Corticostriatal plasticity is restricted by myelin-associated neurite growth inhibitors in the adult rat.
After unilateral cortical lesions in neonatal rats, the spared unablated hemisphere is known to demonstrate remarkable neuroanatomical plasticity in corticofugal connectivity. This same type of structural plasticity is not seen after similar lesions in adult rats. One possibility for the lack of such a plastic response in the adult central nervous system may be the presence of myelin-associated neurite growth inhibitory proteins NI-35/NI-250. These proteins have previously been found to play a crucial role in preventing axotomized fibers from regenerating after adult rat spinal cord lesions. The aim of this study was to determine if blocking these inhibitory proteins by the application of the specific monoclonal antibody IN-1 would enhance corticostriatal plasticity from the spared hemisphere after unilateral cortical lesions in adult rats. Six- to 8-week-old Lewis rats underwent unilateral aspiration lesion of the sensorimotor cortex. Animals were immediately treated with either monoclonal antibody IN-1 or a control antibody released from hybridoma cells in Millipore filter capsules. After a survival period of 12 weeks, the opposite sensorimotor cortex was stereotaxically injected with the anterograde tracer biotinylated dextran amine, and biotinylated dextran amine-positive corticostriatal fibers were analyzed. The monoclonal antibody IN-1-treated animals showed an increase in corticostriatal fibers in the dorsolateral striatum contralateral to the injection site compared with control antibody-treated animals or normal controls, indicating a specific sprouting response in the deafferented zone. These results support the idea that through blockade of myelin-associated neurite inhibitory proteins, lesion-induced corticofugal plasticity is possible even in the adult central nervous system.
Kartje
G L
GL
Neurology Service, Edward Hines Jr Veteran Affairs Hospital, Hines, IL 60141, USA.
Schulz
M K
MK
Lopez-Yunez
A
A
Schnell
L
L
Schwab
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology*; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D008297:Male; D009186:Myelin Sheath / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal