Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury

Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.

Axial MRI biomarkers of spinal cord damage to predict future walking and motor function: a retrospective study

Study design Retrospective. Objectives Primary: to assess if axial damage ratios are predictors of future walking after spinal cord injury (SCI), and if they add any predictive value if initial neurological impairment grades are available. Secondary: to determine if lateral spinal cord regions are predictors of future lower extremity motor scores (LEMS). Setting University/hospital. Methods Axial T2-weighted MRIs were used. Axial damage ratios and non-damaged lateral cord volumes were calculated. Each participant answered at 1 year after SCI, “Are you able to walk for 150 feet? (45.72 meters)” For the secondary aim, right and left LEMS were used. Results In total, 145 participants were selected. Individuals that could walk had smaller ratios than those that were unable. Walking and axial damage ratios were negatively correlated. A 0.374 ratio cut-off showed optimal sensitivity/specificity. When initial neurological grades were used, axial damage ratios did not add predictive value. Forty-two participants had LEMS available and were included for the secondary aim. Right cord regions and right LEMS were positively correlated and left regions and left LEMS, but these variables were also correlated with each other. Conclusions Axial damage ratios were significant predictors of walking ability 1 year after SCI. However, this measure did not add predictive value over initial neurological grades. Lateral cord regions correlated with same-side LEMS, but the opposite was also found, calling this biomarker’s specificity into question. Axial damage ratios may be useful in predicting walking after SCI if initial neurological grades are unavailable. Sponsorship This research was funded by a National Institutes of Health award, National Institute of Child Health and Development—NIH R03HD094577.

Distribution of Spinal Sensitization Evoked by Inflammatory Pain Using Local Spinal Cord Glucose Utilization Combined with 3H-Phorbol 12,13-Dibutyrate Binding in Rats

Aims. Hyperalgesia following tissue injury is induced by plasticity in neurotransmission. Few investigators have considered the ascending input which activates the superficial of spinal cord. The aim was to examine neurotransmission and nociceptive processing in the spinal cord after mustard-oil (MO) injection. Both in vitro and in vivo autoradiographs were employed for neuronal activity and transmission in discrete spinal cord regions using the 14C-2-deoxyglucose method and 3H-phorbol 12,13-dibutyrate (3H-PDBu) binding sites. Methods. To quantify the hyperalgesia evoked by MO, the flinching was counted for 60 min after MO (20%, 50 μL) injection in Wistar rats. Simultaneous determination of 14C-2-deoxyglucose and 3H-PDBu binding was used for a direct observation of neuronal/metabolic changes and intracellular signaling in the spinal cord. Results. MO injection evoked an increase in flinching for 60 min. LSCGU significantly increased in the Rexed I-II with 3H-PDBu binding in the ipsilateral side of spinal cord. Discussion. We clearly demonstrated that the hyperalgesia is primarily relevant to increased neuronal activation with PKC activation in the Rexed I-II of the spinal cord. In addition, functional changes such as “neuronal plasticity” may result in increased neuronal excitability and a central sensitization.

Regional differences of proliferation activity in the spinal cord ependyma of adult rats

Increased proliferation activity in the central canal ependyma of adult rodent spinal cord was described after injury and is thought to participate in recovery processes. Proliferation activity is scarce under physiological conditions, but still could be of importance, as in vitro studies showed that the spinal cord ependyma is an internal source of neural stem cells. Data from these studies indicate that there are regional differences in the distribution of proliferation activity along the rostro-caudal axis. We analyzed the proliferation activities in the ependyma within the entire extent of intact adult rat spinal cord. To identify proliferating cells we performed immunohistochemistry either for cell cycle S-phase marker BrdU or for the nuclear protein Ki-67. BrdU and Ki-67 positive cells were counted on sections selected from four spinal cord regions — cervical, thoracic, lumbar and sacral/coccygeal. Analysis showed that the number of BrdU positive cells within the ependyma was very low in all subdivisions of the spinal cord. Both BrdU and Ki-67 labeling revealed a significantly higher number of proliferating cells in the ependyma of sacrococcygeal part in comparison to all other spinal cord regions, suggesting that the caudal spinal cord might have potentially higher regeneration capacity compared to more rostral parts.