Xiaolin Huang

Repetitive transcranial magnetic stimulation promotes neural stem cell proliferation via the regulation of MiR-25 in a rat model of focal cerebral ischemia.

Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.

Electroacupuncture Ameliorates Learning and Memory via Activation of the CREB Signaling Pathway in the Hippocampus to Attenuate Apoptosis after Cerebral Hypoperfusion

Studies have shown that electroacupuncture (EA) ameliorates learning and memory after ischemic injury. However, there have been few studies elucidating the mechanisms of EA on learning and memory in cerebral hypoperfusion. In this study, we explored the cAMP response element-binding protein (CREB) signaling pathway-mediated antiapoptotic action involved in EA-induced improvement of learning and memory. EA at GV20 and GV14 acupoints was applied in cerebral hypoperfusion rats. A Morris water maze task was performed, and the immunoreactivities of pCREB, Bcl-2, and Bax in the hippocampal CA1 area were evaluated by the Western blotting technique. Our findings indicated that (1) EA ameliorated spatial learning and memory impairment in cerebral hypoperfusion rats; (2) EA increased the immunoreactivities of pCREB and Bcl-2 and decreased the immunoreactivity of Bax; (3) intracerebroventricular administration of H89 (the inhibitor of protein kinase A) blocked EA-induced, pCREB-mediated antiapoptotic action and improved learning and memory. These results suggest that EA can ameliorate learning and memory via activation of the CREB signaling pathway in the hippocampus to attenuate apoptosis after cerebral hypoperfusion.

The neuronal correlates of mirror therapy: A functional magnetic resonance imaging study on mirror-induced visual illusions of ankle movements

Recovery in stroke is mediated by neural plasticity. Mirror therapy is an effective method in the rehabilitation of stroke patients, but the mechanism is still obscure. To identify the neural networks associated with the effect of lower-limbs mirror therapy, we investigated a functional magnetic resonance imaging (fMRI) study of mirror-induced visual illusion of ankle movements. Five healthy controls and five left hemiplegic stroke patients performed tasks related to mirror therapy in the fMRI study. Neural activation was compared in a no-mirror condition and a mirror condition. All subjects in the experiment performed the task of flexing and extending the right ankle. In a mirror condition, movement of the left ankle was simulated by mirror reflection of right ankle movement. Changes in neural activation in response to mirror therapy were assessed both in healthy controls and stroke patients. We found strong activation of the motor cortex bilaterally in healthy controls, as well as significant activation of the ipsilateral sensorimotor cortex, the occipital gyrus, and the anterior prefrontal gyrus in stroke patients with respect to the non-mirror condition. We concluded that mirror therapy of ankle movements may induce neural activation of the ipsilesional sensorimotor cortex, and that cortical reorganization may be useful for motor rehabilitation in stroke.

A study of astrocyte activation in the periinfarct region after cerebral ischemia with electroacupuncture

Objective: To investigate the effects of electroacupuncture (EA) on the activation of astrocytes (AST) in the periinfarct region after cerebral ischemia, as well as to evaluate potential behavioural improvement after EA treatment. Methods: Male Wistar rats were randomly divided into normal, model and EA groups. Rats in each group were further divided into 7, 14 and 28 days sub-groups. A model of middle cerebral artery occlusion was established, followed by 7, 14 or 28 days of EA on ‘Bai hui’ and ‘Da zhui’ acupoints. The number of GFAP-immunoreactive cells was determined and behavioural tests were performed. Results: Many more GFAP-immunoreactive cells were detected in the EA group on day 14 than on day 7 after ischemia and a slightly decreased number of immunoreactive cells were observed on day 28. The results of behavioural tests of animals in the EA group on the beam balance performance and prehensile traction performance were superior to that of animals in the model group. Conclusion: These findings indicate that EA has the potential to activate AST in the periinfarct region and to avoid excess reactive gliosis and also can facilitate the recovery of post-ischemic behavioural dysfunction.

Biomechanical Characteristics of Hand Coordination in Grasping Activities of Daily Living

Hand coordination can allow humans to have dexterous control with many degrees of freedom to perform various tasks in daily living. An important contributing factor to this important ability is the complex biomechanical architecture of the human hand. However, drawing a clear functional link between biomechanical architecture and hand coordination is challenging. It is not understood which biomechanical characteristics are responsible for hand coordination and what specific effect each biomechanical characteristic has. To explore this link, we first inspected the characteristics of hand coordination during daily tasks through a statistical analysis of the kinematic data, which were collected from thirty right-handed subjects during a multitude of grasping tasks. Then, the functional link between biomechanical architecture and hand coordination was drawn by establishing the clear corresponding causality between the tendinous connective characteristics of the human hand and the coordinated characteristics during daily grasping activities. The explicit functional link indicates that the biomechanical characteristic of tendinous connective architecture between muscles and articulations is the proper design by the Creator to perform a multitude of daily tasks in a comfortable way. The clear link between the structure and the function of the human hand also suggests that the design of a multifunctional robotic hand should be able to better imitate such basic architecture.

