, 0, negative value" of each measured value of the two potentiometers. Further, the developed algorithm was effectively used to control the driving function to assist the walking, sitting-standing, and climbing up-down the step activities in daily life. CONCLUSIONS: The movement intention detection function for users developed in this paper can be used to effectively control a rehabilitative training system for patients with hemiplegia to improve gait movement and posture balance, thereby improving their function of activities of daily living.

Using the Principles of Multisensory Integration to Reverse Hemianopia.

Hemianopia can be rehabilitated by an auditory-visual "training" procedure, which restores visual responsiveness in midbrain neurons indirectly compromised by the cortical lesion and reinstates vision in contralesional space. Presumably, these rehabilitative changes are induced via mechanisms of multisensory integration/plasticity. If so, the paradigm should fail if the stimulus configurations violate the spatiotemporal principles that govern these midbrain processes. To test this possibility, hemianopic cats were provided spatially or temporally noncongruent auditory-visual training. Rehabilitation failed in all cases even after approximately twice the number of training trials normally required for recovery, and even after animals learned to approach the location of the undetected visual stimulus. When training was repeated with these stimuli in spatiotemporal concordance, hemianopia was resolved. The results identify the conditions needed to engage changes in remaining neural circuits required to support vision in the absence of visual cortex, and have implications for rehabilitative strategies in human patients.

Effect of Task-based Rehabilitation Training on Neural Circuit Plasticity and Forelimb Motor Function post Spinal Cord Injury in Mice / 中国康复理论与实践

Objective:To explore the effect of task-based rehabilitative training on neural circuit plasticity and forelimb motor function after C5 spinal cord injury in mice. Methods:A total of 21 healthy C57/BL mice were randomly and equally divided into sham group, model group and training group. The model was established by left C5 spinal cord crush injury. The lamina was removed without damaging the spinal cord in the sham group. Four weeks after injury, the training group received task-based rehabilitative training for four weeks. The horizontal ladder and rearing tests were used to assess motor function for forelimb before injury, and three days, two weeks, four weeks, six weeks and eight weeks after injury. The axons of the corticospinal tract in all mice were observed six weeks after injury by using biotinylated dextran amin (BDA) anterograde tracing. Eight weeks after injury, motor-evoked potential was applied to measure nerve conduction velocities in forelimb, while the axon sprouting and syntagmatic relation of neuron in the anterior horn of gray matter above lesion were observed by immunofluorescence double-labeling of BDA/neuron-specific nuclei protein (NeuN); the expression of Synapsin in the anterior horn of gray matter at lesion was observed by immunofluorescence double-labeling of NeuN/Synapsin I. Results:Eight weeks after injury, the latency of P1 and N1 was longer in the model group than in the sham group (P < 0.05), and was shorter in the training group than in the model group (P < 0.05). Compared with the sham group, the error rate of left forelimb increased, and the usage rate decreased (P < 0.05) in the model group and the training group; compared with the model group, the error rate of left forelimb decreased six weeks and eight weeks after injury (P < 0.05), and the usage rate increased eight weeks after injury (P < 0.05) in the treatment group. Compared with the model group, more axon sprouting co-localized with neurons in the anterior horn of gray matter above lesion (P < 0.05), and the expression of Synapsin I increased in the training group (P < 0.05). Conclusion:Task-based rehabilitative training could promote the neural circuit plasticity and improve the motor function of forelimb after spinal cord injury in mice.

Rehabilitative Training Interacts with Ischemia-Instigated Spine Dynamics to Promote a Lasting Population of New Synapses in Peri-Infarct Motor Cortex.

