The role of neuronal plasticity in cervical spondylotic myelopathy surgery: functional assessment and prognostic implication.

Cervical spondylotic myelopathy (CSM) is a degenerative disease representing the most common spinal cord disorder in the adult population. It is characterized by chronic compression leading to neurological dysfunction due to static and dynamic injury of the spinal cord in cervical spine. These insidious damage mechanisms can result in the reorganization of cortical and subcortical areas. The cerebral cortex can reorganize due to spinal cord injury and may play a role in preserving neurological function. To date, the gold standard treatment of cervical myelopathy is surgery, comprising anterior, posterior, and combined approaches. However, the complex physiologic recovery processes involving cortical and subcortical neural reorganization following surgery are still inadequately understood. It has been demonstrated that diffusion MRI and functional imaging and techniques, such as transcranial magnetic stimulation (TMS) or functional magnetic resonance imaging (fMRI), can provide new insights into the diagnosis and prognosis of CSM. This review aims to shed light on the state-of-the-art regarding the pattern of cortical and subcortical areas reorganization and recovery before and after surgery in CSM patients, underlighting the critical role of neuroplasticity.

Spinal cord injury as an indicator of abuse in forensic assessment of abusive head trauma (AHT).

Abusive head trauma (AHT) in children is notoriously one of the most challenging diagnoses for the forensic pathologist. The pathological "triad", a combination of intracranial subdural haematoma, cerebral oedema with hypoxic-ischaemic changes and retinal haemorrhages, is frequently argued to be insufficient to support a corroborated verdict of abuse. Data from all available English-language scientific literature involving radiological and neuropathological spinal cord examination is reviewed here in order to assess the contribution of spinal cord changes in differentiating abusive from accidental head trauma. In agreement with the statistically proven association between spinal subdural haemorrhage (SDH) and abuse (Choudhary et al. in Radiology 262:216-223, 2012), spinal blood collection proved to be the most indicative finding related to abusive aetiology. The incidence of spinal blood collection is as much as 44-48% when all the spinal cord levels are analysed as opposed to just 0-18% when the assessment is performed at cervical level only, in agreement with the evidence of the most frequent spinal SDH location at thoracolumbar rather than cervical level. In this review, the source of spinal cord blood collection and how the age of the child relates to the position of spinal cord lesions is also discussed. We concluded that the ante mortem MRI examination and post mortem examination of whole-length spinal cord is of fundamental interest for the assessment of abuse in the forensic setting.

Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury.

The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management.

Real-Time Assessment of Spinal Cord Microperfusion in a Porcine Model of Ischemia/Reperfusion.

Spinal cord injury is a devastating complication of aortic repair. Despite developments for the prevention and treatment of spinal cord injury, its incidence is still considerably high and therefore, influences patient outcome. Microcirculation plays a key role in tissue perfusion and oxygen supply and is often dissociated from macrohemodynamics. Thus, direct evaluation of spinal cord microcirculation is essential for the development of microcirculation-targeted therapies and the evaluation of existing approaches in regard to spinal cord microcirculation. However, most of the methods do not provide real-time assessment of spinal cord microcirculation. The aim of this study is to describe a standardized protocol for real-time spinal cord microcirculatory evaluation using laser-Doppler needle probes directly inserted in the spinal cord. We used a porcine model of ischemia/reperfusion to induce deterioration of the spinal cord microcirculation. In addition, a fluorescent microsphere injection technique was used. Initially, animals were anesthetized and mechanically ventilated. Thereafter, laser-Doppler needle probe insertion was performed, followed by the placement of cerebrospinal fluid drainage. A median sternotomy was performed for exposure of the descending aorta to perform aortic cross-clamping. Ischemia/reperfusion was induced by supra-celiac aortic cross-clamping for a total of 48 min, followed by reperfusion and hemodynamic stabilization. Laser-Doppler Flux was performed in parallel with macrohemodynamic evaluation. In addition, automated cerebrospinal fluid drainage was used to maintain a stable cerebrospinal pressure. After completion of the protocol, animals were sacrificed, and the spinal cord was harvested for histopathological and microsphere analysis. The protocol reveals the feasibility of spinal cord microperfusion measurements using laser-Doppler probes and shows a marked decrease during ischemia as well as recovery after reperfusion. Results showed comparable behavior to fluorescent microsphere evaluation. In conclusion, this new protocol might provide a useful large animal model for future studies using real-time spinal cord microperfusion assessment in ischemia/reperfusion conditions.

