From Animal Model to Bedside Method

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From Animal Model to Bedside Method basic and
translational research in TBI rehabilitation

• Jesper Mogensen
• Head of UCN (The Unit for Cognitive
  Neuroscience), Dept. of Psychol., University of
  Copenhagen
• Director of ReCBIR (Research Centre for Brain
  Injury Rehabilitation)

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Brain injury
- and rehabilitation
Animal Models and what can be gained
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Supporting recovery and training
The mechanisms of functional recovery
Pharmacology
Activation/Stimulation
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The mechanisms of functional recovery
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FULL RECOVERY IN SPITE OF MISSING BRAIN
STRUCTURES (ALLOCENTRIC PLACE LEARNING)
FFPFC
PFC
FF
sham
Mogensen et al. Brain Research Bulletin, 2004
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Regional specialization of the brain
localization of function
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LOCALIZATION
OR
RECOVERY?
OR?
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ALLOCENTRIC PLACE LEARNING
Mogensen et al. Brain Research Bulletin, 2004
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NUMBER OF SESSIONS TO CRITERION
Mogensen, J., Lauritsen, K.T., Elvertorp,S.,
Hasman, A., Moustgaard, A. Wörtwein, G. Place
learning and object recognition by rats
subjected to transection of the fimbria-fornix
and/or ablation of the prefrontal cortex. Brain
Research Bulletin, 2004, 63, 217-236.
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Different Solution Strategies

• Mogensen, J., Lauritsen, K.T., Elvertorp, S.,
  Hasman, A., Moustgaard, A. Wörtwein, G. Place
  learning and object recognition by rats subjected
  to transection of the fimbria-fornix and/or
  ablation of the prefrontal cortex. Brain Research
  Bulletin, 2004, 63, 217-236

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SHIFT in the NEURAL SUBSTRATE
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FFPFC
PFC
EGOCENTRIC PLACE LEARNING IN RATS SUBJECTED TO
LESIONS OF HIPPOCAMPUS AND/OR THE PREFRONTAL
CORTEX
FF
sham
Mogensen et al., 2005
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EGOCENTRIC PLACE LEARNING - NUMBER OF
SESSIONS TO CRITERION
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COMPARISON BETWEEN ALLOCENTRIC AND EGOCENTRIC
PLACE LEARNING
ALLOCENTRIC
EGOCENTRIC
J
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SPATIAL DELAYED ALTERNATION IN RATS SUBJECTED
TO LESIONS OF HIPPOCAMPUS AND/OR THE
PREFRONTAL CORTEX
Mogensen et al., 2007
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SPATIAL DELAYED ALTERNATION - NUMBER OF
SESSIONS TO CRITERION
Mogensen et al., 2007
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SPATIAL DELAYED ALTERNATION
Mogensen et al., 2007
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PHENOMENA OF POSTTRAUMATIC RECOVERY
1. MODIFICATION OF DEGREE OF CONTRIBUTION TO TASK MEDIATION BY INDIVIDUAL STRUCTURES Some structures exhibit increased or decreased levels of contribution to task mediation
2. TASK-DEPENDENT AND DISSIMILAR NEURAL SUBSTRATES After a given lesion the functional recovery of various cognitive tasks is mediated by unique and dissimilar neural substrates
3. APPLICATION OF NEW COGNITIVE STRATEGIES The fully posttraumatically recovered individuals solve the task by applying new strategies that are dissimilar to those applied pretraumatically
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II
BEHAVIOUR X
NEURAL SUBSTRATES
I
IX
XV
ALGORITHMIC STRATEGIES
VIII
XIV
AS C
XIII
AS A
III
VII
X
IV
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ELEMENTARY FUNCTIONS
XII
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UNDERLYING NEURAL MECHANISMS
Brain structure ?
XI
EF1
EF2
EF3
EF4
EF5
EF6
EF7
EF8
EF9
EF10
EF11
EF12
EF13
EF14
EF15
Brain structure ß
UNDERLYING COGNITIVE MECHANISMS
Brain structure a
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- IMPLICATIONS?
The REF-model
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GENERALIZATION?
of test results
and of training!
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Supporting recovery and training
Preserving originally spared parts of the brain
reducing secondary and tertiary degeneration
Promoting relevant, synaptic reorganization
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BDNF (Brain-Derived Neurotrophic Factor)
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TROPHIC FACTORS
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NEUROGENESIS IN THE ADULT BRAIN
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Supporting recovery and training
Pharmacology
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Pharmacologically supported functional recovery
effects of Erythropoietin (EPO)
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EPO and BDNF
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7 days
30 days
Interactions
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Glutamate
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Glutamate - PIMSD
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Supporting recovery and training
Activation/Stimulation
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Activation/Stimulation as a Therapeutic Method in
Brain Injury
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BDNF
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Early or late ?
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LATE !
But
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Activation/Stimulation as a Therapeutic Method in
Brain Injury
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Forced or voluntary ?
Stress ?
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VOLUNTARY !
But
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Activation/Stimulation as a Therapeutic Method in
Brain Injury
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The role of stress
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THE DYNAMIC BRAIN HOPES AND CHALLENGES
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In animal models and clinical work Lets go
directly for the solutions!THANK YOU !