Electroacupuncture Ameliorates Learning and Memory and Improves Synaptic Plasticity via Activation of the PKA/CREB Signaling Pathway in Cerebral Hypoperfusion

Electroacupuncture (EA) has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are ill-understood. The present study was undertaken to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following EA and to investigate the role of PKA/CREB pathway. We used a rat 2-vessel occlusion (2VO) model and delivered EA at Baihui (GV20) and Dazhui (GV14) acupoints. Morris water maze (MWM) task, electrophysiological recording, Golgi silver stain, Nissl stain, Western blot, and real-time PCR were employed. EA significantly (1) ameliorated the spatial learning and memory deficits, (2) alleviated long-term potentiation (LTP) impairment and the reduction of dendritic spine density, (3) suppressed the decline of phospho-CREB (pCREB) protein, brain-derived neurotrophic factor (BDNF) protein, and microRNA132 (miR132), and (4) reduced the increase of p250GAP protein of 2VO rats. These changes were partially blocked by a selective protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89), suggesting that the PKA/CREB pathway is potentially involved in the effects of EA. Moreover, any significant damage to the pyramidal cell layer of CA1 subregion was absent. These results demonstrated that EA could ameliorate learning and memory deficits and alleviate hippocampal synaptic plasticity impairment of cerebral hypoperfusion rats, potentially mediated by PKA/CREB signaling pathway.

Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Impairment by Enhancing Neurogenesis and Suppressing Apoptosis in the Hippocampus in Rats with Ischemic Stroke

Cognitive impairment is a serious mental deficit caused by stroke that can severely affect the quality of a survivors life. Repetitive transcranial magnetic stimulation (rTMS) is a well-known rehabilitation modality that has been reported to exert neuroprotective effects after cerebral ischemic injury. In the present study, we evaluated the therapeutic efficacy of rTMS against post-stroke cognitive impairment (PSCI) and investigated the mechanisms underlying its effects in a middle cerebral artery occlusion (MCAO) rat model. The results showed that rTMS ameliorated cognitive deficits and tended to reduce the sizes of cerebral lesions. In addition, rTMS significantly improved cognitive function via a mechanism involving increased neurogenesis and decreased apoptosis in the ipsilateral hippocampus. Moreover, brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), were clearly upregulated in ischemic hippocampi after treatment with rTMS. Additionally, further studies demonstrated that rTMS markedly enhanced the expression of the apoptosis-related B cell lymphoma/leukemia gene 2 (Bcl-2) and decreased the expression of the Bcl-2-associated protein X (Bax) and the number of TUNEL-positive cells in the ischemic hippocampus. Both protein levels and mRNA levels were investigated. Our findings suggest that after ischemic stroke, treatment with rTMS promoted the functional recovery of cognitive impairments by inhibiting apoptosis and enhancing neurogenesis in the hippocampus and that this mechanism might be mediated by the BDNF signaling pathway.

Effects of mirror therapy combined with neuromuscular electrical stimulation on motor recovery of lower limbs and walking ability of patients with stroke: a randomized controlled study:

Objective: To investigate the effectiveness of mirror therapy combined with neuromuscular electrical stimulation in promoting motor recovery of the lower limbs and walking ability in patients suffering from foot drop after stroke. Design: Randomized controlled study. Setting: Inpatient rehabilitation center of a teaching hospital. Subjects: Sixty-nine patients with foot drop. Intervention: Patients were randomly divided into three groups: control, mirror therapy, and mirror therapy + neuromuscular electrical stimulation. All groups received interventions for 0.5 hours/day and five days/week for four weeks. Main measures: 10-Meter walk test, Brunnstrom stage of motor recovery of the lower limbs, Modified Ashworth Scale score of plantar flexor spasticity, and passive ankle joint dorsiflexion range of motion were assessed before and after the four-week period. Results: After four weeks of intervention, Brunnstrom stage (P = 0.04), 10-meter walk test (P < 0.05), and passive range of motion (P < 0.05) showed obvious improvements between patients in the mirror therapy and control groups. Patients in the mirror therapy + neuromuscular electrical stimulation group showed better results than those in the mirror therapy group in the 10-meter walk test (P < 0.05). There was no significant difference in spasticity between patients in the two intervention groups. However, compared with patients in the control group, patients in the mirror therapy + neuromuscular electrical stimulation group showed a significant decrease in spasticity (P < 0.001). Conclusion: Therapy combining mirror therapy and neuromuscular electrical stimulation may help improve walking ability and reduce spasticity in stroke patients with foot drop.