Harnessing the Secretome of Mesenchymal Stromal Cells for Traumatic Spinal Cord Injury: Multicell Comparison and Assessment of In Vivo Efficacy.

Cell therapy offers significant promise for traumatic spinal cord injury (SCI), which despite many medical advances, has limited treatment strategies. Able to address the multifactorial and dynamic pathophysiology of SCI, cells present various advantages over standard pharmacological approaches. However, the use of live cells is also severely hampered by logistical and practical considerations. These include specialized equipment and expertise, standardization of cell stocks, sustained cell viability post-thawing, and cryopreservation-induced delayed-onset cell death. For this reason, we suggest a novel and clinically translatable alternative to live-cell systemic infusion, which retains the efficacy of the latter while overcoming many of its limitations. This strategy involves the administration of concentrated cell secretome and exploits the trophic mechanism by which stromal cells function. In this study, we compare the efficacy of intravenously delivered concentrated conditioned media (CM) from human umbilical cord matrix cells (HUCMCs), bone marrow mesenchymal stromal cells, as well as newborn and adult fibroblasts in a rat model of moderately severe cervical clip compression/contusion injury (C7--T1, 35 g). This is further paired with a thorough profile of the CM cytokines, chemokines, and angiogenic factors. The HUCMC-derived CM was most effective at limiting acute (48 h post-SCI) vascular pathology, specifically lesion volume, and functional vascularity. Principle component analysis (PCA), hierarchical clustering, and interaction analysis of proteins highly expressed in the HUCMC secretome suggest involvement of the MAPK/ERK, JAK/STAT, and immune cell migratory pathways. This "secretotherapeutic" strategy represents a novel and minimally invasive method to target multiple organ systems and several pathologies shortly after traumatic SCI.

Prognostic factors for medical and productivity costs, and return to work after trauma.

AIM: The aim of this study was to determine prognostic factors for medical and productivity costs, and return to work (RTW) during the first two years after trauma in a clinical trauma population. METHODS: This prospective multicentre observational study followed all adult trauma patients (≥18 years) admitted to a hospital in Noord-Brabant, the Netherlands from August 2015 through November 2016. Health care consumption, productivity loss and return to work were measured in questionnaires at 1 week, 1, 3, 6, 12 and 24 months after injury. Data was linked with hospital registries. Prognostic factors for medical costs and productivity costs were analysed with log-linked gamma generalized linear models. Prognostic factors for RTW were assessed with Cox proportional hazards model. The predictive ability of the models was assessed with McFadden R2 (explained variance) and c-statistics (discrimination). RESULTS: A total of 3785 trauma patients (39% of total study population) responded to at least one follow-up questionnaire. Mean medical costs per patient (€9,710) and mean productivity costs per patient (€9,000) varied widely. Prognostic factors for high medical costs were higher age, female gender, spine injury, lower extremity injury, severe head injury, high injury severity, comorbidities, and pre-injury health status. Productivity costs were highest in males, and in patients with spinal cord injury, high injury severity, longer length of stay at the hospital and patients admitted to the ICU. Prognostic factors for RTW were high educational level, male gender, low injury severity, shorter length of stay at the hospital and absence of comorbidity. CONCLUSIONS: Productivity costs and RTW should be considered when assessing the economic impact of injury in addition to medical costs. Prognostic factors may assist in identifying high cost groups with potentially modifiable factors for targeted preventive interventions, hence reducing costs and increasing RTW rates.

