Neurorehabilitation and Neural Repair current issue

ASNR/WFNR News

Tue, 27 Oct 2009 11:29:16 PDT

Aerobic Exercise Improves Cognition and Motor Function Poststroke

Tue, 27 Oct 2009 11:29:16 PDT

Background. Cognitive deficits impede stroke recovery. Aerobic exercise (AEX) improves cognitive executive function (EF) processes in healthy individuals, although the learning benefits after stroke are unknown. Objective. To understand AEX-induced improvements in EF, motor learning, and mobility poststroke. Methods. Following cardiorespiratory testing, 38 chronic stroke survivors were randomized to 2 different groups that exercised 3 times a week (45-minute sessions) for 8 weeks. The AEX group (n = 19; 9 women; 10 men; 64.10 ± 12.30 years) performed progressive resistive stationary bicycle training at 70% maximal heart rate, whereas the Stretching Exercise (SE) group (n = 19; 12 women; 7 men; 58.96 ± 14.68 years) performed stretches at home. Between-group comparisons were performed on the change in performance at "Post" and "Retention" (8 weeks later) for neuropsychological and motor function measures. Results. VO₂max significantly improved at Post with AEX (P = .04). AEX also improved motor learning in the less-affected hand, with large effect sizes (Cohen’s d calculation). Specifically, AEX significantly improved information processing speed on the serial reaction time task (SRTT; ie, "procedural motor learning") compared with the SE group at Post (P = .024), but not at Retention. Also, at Post (P = .038), AEX significantly improved predictive force accuracy for a precision grip task requiring attention and conditional motor learning of visual cues. Ambulation and sit-to-stand transfers were significantly faster in the AEX group at Post (P = .038), with balance control significantly improved at Retention (P = .041). EF measurements were not significantly different for the AEX group. Conclusion. AEX improved mobility and selected cognitive domains related to motor learning, which enhances sensorimotor control after stroke.

The Effects of Repeated Rehabilitation "Tune-Ups" on Functional Recovery After Focal Ischemia in Rats

Clarke, J., Mala, H., Windle, V., Chernenko, G., Corbett, D. — Tue, 27 Oct 2009 11:29:16 PDT

Background. For most stroke survivors, rehabilitation therapy is the only treatment option available. The beneficial effects of early rehabilitation on neuroplasticity and functional recovery have been modeled in experimental stroke using a combination of enriched environment and rehabilitation. However, the impact of a secondary intervention, such as a periodic return to therapy, remains unclear. Objective. This study examines whether a return to enriched rehabilitation (ie, "tune-up") can further promote functional recovery or produce beneficial changes in brain plasticity in the chronic phase of stroke recovery. Methods. Rats were exposed to focal ischemia (endothelin-1 applied to forelimb sensorimotor cortex and dorsolateral striatum) and allowed to recover either in standard housing or in a combination of enriched environment and rehabilitative reaching for 9 weeks. Animals were then exposed to rotating periods of standard housing (5 weeks) and intensive "tune-up" therapy consisting of various sensorimotor/cognitive activities (2 weeks). Functional recovery was assessed using the Montoya staircase, beam-traversing, and cylinder tests, and Golgi—Cox analysis was used to examine dendritic complexity in the contralesional forelimb motor cortex. Results. Although early enriched rehabilitation significantly improved sensorimotor function in both the beam and staircase tests, "tune-up" therapy had no effect on recovery. Golgi—Cox analysis revealed no effect of treatment on dendritic complexity. Conclusions. This study reaffirms the benefits of early rehabilitation for functional recovery after stroke. However, "tune-up" therapy provided no benefit in ischemic animals regardless of earlier rehabilitation experience. It is possible that alternative approaches in the chronic phase may prove more effective.

The Neural Stem Cell Line CTX0E03 Promotes Behavioral Recovery and Endogenous Neurogenesis After Experimental Stroke in a Dose-Dependent Fashion

Stroemer, P., Patel, S., Hope, A., Oliveira, C., Pollock, K., Sinden, J. — Tue, 27 Oct 2009 11:29:16 PDT

