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Item Assessment of white matter loss using bond-selective photoacoustic imaging in a rat model of contusive spinal cord injury(Mary Ann Liebert, 2014-12-15) Wu, Wei; Wang, Pu; Cheng, Ji-Xin; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineWhite 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.Item Cortical PKC inhibition promotes axonal regeneration of the corticospinal tract and forelimb functional recovery after cervical dorsal spinal hemisection in adult rats(Oxford University Press, 2014-11) Wang, Xiaofei; Hu, Jianguo; She, Yun; Smith, George M.; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineOur previous study shows that conventional protein kinases C (cPKCs) are key signaling mediators that are activated by extracellular inhibitory molecules. Inhibition of cPKC by intrathecal infusion of a cPKC inhibitor, GÖ6976, into the site of dorsal hemisection (DH) induces regeneration of lesioned dorsal column sensory, but not corticospinal tract (CST), axons. Here, we investigated whether a direct cortical delivery of GÖ6976 into the soma of corticospinal neurons promotes regeneration of CST and the recovery of forelimb function in rats with cervical spinal cord injuries. We report that cortical delivery of GÖ6976 reduced injury-induced activation of conventional PKCα and PKCβ1 in CST neurons, promoted regeneration of CST axons through and beyond a cervical DH at C4, formed new synapses on target neurons caudal to the injury, and enhanced forelimb functional recovery in adult rats. When combined with lenti-Chondroitinase ABC treatment, cortical administration of GÖ6976 promoted even greater CST axonal regeneration and recovery of forelimb function. Thus, this study has demonstrated a novel strategy that can promote anatomical regeneration of damaged CST axons and partial recovery of forelimb function. Importantly, such an effect is critically dependent on the efficient blockage of injury-induced PKC activation in the soma of layer V CST neurons.Item Dietary intake and adherence to the 2010 Dietary Guidelines for Americans among individuals with chronic spinal cord injury: a pilot study(Maney Publishing, 2014-11) Lieberman, Jesse; Goff, David; Hammond, Flora; Schreiner, Pamela; Norton, H. James; Dulin, Michael; Zhou, Xia; Steffen, Lyn; Department of Physical Medicine and Rehabilitation, IU School of MedicineOBJECTIVE: To investigate dietary intake and adherence to the 2010 Dietary Guidelines for Americans in individuals with chronic spinal cord injury (SCI) and able-bodied individuals. DESIGN: A pilot study of dietary intake among a sample of individuals with SCI >1 year ago from a single site compared with able-bodied individuals. PARTICIPANTS/METHODS: One hundred black or white adults aged 38-55 years old with SCI >1 year and 100 age-, sex-, and race-matched adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary intake was assessed by the CARDIA dietary history. Linear regression analysis was used to compare dietary intake between the subjects with SCI and those enrolled in the CARDIA study. Further, adherence to the 2010 Dietary Guidelines for dairy, fruits, and vegetables, and whole-grain foods was assessed. RESULTS: Compared with CARDIA participants, participants with SCI consumed fewer daily servings of dairy (2.10 vs. 5.0, P < 0.001), fruit (2.01 vs. 3.64, P = 0.002), and whole grain foods (1.20 vs. 2.44 P = 0.007). For each food group, fewer participants with SCI met the recommended servings compared with the CARDIA participants. Specifically, the participants with SCI and in CARDIA who met the guidelines were, respectively: dairy, 22% vs. 54% (P < 0.001), fruits and vegetables 39% vs. 70% (P = 0.001), and whole-grain foods 8% vs. 69.6% (P = 0.001). CONCLUSIONS: Compared with able-bodied individuals, SCI participants consumed fewer daily servings of fruit, dairy, and whole grain foods than proposed by the 2010 Dietary Guideline recommendations. Nutrition education for this population may be warranted.Item Long-term survival, axonal growth-promotion, and myelination of Schwann cells grafted into contused spinal cord in adult rats(Elsevier, 2014-11) Wang, Xiaofei; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineSchwann cells (SCs) have been considered to be one of the most promising cell types for transplantation to treat spinal cord injury (SCI) due to their unique growth-promoting properties. Despite the extensive use as donor cells for transplantation in SCI models, the fate of SCs is controversial due in part to the lack of a reliable marker for tracing the grafted SCs. To precisely assess the fate and temporal profile of transplanted SCs, we isolated purified SCs from sciatic nerves of adult transgenic rats overexpressing GFP (SCs-GFP). SCs-GFP were directly injected into the epicenter of a moderate contusive SCI at the mid-thoracic level at 1week post-injury. The number of SCs-GFP or SCs-GFP labeled with Bromodeoxyuridine (BrdU) was quantified at 5min, 1day, and 1, 2, 4, 12 and 24weeks after cell injection. Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, footfall error, thermal withdrawal latency, and footprint analysis were performed before and after the SCs-GFP transplantation. After transplantation, SCs-GFP quickly filled the lesion cavity. A remarkable survival of grafted SCs-GFP up to 24weeks post-grafting was observed with clearly identified SC individuals. SCs-GFP proliferated after injection, peaked at 2weeks (26% of total SCs-GFP), decreased thereafter, and ceased at 12weeks post-grafting. Although grafted SCs-GFP were mainly confined within the border of surrounding host tissue, they migrated along the central canal for up to 5.0mm at 4weeks post-grafting. Within the lesion site, grafted SCs-GFP myelinated regenerated axons and expressed protein zero (P0) and myelin basic protein (MBP). Within the SCs-GFP grafts, new blood vessels were formed. Except for a significant decrease of angle of rotation in the footprint analysis, we did not observe significant behavioral improvements in BBB locomotor rating scale, thermal withdrawal latency, or footfall errors, compared to the control animals that received no SCs-GFP. We conclude that SCs-GFP can survive remarkably well, proliferate, migrate along the central canal, and myelinate regenerated axons when being grafted into a clinically-relevant contusive SCI in adult rats. Combinatorial strategies, however, are essential to achieve a more meaningful functional regeneration of which SCs may play a significant role.Item PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury(Elsevier, 2014-06-24) Walker, Chandler L.; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineCervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p < 0.01) and Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56 ± 0.01 vs. bpV: 0.64 ± 0.02; p < 0.05) and at the epicenter (Veh: 0.4175 ± 0.03 vs. bpV: 0.5400 ± 0.03; p < 0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109 ± 5.3 vs. Veh: 77 ± 2.7/mm2; p < 0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0 ± 0.02 vs. Veh: 0.77 ± 0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.