The standing and walking assessment tool for individuals with spinal cord injury: A qualitative study of validity and clinical use.

Context/Objective: The Spinal Cord Injury (SCI) Standing and Walking Assessment Tool (SWAT) combines stages of walking recovery with measures of balance and walking. It standardizes the timing and content of walking assessment in inpatient rehabilitation. The study aims were: (1) Evaluate the content validity of the SWAT stages of walking recovery, and (2) Understand physical therapists' (PTs) experiences using the SWAT to gauge acceptance, implementation and impact. Design: Qualitative, exploratory study. Setting: Nine Canadian rehabilitation hospitals. Participants: Thirty-four PTs who had used the SWAT ≥10 times. Interventions: Seven focus group meetings were completed. Semi-structured questions queried the content, order and spacing of SWAT stages, and current SWAT use (i.e. processes, challenges, facilitators, impact on practice). Meetings were audio-recorded and transcribed. Themes and categories were derived through a conventional content analysis. Outcome Measure: Not applicable. Results: PTs agreed with the ordering and content of the SWAT stages, but reported unequal spacing between stages. Three themes related to PTs' use of the SWAT were identified: (1) Variable process: SWAT implementation varied across sites, PTs and patients. (2) Implementation challenges: unfamiliarity of the SWAT, lack of time, not required by place of work, and patients who are outliers or have poor gait quality. (3) Potential to influence clinical decision-making: the SWAT did not influence clinical decisions, but PTs recognized the potential of the tool to do so. Conclusions: Content validity of the SWAT stages was supported and implementation challenges identified. Variability in SWAT implementation may reflect the heterogeneity and person-centeredness of SCI rehabilitation.

The graded redefined assessment of strength sensibility and prehension version 2 (GV2): Psychometric properties.

Context: GRASSP Version 1 (GV1) was developed in 2010, is an upper extremity measure specifically designed to assess recovery after traumatic tetraplegia. A second version was developed to reduce length of the test and refine instructions/standardization. The purpose of this post hoc analysis was to calculate psychometric properties of GRASSP Version 2 (GV2). Design/Setting: A post-hoc analysis of datasets for the GRASSP cross-sectional (n = 72 chronic,) and longitudinal (n = 127 acute) studies was conducted. Reliability, validity and MDD were calculated from the chronic sample and responsiveness was re-calculated from the longitudinal sample. Both studies were observational. Participants: A chronic sample (n = 72) and acute longitudinal sample (n = 127) of individuals with traumatic tetraplegia (AIS A to D, NLI C2 to C8) were studied. Outcome Measures: GV1, the Spinal Cord Independence Measure III (SCIM), International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI) were administered in both studies at all centers and the Capabilities of the Upper Extremity Questionnaire (CUE-Q) was administered in North American sites only. GRASSP-Palmar Sensation, GRASSP-Prehension Performance subtest items included in GV2 were re-analyzed for reliability; validity, MDD and responsiveness. Results: Inter-rater and test-retest reliability for all subtests ranged between 0.849-0.971 and 0.950-0.971 respectively. Concurrent validity between domains of GV2 were positively and moderately (0.530-0.830, P < 0.0001) correlated to SCIM, SCIM self-care subscore (SS) and CUE-Q. MDD values were 4 and 3 points for sensation and prehension performance (single side). Responsiveness values were .84-.88 for GR-Sens and .93-1.22 for GR-PP respectively. Conclusions: GV2 retains excellent psychometric properties as does GV1.

The role of diffusion tensor imaging in the diagnosis, prognosis, and assessment of recovery and treatment of spinal cord injury: a systematic review.