After subtotal infarcts of primary motor cortex (M1), motor rehabilitative training (RT) promotes improvements in paretic forelimb function that have been linked with its promotion of structural and functional reorganization of peri-infarct cortex, but how the reorganization unfolds is scantly understood. Cortical infarcts also instigate a prolonged period of dendritic spine turnover in peri-infarct cortex. Here we investigated the possibility that synaptic structural responses to RT in peri-infarct cortex reflect, in part, interactions with ischemia-instigated spine turnover. This was tested after artery-targeted photothrombotic M1 infarcts or Sham procedures in adult (4 months) C57BL/6 male and female GFP-M line (n = 24) and male yellow fluorescent protein-H line (n = 5) mice undergoing RT in skilled reaching or no-training control procedures. Regardless of training condition, spine turnover was increased out to 5 weeks postinfarct relative to Sham, as was the persistence of new spines formed within a week postinfarct. However, compared with no-training controls, new spines formed during postinfarct weeks 2-4 in mice undergoing RT persisted in much greater proportions to later time points, by a magnitude that predicted behavioral improvements in the RT group. These results indicate that RT interacts with ischemia-instigated spine turnover to promote preferential stabilization of newly formed spines, which is likely to yield a new population of mature synapses in peri-infarct cortex that could contribute to cortical functional reorganization and behavioral improvement. The findings newly implicate ischemia-instigated spine turnover as a mediator of cortical synaptic structural responses to RT and newly establish the experience dependency of new spine fates in the postischemic turnover context.SIGNIFICANCE STATEMENT Motor rehabilitation, the main treatment for motor impairments after stroke, is far from sufficient to normalize function. A better understanding of neural substrates of rehabilitation-induced behavioral improvements could be useful for understanding how to optimize it. Here, we investigated the nature and time course of synaptic responses to motor rehabilitative training in vivo Focal ischemia instigated a period of synapse turnover in peri-infarct motor cortex of mice. Rehabilitative training increased the stability of new synapses formed during the initial weeks after the infarct, the magnitude of which was correlated with improvements in skilled motor performance. Therefore, the maintenance of new synapses formed after ischemia could represent a structural mechanism of rehabilitative training efficacy.

Rehabilitative Training in Animal Models of Spinal Cord Injury.

Rehabilitative motor training is currently one of the most widely used approaches to promote moderate recovery following injuries of the central nervous system. Such training is generally applied in the clinical setting, whereas it is not standard in preclinical research. This is a concern as it is becoming increasingly apparent that neuroplasticity enhancing treatments require training or some form of activity as a co-therapy to promote functional recovery. Despite the importance of training and the many open questions regarding its mechanistic consequences, its use in preclinical animal models is rather limited. Here we review approaches, findings and challenges when training is applied in animal models of spinal cord injury, and we suggest recommendations to facilitate the integration of training using an appropriate study design, into pre-clinical studies.

Therapeutic Application of Transcranial Magnetic Stimulation Combined with Rehabilitative Training for Incomplete Spinal Cord Injury: A Case Report.

BACKGROUND: Only a few researchers have therapeutically applied transcranial magnetic stimulation (TMS) for patients with spinal cord injury. The purpose of this case study was to evaluate the safety, feasibility, and efficacy of therapeutic TMS combined with rehabilitative training for a patient with tetraparesis resulting from incomplete spinal cord injury. CASE: An 82-year-old male patient with incomplete spinal cord injury was admitted to our department for long-term rehabilitation. Eighteen days prior to admission, the patient sustained the injury in a fall. At admission to our department, the patient was diagnosed as having injury of the spinal cord at the C6 level. From the 76th day after admission, when the patient was considered to have attained a plateau state of recovery, application of therapeutic TMS was initiated using a double-cone coil. Two 15-min sessions of 10-Hz TMS were scheduled for daily application. Simultaneously, rehabilitative training was continuously provided. This patient received a total of 30 sessions of TMS over 19 days. Neither adverse effects nor deterioration of neurological symptoms was recognized during the intervention period. With this application of TMS, some improvements were evident in the American Spinal Injury Association motor score, the knee muscle strength, and the calf circumference. DISCUSSION: This case study demonstrated the safety and feasibility of TMS combined with rehabilitative training in a patient with incomplete spinal cord injury. Our protocol featuring TMS might constitute a novel neurorehabilitation intervention for such patients; however, the efficacy of the protocol should be confirmed in a large number of patients.

Axonal remodeling in the corticospinal tract after stroke: how does rehabilitative training modulate it?

Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.

Neural network remodeling underlying motor map reorganization induced by rehabilitative training after ischemic stroke.

