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4 Patologie 46 AVC

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  • Recuperare, medicin fizic i balneologie

    Dan NemeDaniel Popa,Raluca Cotulbea, Alina Totorean, Armand Gogulescu, Andrea Ni, Merima Jurici, Elena Amrici, Virgil Luca, Cristina Cristea, Oana Bereteu, Roxana Onofrei, Corina Dobrescu

  • Accidentul vascular cerebral

  • MODULAREA PLASTICITII CREIERULUI STRATEGIE NOVATOARE N REABILITAREA ACCIDENTULUI CEREBRAL

  • What is stroke ?

  • Seth Finklestein, M.D., ViaCell Neuroscience, october, 2002

  • Spasticitatea (piramidal)

  • Seth Finklestein, M.D., ViaCell Neuroscience, october,2002

  • The brain recovers by Rewiring

    Seth Finklestein, M.D., ViaCell Neuroscience, october,2002

  • Brain Recovers by endogenous stem cell proliferation

    Seth Finklestein, M.D., ViaCell Neuroscience, october,2002

  • Funcia=engramele

  • NeuroplasticitateaTermenul de plasticitate neuronal a fost folosit pentru a descrie modificrile morfologice i funcionale remanente ale neuronului adult.

    n timpul executrii activitilor motorii s-au demonstrat modificri remarcabile ale cortexului motor, date de ageni farmacologici i de modificri ale SNC i SNP.

    Lumy Sawaki, Department of Neurology, Program in rehabilitation, Salem, USA

  • NeuroplasticityNeuronal connections and cortical maps are continuously remodeled by our experience.

    Experimental focal cortical lesions induce changes in adjacent cortex and in the contralateral hemisphere.

    Neuroimaging studies in stroke patients indicate altered poststroke activation patterns, which suggest some functional reorganization.

    Reorganization may be the principle process responsible for recovery of function after stroke, but what are the limits, and to what extent can postischemic intervention facilitate such changes?

    Barbro B. Johansson, MD, PhD, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden.

  • Neuroplasticity & Regeneration

    General principles

    Habituation

    Learning & Memory

    Recovery from injury

  • General principlesHabituation -Repeated exposure to stimulus temporarily reduces response activity

    -Animals reared or housed as adults in complex environments with access to various toys and activities develop more dendritic branching and more synapses per neuron and have higher gene expression for trophic factors than animals housed individually or in small groups in standard cages.

    Barbro B. Johansson, MD, PhD, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden.

  • General principlesLearning & Memory -Synapses used often are strengthened

    - Stronger synapses are retained

    - Potentiation: a weak synapse is strengthened if it is activated along with a stronger synapse

    - Generalization: if a new stimulus is similar to a familiar stimulus, the well-practiced pattern of neural activity is more likely to be activated

  • General principles Recovery from injury -Neuronal death if sufficient damage

    -A neuron receiving much of its input from a dying neuron may also die

    -Local changes after loss of a presynaptic neuron may lead to collateral sprouting & formation of anomalous synapses

    -If an axon is injured, the neuron may or may not die; axonal regeneration may occur

  • Factors related to recovery

    - Axonal regeneration in the PNS may involve re-growth of the axon over substantial distances

    - Once re-growth to the vicinity of the target, the axon must still form appropriate connections

    - In the CNS, collateral sprouting is more common (0.5mm - 10mm?)

  • Functional reorganization- PNS is relatively hardwired, so source of functional change is in CNS

    - Brainstem & subcortical systems also are hardwired

    - Most believe plastic cortical systems permit functional recovery

  • Possible Mechanisms Behind Brain Plasticity Synaptic plasticity in cortical horizontal connections has been proposed to underlie cortical map reorganization

    Glutamate, the main excitatory neurotransmitter, plays a crucial role.

    Aminobutyric acid (GABA)-A receptor antagonists can facilitate LTP induction in neocortical synaptic systems, and the induction can be blocked by GABA-A receptor agonists

    Transmitters released by the diffuse neuromodulatory systems originating in locus coeruleus (noradrenalin), nucleus basalis (acetylcholine), lateral tegmentum (dopamine), and raphe nuclei (serotonin) may modify the process

    Nitric oxide is another candidate for dynamic modulation of cerebral cortex synaptic function.

    There is increasing evidence that astrocytes take an active part in synaptic plasticity

    Barbro B. Johansson, MD, PhD, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden.

  • Factorii neurotroficiUltimul deceniu al secolului incheiat a fost pe buna dreptate numit decada neurobiologiei si a reprezentat un imens pas inainte in acest fascinant domeniu.

    In acest context factorii neurotrofici se afla in frontul cercetarilor stiintifice datorita importantei teoretice si mai ales numeroaselor perspective aplicative.