OBJECTIVEDiffusion tensor imaging (DTI) is an MRI tool that provides an objective, noninvasive, in vivo assessment of spinal cord injury (SCI). DTI is significantly better at visualizing microstructures than standard MRI sequences. In this imaging modality, the direction and amplitude of the diffusion of water molecules inside tissues is measured, and this diffusion can be measured using a variety of parameters. As a result, the potential clinical application of DTI has been studied in several spinal cord pathologies, including SCI. The aim of this study was to describe the current state of the potential clinical utility of DTI in patients with SCI and the challenges to its use as a tool in clinical practice.METHODSA search in the PubMed database was conducted for articles relating to the use of DTI in SCI. The citations of relevant articles were also searched for additional articles.RESULTSAmong the most common DTI metrics are fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Changes in these metrics reflect changes in tissue integrity. Several DTI metrics and combinations thereof have demonstrated significant correlations with clinical function both in model species and in humans. Its applications encompass the full spectrum of the clinical assessment of SCI including diagnosis, prognosis, recovery, and efficacy of treatments in both the spinal cord and potentially the brain.CONCLUSIONSDTI and its metrics have great potential to become a powerful clinical tool in SCI. However, the current limitations of DTI preclude its use beyond research and into clinical practice. Further studies are needed to significantly improve and resolve these limitations as well as to determine reliable time-specific changes in multiple DTI metrics for this tool to be used accurately and reliably in the clinical setting.

Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.

There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. Axial diffusion tensor images using an inner field of view DTI sequence were acquired to cover the entire cervical and thoracic SC. Regions of interest were drawn on the SC WM: right and left lateral (motor), ventral (motor), and dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI of the cord, a one way analysis of variance with pooled t test was performed. A stepwise regression analysis was performed to assess the correlation between DTI metrics and clinical scores. In motor and sensory tracts, fractional anisotropy (FA) and axial diffusivity (AD) were significantly decreased in the proximal segments of the caudal cord. In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.

Measuring pain phenomena after spinal cord injury: Development and psychometric properties of the SCI-QOL Pain Interference and Pain Behavior assessment tools.

OBJECTIVE: To develop modern patient-reported outcome measures that assess pain interference and pain behavior after spinal cord injury (SCI). DESIGN: Grounded-theory based qualitative item development; large-scale item calibration field-testing; confirmatory factor analyses; graded response model item response theory analyses; statistical linking techniques to transform scores to the Patient Reported Outcome Measurement Information System (PROMIS) metric. SETTING: Five SCI Model Systems centers and one Department of Veterans Affairs medical center in the United States. PARTICIPANTS: Adults with traumatic SCI. INTERVENTIONS: N/A. OUTCOME MEASURES: Spinal Cord Injury - Quality of Life (SCI-QOL) Pain Interference item bank, SCI-QOL Pain Interference short form, and SCI-QOL Pain Behavior scale. RESULTS: Seven hundred fifty-seven individuals with traumatic SCI completed 58 items addressing various aspects of pain. Items were then separated by whether they assessed pain interference or pain behavior, and poorly functioning items were removed. Confirmatory factor analyses confirmed that each set of items was unidimensional, and item response theory analyses were used to estimate slopes and thresholds for the items. Ultimately, 7 items (4 from PROMIS) comprised the Pain Behavior scale and 25 items (18 from PROMIS) comprised the Pain Interference item bank. Ten of these 25 items were selected to form the Pain Interference short form. CONCLUSIONS: The SCI-QOL Pain Interference item bank and the SCI-QOL Pain Behavior scale demonstrated robust psychometric properties. The Pain Interference item bank is available as a computer adaptive test or short form for research and clinical applications, and scores are transformed to the PROMIS metric.

Comparative assessment of phototherapy protocols for reduction of oxidative stress in partially transected spinal cord slices undergoing secondary degeneration.

