Journal ArticleDOI
Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.
D. Michele Basso,Lesley C. Fisher,Aileen J. Anderson,Lyn B. Jakeman,Dana M. McTigue,Phillip G. Popovich +5 more
TLDR
The differing behavioral response to SCI suggests inherent genetic factors significantly impact locomotor recovery and must be considered in studies with inbred or genetically engineered mouse strains.Abstract:
Genetically engineered mice are used extensively to examine molecular responses to spinal cord injury (SCI). Inherent strain differences may confound behavioral outcomes; therefore, behavioral characterization of several strains after SCI is warranted. The Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB) for rats has been widely used for SCI mice, but may not accurately reflect their unique recovery pattern. This study's purpose was to develop a valid locomotor rating scale for mice and to identify strain differences in locomotor recovery after SCI. We examined C57BL/6, C57BL/10, B10.PL, BALB/c, and C57BL/6x129S6 F1 strains for 42 days after mild, moderate, and severe contusive SCI or transection of the mid thoracic spinal cord. Contusions were created using the Ohio State University electromagnetic SCI device which is a displacement-driven model, and the Infinite Horizon device, which is a force-driven model. Attributes and rankings for the Basso Mouse Scale for Locomotion (BMS) were determined from frequency analyses of seven locomotor categories. Mouse recovery differed from rats for coordination, paw position and trunk instability. Disagreement occurred across six expert raters using BBB (p < 0.05) but not BMS to assess the same mice. BMS detected significant differences in locomotor outcomes between severe contusion and transection (p < 0.05) and SCI severity gradations resulting from displacement variations of only 0.1 mm (p < 0.05). BMS demonstrated significant face, predictive and concurrent validity. Novice BMS raters with training scored within 0.5 points of experts and demonstrated high reliability (0.92-0.99). The BMS is a sensitive, valid and reliable locomotor measure in SCI mice. BMS revealed significantly higher recovery in C57BL/10, B10.PL and F1 than the C57BL/6 and BALB/c strains after moderate SCI (p < 0.05). The differing behavioral response to SCI suggests inherent genetic factors significantly impact locomotor recovery and must be considered in studies with inbred or genetically engineered mouse strains.read more
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Journal ArticleDOI
Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.
Ravid Shechter,Anat London,Chen Varol,Catarina Raposo,Melania Cusimano,Gili Yovel,Asya Rolls,Matthias Mack,Stefano Pluchino,Gianvito Martino,Steffen Jung,Michal Schwartz +11 more
TL;DR: Using a mouse model of spinal injury, Michal Schwartz and colleagues tested the effect of macrophages on the recovery process and demonstrate an important anti-inflammatory role for a subset of infiltrating monocyte-derived macrophage that is dependent upon their expression of interleukin 10.
Journal ArticleDOI
From basics to clinical: a comprehensive review on spinal cord injury.
TL;DR: An extensive overview of SCI research, as well as its clinical component, is provided, covering areas from physiology and anatomy of the spinal cord, neuropathology of the SCI, current clinical options, neuronal plasticity after SCI and a variety of promising neuroprotective, cell-based and combinatorial therapeutic approaches that have recently moved, or are close to clinical testing.
Journal ArticleDOI
Recruitment of Beneficial M2 Macrophages to Injured Spinal Cord Is Orchestrated by Remote Brain Choroid Plexus
Ravid Shechter,Omer Miller,Gili Yovel,Neta Rosenzweig,Anat London,Julia Ruckh,Ki-Wook Kim,Eugenia Klein,Vyacheslav Kalchenko,Peter Bendel,Sergio A. Lira,Steffen Jung,Michal Schwartz +12 more
TL;DR: It is demonstrated that the route of monocyte entry to central nervous system provides an instructional environment to shape their function, and the homing of proinflammatory and anti-inflammatory macrophages to traumatized spinal cord was distinctly regulated.
Journal ArticleDOI
Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury
Osahiko Tsuji,Kyoko Miura,Yohei Okada,Kanehiro Fujiyoshi,Masahiko Mukaino,Narihito Nagoshi,Kazuya Kitamura,Gentaro Kumagai,Makoto Nishino,Shuta Tomisato,Hisanobu Higashi,Toshihiro Nagai,Hiroyuki Katoh,Kazuhisa Kohda,Yumi Matsuzaki,Michisuke Yuzaki,Eiji Ikeda,Eiji Ikeda,Yoshiaki Toyama,Masaya Nakamura,Shinya Yamanaka,Hideyuki Okano +21 more
TL;DR: The directed neural differentiation of murine iPS cells is shown and it is suggested that pre-evaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.
Journal ArticleDOI
TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord.
Antje Kroner,Andrew D. Greenhalgh,Juan G. Zarruk,Rosmarini Passos dos Santos,Matthias Gaestel,Samuel David +5 more
TL;DR: It is shown that TNF prevents phagocytosis-mediated conversion from M1 to M2 cells in vitro and in vivo in spinal cord injury (SCI), and transplantation experiments show that increased loading of M2 macrophages with iron induces a rapid switch from M2 to M1 phenotype.
References
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TL;DR: The data indicate that the BBB scale is a valid and predictive measure of locomotor recovery able to distinguish behavioral outcomes due to different injuries and to predict anatomical alterations at the lesion center.
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Pauline Dergham,Benjamin Ellezam,Charles Essagian,Hovsep Avedissian,William D. Lubell,Lisa McKerracher +5 more
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