Functional electrical stimulation post-spinal cord injury improves locomotion and increases afferent input into the central nervous system in rats.

BACKGROUND: Functional electrical stimulation (FES) has been found to be effective in restoring voluntary functions after spinal cord injury (SCI) and stroke. However, the central nervous system (CNS) changes that occur in as a result of this therapy are largely unknown. OBJECTIVE: To examine the effects of FES on the restoration of voluntary locomotor function of the CNS in a SCI rat model. METHODS: SCI rats were instrumented with chronic FES electrodes in the hindlimb muscles and were divided into two groups: (a) FES therapy and (b) sedentary. At day 7 post-SCI, the animals were assessed for locomotion performance by using a Basso, Beattie and Bresnahan (BBB) scale. They were then anesthetized for a terminal in vivo experiment. The lumbar spinal cord and somatosensory cortex were exposed and the instrumented muscles were stimulated electrically. Associated neurovascular responses in the CNS were recorded with an intrinsic optical imaging system. RESULTS: FES greatly improved locomotion recovery by day 7 post-SCI, as measured by BBB scores (P < 0.05): (a) FES 10 ± 2 and (b) controls 3 ± 1. Furthermore, the FES group showed a significant increase (P < 0.05) of neurovascular activation in the spinal cord and somatosensory cortex when the muscles were stimulated between 1 and 3 motor threshold (MT). CONCLUSION: Hind limb rehabilitation with FES is an effective strategy to improve locomotion during the acute phase post-SCI. The results of this study indicate that after FES, the CNS preserves/acquires the capacity to respond to peripheral electrical stimulation.

Laminar optical tomography of the hemodynamic response in the lumbar spinal cord of rats.

Intrinsic optical imaging (IOI) has emerged as a very powerful tool to assess neuronal function in small animals. Although it has been used extensively in the brain, its application to the spinal cord is rare. The inability of intrinsic optical techniques to resolve different depths and embedded gray matter hampers their capacity to distinguish larger vasculature contributions of hemodynamic signals originating from motoneuron and interneuron activation. Laminar optical tomography (LOT) is a recently-developed method that fills the gap left between IOI and diffuse optical imaging. With distinct source-detector separations, light that propagates deeper into tissues can be distinguished from light originating from the surface, providing depth sensitivity. In this work, LOT is investigated for the first time to image spinal cord activation with simultaneous IOI of the cortex in rats. Such proof of concept provides a powerful imaging modality to study spinal cord activation and disruption after injury.

Multimodal study of the hemodynamic response to hypercapnia in anesthetized aged rats.

With aging, the brain undergoes changes in metabolism and perfusion, both of which influence the widely used blood-oxygenation-level-dependent (BOLD) MRI signal. To isolate the vascular effects associated with age, this study measured the response to a hypercapnic challenge using different imaging modalities in 19 young (3 months-old) and 13 old (24 months-old) Long-Evans rats. Intrinsic optical imaging was used to measure oxy (HbO), deoxy (HbR) and total (HbT) hemoglobin concentration changes, laser speckle for cerebral blood flow (CBF) changes, and MRI for the BOLD signal. Older rats had smaller HbO (41% smaller), HbT (50%) and CBF (34%) responses, but the temporal dynamics did not exhibit significant age differences. The ratio of CBV to CBF responses was also smaller in older adults, potentially indicating a change in the compliance of vessels.

Aging-related differences in cerebral capillary blood flow in anesthetized rats.

Age-related decreases in baseline cerebral blood flow have been measured with various imaging modalities, however, the contribution of capillary flow to this phenomenon remain to elucidate. This study used 2-photon laser scanning fluorescence microscopy to measure capillary diameter, red blood cell speed, and flux in individual capillaries in the sensory-motor cortex of 12 adult (3-month-old) and 12 old (24-month-old) male Long-Evans rats under isoflurane anesthesia. The average (± standard deviation) diameter and speed over 921 capillaries were 6.4 ± 1.4 µm and 1.3 ± 1.1 mm/s, respectively. Red blood cell speed and flux were significantly higher, by 48% and 15%, respectively, in old compared with young animals (p < 5%). The diameter also showed a similar tendency (7% higher, p = 5.7%). Furthermore, capillary hematocrit and density were significantly lower in the older group (p < 5%), by 32% and 20%, respectively.

Characterization of the hemodynamic response in the rat lumbar spinal cord using intrinsic optical imaging and laser speckle.

Quantifying spinal cord functions is crucial for understanding neurophysiological mechanisms governing the intact and the injured spinal cord. Intrinsic optical imaging (IOI) and laser speckle provides measures of deoxyhemoglobin (HbR) and oxyhemoglobin (HbO(2)) concentrations, blood volume (BV) and blood flow (BF) at high spatial and temporal resolution. In this study we used IOI and laser speckle to characterize the hemodynamic response to neuronal activation in the lumbar spinal cord of anaesthetized rats (N=9). We report consistent temporal variations of HbR, HbO(2), BV and BF located ipsilaterally at L3-L5. Responses were significantly higher when stimulation intensity was increased. Vascular changes extended several millimetres from the epicenter, supporting the venous drainage observed in functional magnetic resonance imaging studies.

Optical imaging of vascular and metabolic responses in the lumbar spinal cord after T10 transection in rats.

Neuronal and vascular reorganization after spinal cord injury (SCI) is scarcely known although its characterization has major implications in understanding the functioning of the altered spinal cord. Several electrophysiological and anatomical lines of evidence support plasticity caudal to the lesion site, but do not provide sufficient clues about neuronal and vascular reorganization after SCI. The aim of the present study was to compare neuronal activation in the lumbar spinal cord between uninjured and SCI rats with novel optical imaging technology. The results showed significant haemodynamic response differences after sciatic nerve stimulation in uninjured controls, in comparison to SCI rats. Both timing and shape of the response were modified. In uninjured rats, blood flow presented an initial dip but was rapidly drained from the activation site through the venous system. In comparison, the blood transfer rate in SCI rats was much slower. Damaged blood vessels at the lesion site after thoracic SCI impacted the vascular response upon neuronal activation in the lumbar spinal cord. This observation is important in the study of spinal cord function after SCI by imaging techniques based on haemodynamics (blood oxygenation level-dependent using functional magnetic resonance imaging (BOLD fMRI) and optical imaging). In conclusion, our results indicate that new avenues quantifying the influence of vascular plumbing will have to be developed to explore the efficacy of rehabilitation and pharmacological therapies by haemodynamic imaging.

Development of a multi-channel system for intrinsic cardiac neural recording.

Recent clinical evidence suggests that abnormal neural input can contribute to the onset perpetuation of atrial arrhythmias, such that neural elements have become potential targets for ablation. A better understanding of the influence of the cardiac autonomous nervous system is required to improve therapy. We have developed a multi-channel system to record neural activity simultaneously at different intra and pericardiac locations. The paper presents the specific requirements to be met for recording neuronal extracellular potentials in these repertoires of neurons and the solutions that were adopted.