BACKGROUND: Red/near-infrared light therapy (R/NIR-LT) has been developed as a treatment for a range of conditions, including injury to the central nervous system (CNS). However, clinical trials have reported variable or sub-optimal outcomes, possibly because there are few optimized treatment protocols for the different target tissues. Moreover, the low absolute, and wavelength dependent, transmission of light by tissues overlying the target site make accurate dosing problematic. RESULTS: In order to optimize light therapy treatment parameters, we adapted a mouse spinal cord organotypic culture model to the rat, and characterized myelination and oxidative stress following a partial transection injury. The ex vivo model allows a more accurate assessment of the relative effect of different illumination wavelengths (adjusted for equal quantal intensity) on the target tissue. Using this model, we assessed oxidative stress following treatment with four different wavelengths of light: 450 nm (blue); 510 nm (green); 660 nm (red) or 860 nm (infrared) at three different intensities: 1.93 × 10(16) (low); 3.85 × 10(16) (intermediate) and 7.70 × 10(16) (high) photons/cm(2)/s. We demonstrate that the most effective of the tested wavelengths to reduce immunoreactivity of the oxidative stress indicator 3-nitrotyrosine (3NT) was 660 nm. 860 nm also provided beneficial effects at all tested intensities, significantly reducing oxidative stress levels relative to control (p ≤ 0.05). CONCLUSIONS: Our results indicate that R/NIR-LT is an effective antioxidant therapy, and indicate that effective wavelengths and ranges of intensities of treatment can be adapted for a variety of CNS injuries and conditions, depending upon the transmission properties of the tissue to be treated.

Safety assessment of epidural wire electrodes for cough production in a chronic pig model of spinal cord injury.

BACKGROUND: It is our hypothesis that high intensity spinal cord stimulation (SCS) to restore an effective cough mechanism using wire leads, will result in significant activation of target neurons without tissue injury or electrode corrosion. METHODS: Adult mini-pigs underwent chronic spinal cord compression, followed by implantation of parallel wire leads on the dorsal epidural surface of the spinal cord, with stimulation contacts at the T9 and T12, and control electrode contacts at the T2 and T5 levels. After 3 months of daily SCS, airway pressure generation (P), tissue in the area of the stimulating and control electrodes and electrode leads were examined. P was also assessed in acute animals, which served as controls. RESULTS: Mean P at FRC was 54±5cmH2O and 109±11cmH2O in the control and chronically stimulated animals, respectively (p<0.05). There was minimal tissue reaction in the area of the stimulating and control electrodes. All sets of leads revealed no evidence of electrode corrosion. COMPARISON WITH EXISTING METHODS: Previous porcine models of chronic spinal cord injury (SCI) were developed to study neurological and regenerative outcomes. Our method of chronic SCI porcine model was developed to evaluate the safety of electrical SCS to restore expiratory muscle function. CONCLUSION: Chronic SCS with wire lead electrodes results in significant increases in P without evidence of significant adverse tissue reaction, nor evidence of electrode corrosion. This method may be a safe and useful technique to restore a functional cough in spinal cord injured subjects.

Longitudinal assessment of spinal cord injuries in nonhuman primates with quantitative magnetization transfer.

PURPOSE: This study aimed to evaluate the reproducibility and specificity of quantitative magnetization transfer (qMT) imaging for monitoring spinal cord injuries (SCIs). METHODS: MRI scans were performed in anesthetized monkeys at 9.4T, before and serially after a unilateral lesion of the cervical spinal cord. A two-pool fitting model was used to derive qMT parameters. RESULTS: qMT measures were reproducible across normal subjects, with an average pool size ratio (PSR) of 0.086 ± 0.003 (mean ± SD) for gray matter, and 0.120 ± 0.005 for white matter, respectively. Compared with normal gray matter, the PSR of abnormal tissues rostral and caudal to the injury site decreased by 19.5% (P < 0.05), while the PSR of the cyst-like volume decreased drastically weeks after SCI. Strong correlations in cyst-like regions were observed between PSR and other MRI measures including longitudinal relaxation rate (R1 ), apparent diffusion coefficient and fractional anisotropy (FA). Decreased PSR and FA values correlated well with demyelination in abnormal tissues. CONCLUSION: The qMT parameters provide robust and specific information about the molecular and cellular changes produced by SCI. PSR detected demyelination and loss of macromolecules in abnormal tissue regions rostral and caudal to the cyst/lesion sites.

Functional and morphological assessment of diaphragm innervation by phrenic motor neurons.