  • Factorii neurotrofici Factorii neurotrofici sunt polipeptide cu rol reglator si fac parte din grupul factorilor de crestere.- FACTORII DE CRESTERE

    - FACTORII DE NECROZA TUMORALA

    - INTERFERONIICITOKINELEINTERLEUKINLE

  • Factorii neurotrofici Factorii neurotrofici sunt secretati in mod natural de catre toate tipurile de celule ale tesutului nervos cat si de catre alte tesuturi.

    Sistemul nervos produce factori neurotrofici si raspunde la actiunea acestora.

  • Rolul factorilor neurotroficiFactorii neurotrofici au rol in:

    Dezvoltarea ontogenetica controleaza proliferarea celulara si diferentierea (exprimarea fenotipului de mediator si a canalelor ionice, cresterea prelungirilor).

    Promovarea supravietuirii naturale(in lipsa agentilor nocivi) pe tot parcursul vietii si mentinerea fenotipului.

  • Rolul factorilor neurotroficiFactorii neurotrofici au rol in:

    Cresterea rezistentei celulelor nervoase la actiunea agentilor nocivi(hipoxia, ischemia, hipoglicemia, excitotoxicitatea, substantele toxice, traumatismele)

    Plasticitatea si activitatea sinaptica(deci si in procesul de invatare)

    Cercetarea experimentala, respectiv clinica au demonstrat existenta unor efecte terapeutice impresionante ale factorilor neurotrofici.

  • RECUNOASTEREA PUBLICA A IMPORTANTEI ACESTUI DOMENIU A AVUT LOC IN 1986 PRIN ACORDAREA PREMIULUI NOBEL CERCETATORILOR

    RITA LEVI-MONTALCINI SI STANLEY COHEN

    PENTRU LUCRARILE LOR DE PIONIERAT IN DOMENIUL FACTORULUI DE CRESTERE AL NERVILOR (NGF) SI FACTORULUI DE CRESTERE EPIDERMIC.

  • Factorii neurotroficiKrutgen si col.(1997) au efectuat o analiza detaliata a functiei diverselor regiuni ale moleculei de NGF prin deletarea pas cu pas a aminoacizilor si prin mutatii punctiforme.Au constatat ca regiunea din NGF formata din aminoacizii 111-115 situata la extremitatea COOH este cea care se leaga de receptorul TrK-A, determina fosforilarea tirozinei din constitutia receptorului si in final diferentierea neuronilor (cresterea prelungirilor) .

    Constatarea are o deosebita importanta practica pentru ca NGF fiind o proteina cu greutate moleculara mare nu trece prin bariera hematoencefalica.

  • Efectele NGFIn cursul dezvoltarii ontogenetice sunt generati mult mai multi neuroni decat sunt necesari in sistemul nervos matur.

    Exista o perioada in care mai mult de jumatate din toti neuronii mor prin apoptoza.

    Supravietuirea selectiva numai a unei anumite parti din neuroni se explica prin competitia prelungirilor celulelor nervoase pentru o cantitate limitata de factor neurotrofic elaborat de tesuturile tinta.

    Neuronii care nu obtin factor trofic mor.

    Pe parcursul vietii, NGF regleaza gradul de ramificare al prelungirilor neuronale, determinand viteza si gradul deregenerare al celulelor nervoase dependente de el.

    Exista si un model experimental.

  • Efectele NGF Kawaja 1997 si Come 1988 au generat o linie de soareci transgenici la care o gena NGF a fost plasata sub controlul promotorului pentru gena proteinei fibrilare gliala acida.

    La aceste animale NGF era exprimat in cantitati crescute in SNC in astrocite. Hiperexprimarea NGF a determinat o crestere aberanta a fibrelor simpatice si senzitive.

    In cerebel s-a constatat o patrundere puternica de noi fibre simpatice si un plex dens de axoni de origine senzitiva.

    Densitatea acestor axoni a crescut impresionant cu varsta. Fibrele senzitive aberante din cerebelul transgenic isi aveau originea in ganglionul trigeminal si ganglionii spinali din regiunea cervicala superioara.

  • NGF moduleaza exprimarea fenotipului de mediatorIn experiente pe culturi de neuroni embrionariizolati din ariilebogate in neuroni colinergici s-aconstatat ca introducerea NGF inmediul decultura determina intensificareaactivitatiicolinoacetiltransferazei (ChAT).

    Cresterea colinoacetiltransferazei s-a acompaniat cu cresterea cantitatii de acetilcolina din neuronii septali.

    Infuzia intraventriculara continua de NGF creste nivelulacetilcolintransferazei si la sobolanii adulti.

  • Familia NeurotrofinelorNGF actioneaza specific asupra unui numar redus de populatii de neuroni: neuronii simpatici, neuronii senzitiv derivati din cresterea neurala (gglspinali) si neuronii colinergici din regiunea bazala si anterioara a creierului.

    Specificiatea neuronala limitata a NGF a determinat pe cercetatori sa emita ipoteza existentei si a altor factori neurotrofici cu specificitati neuronale diferite.

    S-a cons