Neuronal Circuit Remodeling in the Contralateral Cortical Hemisphere during Functional Recovery from Cerebral Infarction

Recent advances in functional imaging of human brain activity in stroke patients, e.g., functional magnetic resonance imaging, have revealed that cortical hemisphere contralateral to the infarction plays an important role in the recovery process. However, underlying mechanisms occurring in contralateral hemisphere during functional recovery have not been elucidated. We experimentally induced a complete infarction of somatosensory cortex in right hemisphere of mice and examined the neuronal changes in contralateral (left) somatosensory cortex during recovery. Both basal and ipsilateral somatosensory stimuli-evoked neuronal activity in left (intact) hemisphere transiently increased 2 d after stroke, followed by an increase in the turnover rate of usually stable mushroom-type synaptic spines at 1 week, observed by using two-photon imaging in vivo. At 4 weeks after stroke, when functional recovery had occurred, a new pattern of electrical circuit activity in response to somatosensory stimuli was established in intact ipsilateral hemisphere. Thus, the left somatosensory cortex can compensate for the loss of the right somatosensory cortex by remodeling neuronal circuits and establishing new sensory processing. This finding could contribute to establish the effective clinical treatments targeted on the intact hemisphere for the recovery of impaired functions and to achieve better quality of life of patients.

[1]  Richard S. J. Frackowiak,et al.  The functional anatomy of motor recovery after stroke in humans: A study with positron emission tomography , 1991, Annals of neurology.

[2]  Ian Q Whishaw,et al.  Evidence for bilateral control of skilled movements: ipsilateral skilled forelimb reaching deficits and functional recovery in rats follow motor cortex and lateral frontal cortex lesions , 2004, The European journal of neuroscience.

[3]  Lorraine O. Ramig,et al.  Translating principles of neural plasticity into research on speech motor control recovery and rehabilitation. , 2008, Journal of speech, language, and hearing research : JSLHR.

[4]  F. Engert,et al.  Dendritic spine changes associated with hippocampal long-term synaptic plasticity , 1999, Nature.

[5]  Rüdiger J. Seitz,et al.  Post-lesional cerebral reorganisation: Evidence from functional neuroimaging and transcranial magnetic stimulation , 2006, Journal of Physiology-Paris.

[6]  T. Lømo,et al.  Patterns of activation in a monosynaptic cortical pathway: The perforant path input to the dentate area of the hippocampal formation , 2004, Experimental Brain Research.

[7]  T. Murphy,et al.  Extensive Turnover of Dendritic Spines and Vascular Remodeling in Cortical Tissues Recovering from Stroke , 2007, The Journal of Neuroscience.

[8]  D. Corbett,et al.  Efficacy of Rehabilitative Experience Declines with Time after Focal Ischemic Brain Injury , 2004, The Journal of Neuroscience.

[9]  S. Carmichael,et al.  Plasticity of Cortical Projections after Stroke , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[10]  C. Calautti,et al.  Functional Neuroimaging Studies of Motor Recovery After Stroke in Adults: A Review , 2003, Stroke.

[11]  T. Neumann-Haefelin,et al.  Cellular correlates of neuronal hyperexcitability in the vicinity of photochemically induced cortical infarcts in rats in vitro , 1995, Neuroscience Letters.

[12]  R. Racine,et al.  Changes in field potentials and membrane currents in rat sensorimotor cortex following repeated tetanization of the corpus callosum in vivo. , 1998, Cerebral cortex.

[13]  B. Johansson Brain plasticity and stroke rehabilitation. The Willis lecture. , 2000, Stroke.

[14]  K. Zilles,et al.  Neuronal Hyperexcitability and Reduction of GABAA-Receptor Expression in the Surround of Cerebral Photothrombosis , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[16]  R. Woods,et al.  Recovery from wernicke's aphasia: A positron emission tomographic study , 1995, Annals of neurology.

[17]  B. Johansson,et al.  Neuronal Plasticity and Dendritic Spines: Effect of Environmental Enrichment on Intact and Postischemic Rat Brain , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  Yue Cao,et al.  Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. , 1998, Stroke.

[19]  Keith D. White,et al.  Functional MRI of Language in Aphasia: A Review of the Literature and the Methodological Challenges , 2007, Neuropsychology Review.

[20]  O W Witte,et al.  Induction of bilateral plasticity in sensory cortical maps by small unilateral cortical infarcts in rats , 2003, The European journal of neuroscience.

[21]  N. Ward,et al.  Future perspectives in functional neuroimaging in stroke recovery. , 2007, Europa medicophysica.

[22]  G. Shepherd,et al.  Current-density analysis of summed evoked potentials in opossum prepyriform cortex. , 1973, Journal of neurophysiology.

[23]  G. Ellis‐Davies,et al.  Structural basis of long-term potentiation in single dendritic spines , 2004, Nature.

[24]  K. Zilles,et al.  Changes in GABAA and GABAB receptor binding following cortical photothrombosis: a quantitative receptor autoradiographic study , 1999, Neuroscience.

[25]  K. Svoboda,et al.  Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. , 1999, Science.

[26]  N. Kasthuri,et al.  Long-term dendritic spine stability in the adult cortex , 2002, Nature.

[27]  B. Rosen,et al.  A functional MRI study of subjects recovered from hemiparetic stroke. , 1997, Stroke.

[28]  B. Johansson,et al.  Brain plasticity and stroke rehabilitation , 2008 .

[29]  T. Murphy,et al.  Imaging the Impact of Cortical Microcirculation on Synaptic Structure and Sensory-Evoked Hemodynamic Responses In Vivo , 2007, PLoS biology.

[30]  C. Nicholson,et al.  Theory of current source-density analysis and determination of conductivity tensor for anuran cerebellum. , 1975, Journal of neurophysiology.

[31]  T. Mittmann,et al.  Ischaemia‐induced Long‐term Hyperexcitability in Rat Neocortex , 1995, The European journal of neuroscience.

[32]  S N Davies,et al.  Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. , 1988, Science.

[33]  J. Nabekura,et al.  Resting Microglia Directly Monitor the Functional State of Synapses In Vivo and Determine the Fate of Ischemic Terminals , 2009, The Journal of Neuroscience.

[34]  U. Mitzdorf Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. , 1985, Physiological reviews.