Delayed applications of L1 and chondroitinase ABC promote recovery after spinal cord injury.
Standard
Delayed applications of L1 and chondroitinase ABC promote recovery after spinal cord injury. / Lee, Han Kyu; Bian, Shan; Jakovcevski, Igor; Wu, Bin; Irintchev, Andrey; Schachner, Melitta.
in: J NEUROTRAUM, Jahrgang 29, Nr. 10, 10, 2012, S. 1850-1863.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Delayed applications of L1 and chondroitinase ABC promote recovery after spinal cord injury.
AU - Lee, Han Kyu
AU - Bian, Shan
AU - Jakovcevski, Igor
AU - Wu, Bin
AU - Irintchev, Andrey
AU - Schachner, Melitta
PY - 2012
Y1 - 2012
N2 - The inhibitory environment of the injured spinal cord is an obstacle to functional recovery and axonal regeneration in adult mammals. We had previously shown that injection of adeno-associated virus (AAV) encoding the L1 cell adhesion molecule (AAV-L1) at the time of acute thoracic compression injury of adult mice promotes locomotor recovery, which is associated with ameliorated astrogliosis and improved axonal regeneration in the lumbar spinal cord. In the present study, we investigated whether delayed injection of AAV-L1, chondroitinase ABC (Chase), or the combination of the two agents into the mouse spinal cord 3 weeks after injury would also lead to improved recovery. The Basso Mouse Scale showed enhanced locomotor recovery 12 weeks after application of the agents in all treatment groups compared to the control group that was injected with AAV encoding green fluorescent protein (AAV-GFP). Investigation of hindlimb function using single-frame motion analysis revealed, however, that L1 overexpression, but not injection of Chase, improved voluntary movements without body weight support, whereas injection of Chase, but not L1 overexpression, enhanced body weight support during stepping. Mice with the combined application of AAV-L1 and Chase showed improvement in both parameters. Enhanced motor recovery after combined application correlated with increased densities of cholinergic and GABAergic terminals at motoneuronal cell bodies, and of lamina-specific glutamatergic sensory afferents 15 weeks after injury, indicating enhanced synaptic rearrangements in the lumbar spinal cord below the lesion site. These findings suggest that L1 overexpression combined with Chase application may contribute to the treatment of sub-chronic spinal cord injury.
AB - The inhibitory environment of the injured spinal cord is an obstacle to functional recovery and axonal regeneration in adult mammals. We had previously shown that injection of adeno-associated virus (AAV) encoding the L1 cell adhesion molecule (AAV-L1) at the time of acute thoracic compression injury of adult mice promotes locomotor recovery, which is associated with ameliorated astrogliosis and improved axonal regeneration in the lumbar spinal cord. In the present study, we investigated whether delayed injection of AAV-L1, chondroitinase ABC (Chase), or the combination of the two agents into the mouse spinal cord 3 weeks after injury would also lead to improved recovery. The Basso Mouse Scale showed enhanced locomotor recovery 12 weeks after application of the agents in all treatment groups compared to the control group that was injected with AAV encoding green fluorescent protein (AAV-GFP). Investigation of hindlimb function using single-frame motion analysis revealed, however, that L1 overexpression, but not injection of Chase, improved voluntary movements without body weight support, whereas injection of Chase, but not L1 overexpression, enhanced body weight support during stepping. Mice with the combined application of AAV-L1 and Chase showed improvement in both parameters. Enhanced motor recovery after combined application correlated with increased densities of cholinergic and GABAergic terminals at motoneuronal cell bodies, and of lamina-specific glutamatergic sensory afferents 15 weeks after injury, indicating enhanced synaptic rearrangements in the lumbar spinal cord below the lesion site. These findings suggest that L1 overexpression combined with Chase application may contribute to the treatment of sub-chronic spinal cord injury.
KW - Animals
KW - Female
KW - Treatment Outcome
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Drug Administration Schedule
KW - Chondroitin ABC Lyase/pharmacology/therapeutic use
KW - Genetic Therapy/methods
KW - Nerve Regeneration/drug effects/genetics
KW - Neural Cell Adhesion Molecule L1/genetics
KW - Recovery of Function/drug effects/genetics
KW - Spinal Cord Injuries/drug therapy/enzymology/physiopathology
KW - Animals
KW - Female
KW - Treatment Outcome
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Drug Administration Schedule
KW - Chondroitin ABC Lyase/pharmacology/therapeutic use
KW - Genetic Therapy/methods
KW - Nerve Regeneration/drug effects/genetics
KW - Neural Cell Adhesion Molecule L1/genetics
KW - Recovery of Function/drug effects/genetics
KW - Spinal Cord Injuries/drug therapy/enzymology/physiopathology
M3 - SCORING: Journal article
VL - 29
SP - 1850
EP - 1863
JO - J NEUROTRAUM
JF - J NEUROTRAUM
SN - 0897-7151
IS - 10
M1 - 10
ER -