Background. This study investigated behavioral recovery in rats following implanting increasing doses of CTX0E03 cells into the putamen ipsilateral to the stroke damage. Postmortem histological analysis investigated possible mechanisms of behavioral recovery. Methods. At 4 weeks after middle cerebral artery occlusion (MCAO), rats were treated with 4500, 45 000, or 450 000 CTX0E03 cells or vehicle implanted into the putamen with testing on a battery of tasks preocclusion and postocclusion. Histological examination of brains included assessment of lesion volumes, implant cell survival and differentiation, changes to host brain matrix, angiogenesis, and neurogenesis using immunohistochemical methods. Results. Statistically significant dose-related recovery in sensorimotor function deficits (bilateral asymmetry test [BAT; P < .0002] in the mid- and high-dose groups and rotameter test after amphetamine exposure [P < .05] in the high-dose group) was found in the CTX0E03 cell implanted groups compared to the vehicle group. In-life functional improvements correlated with cell dose, though did not correlate with survival of CTX0E03 cells measured at postmortem. Surviving CTX0E03 cells differentiated into oligodendroglial and endothelial phenotypes. MCAO-induced reduction of neurogenesis in the subventricular zone (SVZ) was partially restored to that observed in sham operated controls. No adverse CTX0E03 cell-related effects were observed during in-life observations or on tissue histology. Conclusions. This study found that the implantation of CTX0E03 human neural stem cells in rats after MCAO stroke promoted significant behavioral recovery depending on cell dose. The authors propose a paracrine trophic mechanism, which is triggered early after CTX0E03 cell implantation, and which in turn targets restoration of neurogenesis in the SVZ of MCAO rats.

Effect of Treadmill Training on Autonomic Dysreflexia in Spinal Cord--Injured Rats

Laird, A. S., Carrive, P., Waite, P. M. E. — Tue, 27 Oct 2009 11:29:16 PDT

Background. Weight-supported treadmill training is an emerging rehabilitation method used to improve locomotor ability in patients with spinal cord injury (SCI). However, little research has been undertaken to test the effect of such training on other consequences of SCI, such as neuropathic pain and autonomic dysfunction. Objective. This study investigates the effects of chronic treadmill training on the development of autonomic dysreflexia (AD), a form of cardiovascular dysfunction common in patients with cervical or high thoracic injury. Methods. Treadmill training commenced in adult male rats (n = 11) 3 days following complete T4 transection, whereas a sedentary SCI group (n = 9) and an intact group (n = 6) had no intervention. Treadmill training (up to 0.4 m/s) lasted for 10 min/d 5 days a week, for 6 weeks. Weekly measurements of locomotor ability (BBB scale), baseline mean arterial pressure, and heart rate were made, as were cardiovascular responses to training and colorectal distension (to trigger AD). Results. Treadmill training improved BBB scores from 2 weeks post-transection onward (P = .010). However, it increased AD, resulting in augmented pressor responses from 2 to 6 weeks post-transection (P = .029). Comparison of the vascular response to phenylephrine under ganglionic blockade showed an enhanced vasoconstrictor response in the renal vasculature of trained SCI animals. Immunohistochemical comparison of the L1—L6 spinal cord segments showed an increased area of CGRP immunoreactivity in the dorsal horn (lamina III/IV) of treadmill-trained SCI compared with intact and sedentary SCI animals. Conclusions. These results suggest that treadmill training exaggerated AD responses perhaps through a combination of enhanced vascular reactivity and central plasticity.

Brainstem Reflexes Are Enhanced Following Severe Spinal Cord Injury and Reduced by Continuous Intrathecal Baclofen

Kumru, H., Kofler, M., Valls-Sole, J., Portell, E., Vidal, J. — Tue, 27 Oct 2009 11:29:16 PDT

Objective. Plastic changes in the human central nervous system can occur at multiple levels, including circuits rostral to the lesion level in spinal cord injury (SCI). GABA is the most important inhibitory neurotransmitter in the brain. The authors hypothesized that one of the consequences of plasticity in SCI patients could be enhancement of brainstem reflexes, and they investigated the effect of continuous intrathecal baclofen (CITB) on such enhancement. Methods. The authors studied the early ipsilateral component R1 and the late component R2 of the blink reflex (BR), jaw jerk, masseter silent period (MSP), and auditory startle response (ASR) in 9 SCI patients without baclofen and in 8 with CITB. Nine healthy volunteers served as controls. Results. The amplitude of R1 of BR was significantly smaller in patients with CITB than in the other groups. The area of R2 of BR and of the ASR recorded in the orbicularis oculi, sternocleidomastoid, and biceps brachii muscles were significantly larger in SCI patients without baclofen than in controls, whereas there was no difference between patients with CITB and controls. The MSP magnitude was significantly larger in patients with CITB as compared with those without baclofen. Conclusion. The enhancement of brainstem reflexes in SCI patients may be due to plastic changes at the brainstem level after SCI. The significant reduction in response size in patients with CITB in comparison with patients without baclofen suggests that the enhancement of brainstem reflexes may be due to decreased GABAergic activity and that CITB is effective in reducing abnormal brainstem hyperexcitability.