This protocol specifically focuses on tools for assessing phrenic motor neuron (PhMN) innervation of the diaphragm at both the electrophysiological and morphological levels. Compound muscle action potential (CMAP) recording following phrenic nerve stimulation can be used to quantitatively assess functional diaphragm innervation by PhMNs of the cervical spinal cord in vivo in anesthetized rats and mice. Because CMAPs represent simultaneous recording of all myofibers of the whole hemi-diaphragm, it is useful to also examine the phenotypes of individual motor axons and myofibers at the diaphragm NMJ in order to track disease- and therapy-relevant morphological changes such as partial and complete denervation, regenerative sprouting and reinnervation. This can be accomplished via whole-mount immunohistochemistry (IHC) of the diaphragm, followed by detailed morphological assessment of individual NMJs throughout the muscle. Combining CMAPs and NMJ analysis provides a powerful approach for quantitatively studying diaphragmatic innervation in rodent models of CNS and PNS disease.

Reliability of surface EMG as an assessment tool for trunk activity and potential to determine neurorecovery in SCI.

STUDY DESIGN: Reliability and validity study. OBJECTIVE: This study investigates the responsiveness and reliability of the brain motor control assessment (BMCA) as a standardized neurophysiological assessment tool to: (i) characterize trunk neural activity in neurologically-intact controls; (ii) measure and quantify neurorecovery of trunk after spinal cord injury (SCI). SETTING: Kessler Foundation Research Center, West Orange, NJ. METHODS: A standardized BMCA protocol was performed to measure surface electromyography (sEMG) recordings for seven bilateral trunk muscles on 15 able-bodied controls during six maneuvers (inhalation, exhalation, neck flexion, jendrassik, unilateral grip). Additionally, sEMG recordings were analyzed for one chronic SCI individual before electrical stimulation (ES), after ES of the lower extremities while supine, and after active stand training using body-weight support with bilateral ES. sEMG recordings were collected on bilateral erector spinae, internal and external obliques, upper and middle trapezius, biceps and triceps. For each maneuver a voluntary response index was calculated: incorporating the magnitude of sEMG signal and a similarity index (SI), which quantifies the distribution of activity across all muscles. RESULTS: Among all maneuvers, the SI presented reproducible assessment of trunk-motor function within (ICC: 0.860-0.997) and among (P⩾0.22) able-bodied individuals. In addition, potential changes were measured in a chronic SCI individual after undergoing two intensive ES protocols. CONCLUSION: The BMCA provides reproducible characterization of trunk activity in able-bodied individuals, lending credence for its use in neurophysiological assessment of motor control. Additionally, the BMCA as an assessment tool to measure neurorecovery in an individual with chronic SCI after intense ES interventions was demonstrated.

Assessment of white matter loss using bond-selective photoacoustic imaging in a rat model of contusive spinal cord injury.

White matter (WM) loss is a critical event after spinal cord injury (SCI). Conventionally, such loss has been measured with histological and histochemical approaches, although the procedures are complex and may cause artifact. Recently, coherent Raman microscopy has been proven to be an emerging technology to study de- and remyelination of the injured spinal cord; however, limited penetration depth and small imaging field prevent it from comprehensive assessments of large areas of damaged tissues. Here, we report the use of bond-selective photoacoustic (PA) imaging with 1730-nm excitation, where the first overtone vibration of CH2 bond is located, to assess WM loss after a contusive SCI in adult rats. By employing the first overtone vibration of CH2 bond as the contrast, the mapping of the WM in an intact spinal cord was achieved in a label-free three-dimensional manner, and the physiological change of the spinal cord before and after injury was observed. Moreover, the recovery of the spinal cord from contusive injury with the treatment of a neuroprotective nanomedicine ferulic-acid-conjugated glycol chitosan (FA-GC) was also observed. Our study suggests that bond-selective PA imaging is a valuable tool to assess the progression of WM pathology after SCI as well as neuroprotective therapeutics in a label-free manner.