Background: Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.

Chondroitin sulfate (CS) proteoglycans are strong inhibitors of structural rearrangement after injuries of the adult CNS. In addition to CS chains, keratan sulfate (KS) chains are also covalently attached to some proteoglycans. CS and KS sometimes share the same core protein, but exist as independent sugar chains. However, the biological significance of KS remains elusive. Here, we addressed the question of whether KS is involved in plasticity after spinal cord injury. Keratanase II (K-II) specifically degraded KS, i.e., not CS, in vivo. This enzyme digestion promoted the recovery of motor and sensory function after spinal cord injury in rats. Consistent with this, axonal regeneration/ sprouting was enhanced in K-II-treated rats. K-II and the CS-degrading enzyme chondroitinase ABC exerted comparable effects in vivo and in vitro. However, these two enzymes worked neither additively nor synergistically. These data and further in vitro studies involving artificial proteoglycans (KS/CS-albumin) and heat-denatured or reduced/alkylated proteoglycans suggested that all three components of the proteoglycan moiety, i.e., the core protein, CS chains, and KS chains, were required for the inhibitory activity of proteoglycans. We conclude that KS is essential for, and has an impact comparable to that of CS on, postinjury plasticity. Our study also established that KS and CS are independent requirements for the proteoglycan-mediated inhibition of axonal regeneration/sprouting.

Study Design: Retrospective analysis of a prospectively database. Objectives: To identify factors associated with prolonged length of stay (LOS) in posterior /transforaminal lumbar interbody fusion (PLIF/TLIF). Methods: The subjects were patients who underwent PLIF/TLIF at 10 facilities from 2012 to 2014. A total of 1168 such patients with a mean age of 65.9 ± 12.5 years (range 18-87 years) were identified in the database. Operations were PLIF (n = 675), TLIF (n = 443), minimally invasive surgery (MIS)-PLIF (n = 22), and MIS-TLIF (n = 32). Age, gender, body mass index, ambulatory status, comorbidities, perioperative American Society of Anesthesiologists (ASA) grade, operative factors, and complications were examined. LOS was defined as the number of calendar days from the operation to hospital discharge. LOS was categorized as normal (<75th percentile) or prolonged (≥75th percentile). Results: The average LOS was 20.8 ± 9.8 days (range 7-77 days). There was a significant correlation between LOS and age ( P < .05). Reoperation during hospitalization was performed in 20 cases for surgical site infection (n = 12), epidural hematoma (n = 5), and screw misplacement (n = 3). In multivariate analysis, prolonged LOS was associated with preoperative variables of age ≥70 years (odds ratio [OR] 1.87, 95% CI 1.38-2.54), and ASA class ≥III (OR 1.52, 95% CI 1.04-2.25); surgical variables of open procedures (OR 5.84, 95% CI 1.74-19.63), fused levels ≥3 (OR 5.17, 95% CI 3.17-8.43), operative time ≥300 minutes (OR 1.88, 95% CI 1.15-3.07), and estimated blood loss ≥500 mL (OR 1.71, 95% 1.07-2.75). Conclusions: The factors identified in this study should help with obtaining informed consent, surgical planning and complication prevention to reduce health care costs associated with prolonged LOS.

We determined quantitative and qualitative alterations in lipids during the occurrence and progression of spinal cord injury (SCI) in rats to identify potential clinical indicators of SCI pathology. Imaging mass spectrometry (IMS) was used to visualize twelve molecular species of phosphatidylcholine (PC) on thin slices of spinal cord with SCI. In addition, twelve species of phospholipids and five species of prostaglandins (PGs) were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) of lipid extracts from control/injured spinal cords. Unique distribution patterns were observed for phospholipids with different fatty acid compositions, and distinct dynamic changes were seen in both their amounts and their distributions in tissue as tissue damage resulting from SCI progressed. In particular, PCs containing docosahexaenoic acid localized to the large nucleus in the anterior horn region at one day post-SCI and rapidly decreased thereafter. In contrast, PCs containing arachidonic acid (AA-PCs) were normally found in the posterior horn region and were intensely and temporarily elevated one week after SCI. Lysophosphatidylcholines (LPCs) also increased at the same SCI stage and in regions with elevated AA-PCs, indicating the release of AA and the production of PGs. Moreover, LC-ESI-MS/MS analysis of lipid extracts from the spinal cord tissue at the impact site demonstrated a peak in PGE2 that reflected the elevation/reduction pattern of AA-PCs and LPC. Although further investigation is required, we suggest that invasive immune cells that penetrated from the impaired blood-brain barrier at 1-2 weeks post-SCI may have produced LPCs, released AA from AA-PCs, and produced PGs in SCI tissue at sites enriched in AA-PCs/LPC.

Study Design:A review of a prospective database.Objectives:Surgery for elderly patients is increasing yearly due to aging of society and the desire for higher quality of life. The goal of the study was to examine perioperative complications in spine surgery in such patients.Methods:A multicenter study of surgical details and perioperative complications was performed in 35 patients aged older than 90 years who underwent spinal surgery, based on a review of a prospective database. The frequency and severity of complications were assessed, and the effects of patient-specific and surgical factors were examined. Major complications were defined as those that were life threatening, required reoperation in the perioperative period or left a permanent injury. Ambulatory function before and after surgery was also analyzed.Results:Perioperative complications occurred in 19 of the 35 cases (54%), and included 11 cases of postoperative delirium, most of which occurred after cervical spine surgery. There were 8 major complications (23%), including cerebral infarction (n = 3), coronary heart disease (n = 3), pulmonary embolism (n = 1), and angina (n = 1). Preoperative motor deficit, operative time, estimated blood loss, and instrumented fusion were significantly associated with major complications. An improved postoperative ambulatory status occurred in 61% of cases, with no change in 33%, and worsening in 2 cases (6%).Conclusions:Timing of surgery before paralysis progression and reduced surgical invasiveness are important considerations in treatment of the very elderly. Improved outcomes can be obtained with better management of spine surgery for patients aged 90 years or older.

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Surgical invasiveness, as reflected by number of fused levels, operation time, EBL and dural tear, was associated with reoperation. Fusion of two or more levels is a strong risk factor for reoperation within 2 years after initial PLIF/TLIF. These slides can be retrieved under Electronic Supplementary Material.

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