on February 26, 2004
Published online before print February 26, 2004, doi: 10.1161/01.STR.0000119754.85848.0D
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 15, 2003
From the Departments of Neurology (W.-R.S., C.B., R.K., M.S., E.T., S.S.) and Neuropathology (E.T., M.K.), University of Heidelberg, Heidelberg, and Division of Neuropathology, University of Ulm, Ulm (C.S.), Germany * To whom correspondence should be addressed. E-mail: wolf_schaebitz{at}med.uni-heidelberg.de.
Background and Purpose--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 µg), 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.
Accepted on December 16, 2003
Effect of Brain-Derived Neurotrophic Factor Treatment and Forced Arm Use on Functional Motor Recovery After Small Cortical Ischemia
W.-R. Schäbitz MD*;
Key words: brain-derived neurotrophic factor • cerebral ischemia • forced arm use • photothrombosis • regeneration
This article has been cited by other articles:
 |
|
 |
|
  Y. Tanaka, Y. Tozuka, T. Takata, N. Shimazu, N. Matsumura, A. Ohta, and T. Hisatsune Excitatory GABAergic Activation of Cortical Dividing Glial Cells Cereb Cortex, September 1, 2009; 19(9): 2181 - 2195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ploughman, V. Windle, C. L. MacLellan, N. White, J. J. Dore, and D. Corbett Brain-Derived Neurotrophic Factor Contributes to Recovery of Skilled Reaching After Focal Ischemia in Rats Stroke, April 1, 2009; 40(4): 1490 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Cumberland Consensus Working Group, B. Cheeran, L. Cohen, B. Dobkin, G. Ford, R. Greenwood, D. Howard, M. Husain, M. Macleod, R. Nudo, et al. The Future of Restorative Neurosciences in Stroke: Driving the Translational Research Pipeline From Basic Science to Rehabilitation of People After Stroke Neurorehabil Neural Repair, February 1, 2009; 23(2): 97 - 107. [Abstract] [PDF]
|
|
|
|
|
|
H. D. Muller, K. M. Hanumanthiah, K. Diederich, S. Schwab, W.-R. Schabitz, and C. Sommer Brain-Derived Neurotrophic Factor But Not Forced Arm Use Improves Long-Term Outcome After Photothrombotic Stroke and Transiently Upregulates Binding Densities of Excitatory Glutamate Receptors in the Rat Brain Stroke, March 1, 2008; 39(3): 1012 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimamura, N. Sato, M. Sata, H. Kurinami, D. Takeuchi, K. Wakayama, T. Hayashi, H. Iida, and R. Morishita Delayed Postischemic Treatment With Fluvastatin Improved Cognitive Impairment After Stroke in Rats Stroke, December 1, 2007; 38(12): 3251 - 3258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L Wolf Revisiting Constraint-Induced Movement Therapy: Are We Too Smitten With the Mitten? Is All Nonuse "Learned"? and Other Quandaries Physical Therapy, September 1, 2007; 87(9): 1212 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-R. Schabitz, T. Steigleder, C. M. Cooper-Kuhn, S. Schwab, C. Sommer, A. Schneider, and H. G. Kuhn Intravenous Brain-Derived Neurotrophic Factor Enhances Poststroke Sensorimotor Recovery and Stimulates Neurogenesis Stroke, July 1, 2007; 38(7): 2165 - 2172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Ito, T. Kuroiwa, J. Nagasao, E. Kawakami, and K. Oyanagi Temporal Profiles of Axon Terminals, Synapses and Spines in the Ischemic Penumbra of the Cerebral Cortex: Ultrastructure of Neuronal Remodeling Stroke, August 1, 2006; 37(8): 2134 - 2139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fisher, A. Davalos, A. Rogalewski, A. Schneider, E. B. Ringelstein, and W.-R. Schabitz Toward a Multimodal Neuroprotective Treatment of Stroke Stroke, April 1, 2006; 37(4): 1129 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shimamura, N. Sato, S. Waguri, Y. Uchiyama, T. Hayashi, H. Iida, T. Nakamura, T. Ogihara, Y. Kaneda, and R. Morishita Gene Transfer of Hepatocyte Growth Factor Gene Improves Learning and Memory in the Chronic Stage of Cerebral Infarction Hypertension, April 1, 2006; 47(4): 742 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vaynman and F. Gomez-Pinilla License to Run: Exercise Impacts Functional Plasticity in the Intact and Injured Central Nervous System by Using Neurotrophins Neurorehabil Neural Repair, December 1, 2005; 19(4): 283 - 295. [Abstract] [PDF]
|
|