Poster 336: A Pilot Study of a Combined Traction and Mobilization Device for Cervical Spinal Rehabilitation

Disclosures: L. M. Huddleston, None Patients or Programs: A 14-year-old girl with heel fracture. Program Description: A 14-year-old girl presented to a podiatrist with left foot pain after participating in recreational activities. Radiographs showed a heel fracture. She was casted. After cast removal, she complained of persistent left medial ankle and foot pain. She was diagnosed with tarsal tunnel syndrome. MRI showed fibrosis of the plantar fascia. She was referred for an electrodiagnostic evaluation for tarsal tunnel syndrome. Setting: Outpatient physiatry clinic. Results: Physical examination revealed poorly defined lower extremity musculature, 3 /5 strength on left dorsi and plantar flexion, and mild tenderness of the left medial ankle. Light touch sensation was diminished over the left medial ankle and left great toe. Motor nerve conduction studies in the leg and arm revealed prolonged distal latencies and diminished CMAPs. All condition velocities were 25 ms. F latencies in median, peroneal, and tibial nerves were prolonged. Needle examination revealed decreased motor unit recruitment. Further history revealed that the patient had difficulty keeping up with her peers in recreational activities. She also reported frequent tripping and falling that began around the age of 7. The patient’s mother denied any family history of neuromuscular disease. Based on the patient’s history, examination findings, and electrodiagnostic study results, she was diagnosed with Charcot-Marie-Tooth disease type I (CMT I). The findings were discussed with the patient and her mother, and follow-up with a neurologist was recommended. Discussion: CMT is the most common form of hereditary neuropathy. CMT I usually manifests in the first to third decades, although patients may remain asymptomatic until much later in life. During childhood, patients may have difficulty running and keeping up with their peers. Case reports of upper extremity fracture in CMT have been documented, but a general literature search revealed no heel fractures as the presenting sign of CMT. Conclusions: Patients with CMT may not present with classic history and physical examination findings. This case stresses the importance of further physical examination, history taking, and appropriate diagnostic testing in children with traumatic injuries.

Poster 391: Electroacupuncture Combined with Repetitive Transcranial Magnetic Stimulation Enhance Learning and Memory and Improve Synaptic Ultrastructure after Cerebral Ischemia

Disclosures: S. Chandran, None. Patients or Programs: A 44-year-old woman with a right basal ganglia hemorrhagic stroke and severe spastic left hemiparesis. Program Description: She presented with severe left spastic hypertonia impeding activities of daily living, ambulation and rehabilitation progress. Modified Ashworth scale (MAS) scores were: 3 for elbow extensors, wrist flexors, wrist extensors, and ankle dorsiflexors, 2 for elbow flexors and 1 for knee extensors. She required moderate assistance for toileting, and maximum assistance for bed mobility and transfers. She also noted painful spasms, difficulty advancing her left leg and poor hand hygiene. Setting: Comprehensive Inpatient Rehabilitation Unit. Results: Multiple courses of antispasmodics failed due to drug intolerance and lack of response. Botulinum toxin injections were also unsuccessful. At 9 weeks post stroke, she underwent a successful intrathecal baclofen pump (ITB) screening trial, followed by ITB pump implantation at 49.96 g/mL/day. Transient postoperative spinal headache and nausea resolved followed by marked overall improvement; in 2 weeks, she was supervision for transfers, minimum assistance for toileting, and ambulating using a hemi bar with contact guard. She had improved left active knee extension and knee flexion during swing. At 2 months, she continued to make functional gains, ambulating at modified independence, with reduced tone in affected muscle groups. Discussion: Post stroke spastic hypertonia can cause significant impairments and disability. Oral medications and physical modalities are not universally tolerable or effective. ITB with direct infusion to the intrathecal space utilizes a programmable pump, minimizing systemic side effects. Conventional pump implantation occurs 3 to 6 months post stroke due to concerns of impaired cognitive and motor recovery. There are few documented cases of successful early ITB placement. Patients with severe spasticity impacting rehabilitation progress, positioning, comfort and hygiene may benefit from early ITB placement. Conclusions: In a selected case, early ITB placement benefited rehabilitation without impeding cognitive or motor recovery.