Elevated Mmp-9 in the Lumbar Cord Early After Thoracic Spinal Cord Injury Impedes Motor Relearning in Mice.
Elevated mmp-9 in the lumbar cord early after thoracic spinal cord injury impedes motor relearning in mice.
J Neurosci. 2013 Aug 7; 33(32): 13101-11
Hansen CN, Fisher LC, Deibert RJ, Jakeman LB, Zhang H, Noble-Haeusslein L, White S, Basso DM
Spinal cord injury results in distant pathology around putative locomotor networks that may jeopardize the recovery of locomotion. We previously showed that activated microglia and increased cytokine expression extend at least 10 segments below the injury to influence sensory function. Matrix metalloproteinase-9 (MMP-9) is a potent regulator of acute neuroinflammation. Whether MMP-9 is produced remote to the injury or influences locomotor plasticity remains unexamined. Therefore, we characterized the lumbar enlargement after a T9 spinal cord injury in C57BL/6 (wild-type [WT]) and MMP-9-null (knock-out [KO]) mice. Within 24 h, resident microglia displayed an activated phenotype alongside increased expression of progelatinase MMP-3 in WT mice. By 7 d, increases in active MMP-9 around lumbar vasculature and production of proinflammatory TNF-? were evident. Deletion of MMP-9 attenuated remote microglial activation and restored TNF-? expression to homeostatic levels. To determine whether MMP-9 impedes locomotor plasticity, we delivered lumbar-focused treadmill training in WT and KO mice during early (2-9 d) or late (35-42 d) phases of recovery. Robust behavioral improvements were observed by 7 d, when only trained KO mice stepped in the open field. Locomotor improvements were retained for 4 weeks as identified using state of the art mouse kinematics. Neither training nor MMP-9 depletion alone promoted recovery. The same intervention delivered late was ineffective, suggesting that lesion site sparing is insufficient to facilitate activity-based training and recovery. Our work suggests that by attenuating remote mechanisms of inflammation, acute treadmill training can harness endogenous spinal plasticity to promote robust recovery. HubMed – rehab
Autonomic Dysreflexia Causes Chronic Immune Suppression after Spinal Cord Injury.
J Neurosci. 2013 Aug 7; 33(32): 12970-12981
Zhang Y, Guan Z, Reader B, Shawler T, Mandrekar-Colucci S, Huang K, Weil Z, Bratasz A, Wells J, Powell ND, Sheridan JF, Whitacre CC, Rabchevsky AG, Nash MS, Popovich PG
Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known. Data presented herein indicate that AD causes immune suppression. Using in vivo telemetry, we show that AD develops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency of AD increases, there is a corresponding increase in splenic leucopenia and immune suppression. Experimental activation of spinal sympathetic reflexes in SCI mice (e.g., via colorectal distension) elicits AD and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. Reversal of postinjury immune suppression in SCI mice can be achieved by pharmacological inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function. HubMed – rehab
Grip strength and its determinants among older people in different healthcare settings.
Age Ageing. 2013 Aug 7;
Roberts HC, Syddall HE, Sparkes J, Ritchie J, Butchart J, Kerr A, Cooper C, Sayer AA
low muscle strength is central to geriatric syndromes including sarcopenia and frailty. It is well described in community-dwelling older people, but the epidemiology of grip strength of older people in rehabilitation or long-term care has been little explored.to describe grip strength of older people in rehabilitation and nursing home settings.cross-sectional epidemiological study.three healthcare settings in one town.hundred and one inpatients on a rehabilitation ward, 47 community rehabilitation referrals and 100 nursing home residents.grip strength, age, height, weight, body mass index, number of co-morbidities and medications, Barthel score, Mini-Mental State Examination (MMSE), nutritional status and number of falls in the last year were recorded.grip strength differed substantially between healthcare settings for both men and women (P < 0.0001). Nursing home residents had the lowest age-adjusted mean grip strength and community rehabilitation referrals the highest. Broadly higher grip strength was associated in univariate analyses with younger age, greater height and weight, fewer comorbidities, higher Barthel score, higher MMSE score, better nutritional status and fewer falls. However, after mutual adjustment for these factors, the difference in grip strength between settings remained significant. The Barthel score was the characteristic most strongly associated with grip strength.older people in rehabilitation and care home settings had lower grip strength than reported for those living at home. Furthermore grip strength varied widely between healthcare settings independent of known major influences. Further research is required to ascertain whether grip strength may help identify people at risk of adverse health outcomes within these settings. HubMed – rehab
Evaluation of patellofemoral joint in ADVANCE(®) Medial-pivot total knee arthroplasty.
Int Orthop. 2013 Aug 8;
Chinzei N, Ishida K, Matsumoto T, Kuroda Y, Kitagawa A, Kuroda R, Akisue T, Nishida K, Kurosaka M, Tsumura N
ADVANCE® Medial Pivot (MP) (Wright Medical) total knee arthroplasty (TKA) was established to replicate normal tibio-femoral knee joint kinematics, however, its influence on the patello-femoral (PF) joint is unclear. The purpose in this study was to assess the PF joint conditions in Advance MP TKA, via radiography and three-dimensional image-matching software.Ten subjects with osteoarthritis were treated with the ADVANCE MP TKA. Pre-operatively and one month after surgery, skyline views at 30, 60, and 90° of flexion were taken, and patella shift and tilt were measured. With 2D-3D registration techniques using software, implant orientations were matched with the pre-operative CT and changes in the anterior part of the femoral prosthesis, condylar twist angle (CTA) for femoral rotation, and tibial rotation were evaluated. The relationships between morphological and rotational changes were evaluated.There were significant differences in patella tilt at 60° and patella shift at all angles between pre- and post-operation (p?0.05). No correlation was found between morphological changes in the anterior femur with patella tilt and shift. A positive correlation between postoperative CTA and patella shift at 90° was found (p?0.05); however, no correlation was found between rotational alignment of the tibial component and patella tilt and shift.ADVANCE MP TKA changed patello-femoral joint kinematics, compared to that found before surgery. The kinematic features were mainly due to the design concepts for tibio-femoral joint motion, indicating the difficulty to reproduce normal patello-femoral joint kinematics after TKA. HubMed – rehab
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