Repeated Maximal Volitional Effort Contractions in Human Spinal Cord Injury: Initial Torque Increases and Reduced Fatigue

Hornby, T. G., Lewek, M. D., Thompson, C. K., Heitz, R. — Tue, 27 Oct 2009 11:29:17 PDT

Background. Substantial data indicate greater muscle fatigue in individuals with spinal cord injury (SCI) compared with healthy control subjects when tested by using electrical stimulation protocols. Few studies have investigated the extent of volitional fatigue in motor incomplete SCI. Methods. Repeated, maximal volitional effort (MVE) isometric contractions of the knee extensors (KE) were performed in 14 subjects with a motor incomplete SCI and in 10 intact subjects. Subjects performed 20 repeated, intermittent MVEs (5 seconds contraction/5 seconds rest) with KE torques and thigh electromyographic (EMG) activity recorded. Results. Peak KE torques declined to 64% of baseline MVEs with repeated efforts in control subjects. Conversely, subjects with SCI increased peak torques during the first 5 contractions by 15%, with little evidence of fatigue after 20 repeated efforts. Increases in peak KE torques and the rate of torque increase during the first 5 contractions were attributed primarily to increases in quadriceps EMG activity, but not to decreased knee flexor co-activation. The observed initial increases in peak torque were dependent on the subject’s volitional activation and were consistent on the same or different days, indicating little contribution of learning or accommodation to the testing conditions. Sustained MVEs did not elicit substantial increases in peak KE torques as compared to repeated intermittent efforts. Conclusions. These data revealed a marked divergence from expected results of increased fatigability in subjects with SCI, and may be a result of complex interactions between mechanisms underlying spastic motor activity and changes in intrinsic motoneuron properties.

Subjective Fatigue, Mental Effort, and Attention Deficits After Severe Traumatic Brain Injury

Belmont, A., Agar, N., Azouvi, P. — Tue, 27 Oct 2009 11:29:17 PDT

Objective. Although fatigue is one of the most frequent complaints of individuals with traumatic brain injury (TBI), its mechanisms remain poorly understood. The objective of this study was to assess the relationships between subjective mental fatigue, mental effort, attention deficits, and mood after severe TBI. Methods and participants. A total of 27 patients with subacute/chronic severe TBI were compared with matched controls. Patients first rated their baseline subjective fatigue on the Fatigue Severity Scale (FSS) and on the Visual Analog Scale for Fatigue (VAS-F). Mood was assessed with the Montgomery and Asberg Depression Rating Scale (MADRS). Then, they performed a long-duration selective attention task, separated in 2 parts. Fatigue on the VAS-F was assessed again between the 2 parts and at the end of the attention task. Patients were also asked to rate on the VAS the level of subjective mental effort devoted to the task. Results. Patients reported a higher baseline fatigue than controls. They performed significantly poorer on the selective attention task. Significant correlations were found in the group with TBI between attention performance, mental effort, and subjective fatigue. Depression did not significantly correlate with fatigue. Discussion and conclusions. These findings suggest that patients with more severe attention deficits have to produce higher levels of mental effort to manage a complex task, which may increase subjective fatigue, in line with the coping hypothesis.

Comparison of Bilateral and Unilateral Training for Upper Extremity Hemiparesis in Stroke

Stoykov, M. E., Lewis, G. N., Corcos, D. M. — Tue, 27 Oct 2009 11:29:17 PDT

Background. Upper extremity hemiparesis is the most common poststroke disability. Longitudinal studies have indicated that 30% to 66% of stroke survivors do not have full arm function 6 months poststroke. One promising treatment approach is bilateral training. To date, no randomized, blinded study of efficacy comparing 2 groups (bilateral training vs unilateral training) using analogous tasks has been performed in chronic stroke survivors with moderate upper extremity impairment. Objective. To compare the effectiveness of bilateral training with unilateral training for individuals with moderate upper limb hemiparesis. The authors hypothesized that bilateral training would be superior to unilateral training in the proximal extremity but not the distal one. Methods. Twenty-four subjects participated in a randomized, single-blind training study. Subjects in the bilateral group (n = 12) practiced bilateral symmetrical activities, whereas the unilateral group (n = 12) performed the same activity with the affected arm only. The activities consisted of reaching-based tasks that were both rhythmic and discrete. The Motor Assessment Scale (MAS), Motor Status Scale (MSS), and muscle strength were used as outcome measures. Assessments were administered at baseline and posttraining by a rater blinded to group assignment. Results. Both groups had significant improvements on the MSS and measures of strength. The bilateral group had significantly greater improvement on the Upper Arm Function scale (a subscale of the MAS-Upper Limb Items). Conclusion. Both bilateral and unilateral training are efficacious for moderately impaired chronic stroke survivors. Bilateral training may be more advantageous for proximal arm function.

13th International Symposium on Neural Regeneration (ISNR)

Tue, 27 Oct 2009 11:29:17 PDT