Effect of brain-derived neurotrophic factor treatment and forced arm use on functional motor recovery after small cortical ischemia.
OBJECTIVE
Both the administration of growth factors and physical therapy such as forced arm use (FAU) are promising approaches to enhance recovery after stroke. We explored the effects of these therapies on behavioral recovery and molecular markers of regeneration after experimental ischemia.


METHODS
Rats were subjected to photothrombotic ischemia: sham (no ischemia), control (ischemia), brain-derived neurotrophic factor (BDNF; ischemia plus BDNF, 20 microg), and FAU (ischemia plus FAU, 1-sleeve plaster cast ipsilateral limb). Animals survived 1 or 6 weeks and underwent behavioral testing (Rotarod, beam balance, adhesive removal, plantar test, neuroscore). After the rats were killed, brain sections were immunostained for semiquantitative analysis of MAP1B, MAP2, synaptophysin, GFAP expression, and quantification of infarct volumes.


RESULTS
Infarct volumes were not different between the groups 1 or 6 weeks after ischemia. BDNF-treated animals had better functional motor recovery (Rotarod, beam balance, neuroscore) compared with all other groups (P<0.05). There was no significant adverse effect of early FAU treatment on motor recovery, although sensorimotor function (adhesive removal test) was impaired (P<0.05). There were no differences between groups as measured by nociception of the left and right forepaw (plantar test). BDNF treatment transiently induced MAP1B expression in the ischemic border zone and synaptophysin expression within the contralateral cortex 6 weeks after ischemia (P<0.05). Both BDNF and FAU reduced astrogliosis compared with controls (P<0.05).


CONCLUSIONS
Postischemic intravenous BDNF treatment improves functional motor recovery after photothrombotic stroke and induces widespread neuronal remodeling. Early FAU treatment after stroke does not increase infarct size, impairs sensorimotor function, but leaves motor function unchanged. Postischemic astrogliosis was reduced by both treatments.
Schäbitz
W-R
WR
Department of Neurology, University of Heidelberg, INF 400, 69120 Heidelberg, Germany. wolf_schaebitz@med.uni-heidelberg.de
Berger
C
C
Kollmar
R
R
Seitz
M
M
Tanay
E
E
Kiessling
M
M
Schwab
S
S
Sommer
C
C
D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000473:pathology; D003131:Combined Modality Therapy; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000276:immunology; D007103:Immobilization; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000276:immunology; D009043:Motor Activity; D009416:Nerve Regeneration; D026741:Physical Therapy Modalities; D051381:Rats; D017208:Rats, Wistar; D016708:Synaptophysin / Q000032:analysis / Q000276:immunology; D034941:Upper Extremity
D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D016708:Synaptophysin; C085284:microtubule-associated protein 1B