Motor map reorganization is believed to be one mechanism underlying rehabilitation-induced functional recovery. Although the ipsilesional secondary motor area has been known to reorganize motor maps and contribute to rehabilitation-induced functional recovery, it is unknown how the secondary motor area is reorganized by rehabilitative training. In the present study, using skilled forelimb reaching tasks, we investigated neural network remodeling in the rat rostral forelimb area (RFA) of the secondary motor area during 4weeks of rehabilitative training. Following photothrombotic stroke in the caudal forelimb area (CFA), rehabilitative training led to task-specific recovery and motor map reorganization in the RFA. A second injury to the RFA resulted in reappearance of motor deficits. Further, when both the CFA and RFA were destroyed simultaneously, rehabilitative training no longer improved task-specific recovery. In neural tracer studies, although rehabilitative training did not alter neural projection to the RFA from other brain areas, rehabilitative training increased neural projection from the RFA to the lower spinal cord, which innervates the muscles in the forelimb. Double retrograde tracer studies revealed that rehabilitative training increased the neurons projecting from the RFA to both the upper cervical cord, which innervates the muscles in the neck, trunk, and part of the proximal forelimb, and the lower cervical cord. These results suggest that neurons projecting to the upper cervical cord provide new connections to the denervated forelimb area of the spinal cord, and these new connections may contribute to rehabilitation-induced task-specific recovery and motor map reorganization in the secondary motor area.

Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury.

There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. This article is part of a Special Issue entitled SI:Brain injury and recovery.

cAMP/PKA-pCREB signal transduction pathway may mediate a promoting effect of rehabilitation training on motor function after ischemic stroke in rats / 中国实验动物学报

Objective To explore whether the cAMP-PKA-pCREB signal pathway plays a role in promoting the recovery of motor function after rehabilitation training in cerebral ischemia-reperfusion rats .Methods The middle cerebral artery occlusion model ( MCAO) was established by modified Longa nylon occlusion method in adult male Sprague -Dawley rats.The 84 MCAO rats were selected and randomly assigned to four groups:the natural recovery group without any special training (group B, n=24),natural recovery group with Rp-cAMP (group C, n=24), rehabilitation training group (group D, n=18) and rehabilitation training with Rp-cAMP (group E, n=18), and in addition a control group (group A, n =12).To establish rat MCAO models immediately after injection of Rp-cAMP into the lateral ventricle of the brain .The rats in the groups D and E were trained by balance beam , bar rotating and rolling exercises started at 48 h after MCAO.The ex-pression of PKA was determined by enzyme-linked immunosorbent assay ( ELISA) and the pCREB protein expression was detected by Western blot assay .Motor function was assessed by balance beam test .Results (1) The motor function score in the group C was significantly higher than that of group B , suggesting that Rp-cAMP inhibited the recovery of motor func-tion in the cerebral ischemia-reperfusion rats .The score of group D was significantly lower than that of groups B and E , in-dicating that Rp-cAMP inhibited the promoting effect of rehabilitation training on motor function in the cerebral ischemia -reperfusion rats.(2) The expressions of PKA and pCREB proteins detected at 2nd, 7th, 14th, and 21th days after surgery showed that their expressions in the group D were significantly higher than those of the groups B and E , indicating that re-habilitation training promoted the expression of PKA and pCREB , and Rp-cAMP significantly inhibited the promoting effect of rehabilitation training on the expressions of PKA and pCREB proteins .Conclusion cAMP/PKA-pCREB signal trans-duction pathway may mediate a promoting effect of rehabilitation training on the recovery of motor function after ischemic stroke in rats.

Effects of two rehabilitative therapies on cardiac rehabilitation of patients with acute myocardial infarction after interventional program / 现代临床护理

Objective To compare the different effects of two rehabilitative therapies on cardiac rehabilitation of patients with acute myocardial infarction after interventional program.Methods Eighty AMI patients with no complications after interventional treatment were randomized equally into the observation group and the control group.The patients in the control group were given two-week cardiac rehabilitative training in line with the clinical nursing pathway.Besides the treatment in the control group,those in the observation group were given 10-day cardiac rehabilitative training by optimizing the nursing pathway.The two groups were compared in terms of left ventricular ejection fraction,self-care ability,heart function grading,incidence of complications,hospital stay and hospitalization cost.Results At discharge,The observation group was significantly better than the control group in terms of left ventricular ejection fraction,self-care ability and grading of cardiac function(all P<0.05).In regard to the incidence of complications,there was no statistically significant difference between the groups.Hospital stay in the observation group was obviously shorter than that in the control group and the hospitalization cost significantly less than that in the control group(P<0.01).Conclusion The 10-day cardiac rehabilitation program can promote patients’recovery,shorten the hospital stay and reduce the medical expense.