cel glia-1

CLULAS GLIALES DEL SISTEMA NERVIOSO !

Introduccin a las clulas de la gla

http://www.youtube.com/watch?v=YYiyhcZCNxc&feature=related

capilar!

astrocito!neurona!Gap junction (GJ)!Oligodendrocito!

Mielina!

ramificacin!astrocito!

ramificacin!astrocito!

. Microgliales

Clasificacin de las clulas del sistema nervioso"

- Clulas gliales"

Sistema Nervioso Central (CNS)

- Neuronas

. Macrogliales Astrocitos Oligodendrocitos

Clasificacin de las clulas del sistema nervioso"

- Clulas gliales"

Sistema Nervioso Perifrico (PNS)"

- Neuronas

. Clulas de Schwann mielinizantes "

. Clulas de Schwann no mielinizantes "

CARACTERISTICAS Y FUNCIONES !

DE CADA TIPO CELULAR!

ASTROCITOS"Caracterstica diferencial: GFAP, protena fibrilar cida "de la gla. Protena del citoesqueleto."Funciones:"

Gua de las neuronas durante la migracin"Colaboran en la regeneracin neuronal"Inducen la formacin de la BHE"

Soporte metablico de las neuronas"

Mantienen la homeostasis del medio extracelular"Presentan excitabilidad en respuesta a la actividad neuronal"Recaptan neurotransmisores"

Clulas madre del cerebro adulto"Colaboran en la formacin de sinapsis"

mouse!

human!

astrocytes! neurons!

Gua y reparacin neuronal Molculas de adhesin

Expresadas en la superficie N-CAM N-cadherina Liberadas al medio extracelular Laminina

Molculas que repelen axones Proteoglicanos condroitin sulfato dermatan sulfato.

Otros factores neurotrficos: ej: cido oleico

N-caderinas!

N-CAM!

Condroitn sulfato!

laminina!

N-cadherina!

+ CSPG!

PTP-/-!

http://www.youtube.com/watch?v=R9mjl6F-Lyo

Transplante de glia envolvente del bulbo olfativo:

No poner

Spinal Cord. 2009 Dec;47(12):887-95. Epub 2009 Jun 2.!

Autologous olfactory [corrected] mucosal transplant in chronic spinal cord injury: an Indian Pilot Study.

Chhabra HS, Lima C, Sachdeva S, Mittal A, Nigam V, Chaturvedi D, Arora M, Aggarwal A, Kapur R, Khan TA.

Spine Service, Indian Spinal Injuries Center, Vasant Kunj, New Delhi, India. [email protected]

STUDY DESIGN: Prospective Pilot Study.

OBJECTIVES: To determine the safety and feasibility of autologous olfactory mucosal transplantation into the spinal cord in chronic spinal cord injured using the technique developed by Carlos Lima et al.

SETTING: Spinal Injury Center, New Delhi.

METHODS: Five chronic, motor complete, traumatic spinal cord injury (SCI) patients with neurological level C5-T12 underwent the procedure. Participants were assessed at baseline and at 6 monthly intervals. Safety and tolerability were evaluated through monitoring for any adverse events and tests including magnetic resonance imaging (MRI) evaluation. Efficacy assessment was done through neurological, functional and psychological evaluation, electrophysiological studies and urodynamics.

RESULTS: Surgery was tolerated well by all American Spinal Injury Association (ASIA) Impairment Scale (AIS) A participants. The only AIS B participant lost sensory scores significantly after surgery but is gradually regaining it. MRI evaluation revealed a syrinx in one participant and increase in length of myelomalacia in four participants. There were no other adverse findings on MRI evaluation. There was no significant improvement in any of the neurological, electrophysiological or urodynamic efficacy variables. Statistically significant improvement was seen in functional scores as evaluated by Spinal Cord Independence Measure, Beck Depression Inventory scores and life impact scores on International Spinal Cord Injury Scale.

CONCLUSIONS: The procedure is relatively safe and feasible in AIS A participants with thoracic level injuries at 18 month follow-up. No efficacy could be demonstrated which could be attributed to the procedure.

Neurorehabil Neural Repair. 2010 Jan;24(1):10-22. Epub 2009 Sep 30. Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury.

Lima C, Escada P, Pratas-Vital J, Branco C, Arcangeli CA, Lazzeri G, Maia CA, Capucho C, Hasse-Ferreira A, Peduzzi JD.

Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal. [email protected]

Abstract

BACKGROUND/OBJECTIVE: Basic science advances in spinal cord injury (SCI) are leading to novel clinical approaches. The authors report a prospective, uncontrolled pilot study of the safety and outcomes of implanting olfactory mucosal autografts (OMA) in 20 patients with chronic, sensorimotor complete or motor complete SCI.

METHODS: Seven paraplegic and 13 tetraplegic subjects (17 men and 3 women; 19-37 years old) who sustained a traumatic SCI 18 to 189 months previously (mean = 49 months) were enrolled. Preoperative rehabilitation that emphasized lower extremity stepping using either overground walking training or a robotic weight-supported treadmill training was provided for 25 to 39 hours per week for a median of 4 months at 3 sites. No change in ASIA Impairment Scale (AIS) motor scores for the lower extremities or AIS grades of completeness was found. OMAs were transplanted into 1.3- to 4-cm lesions at C4-T12 neurological levels after partial scar removal. Therapy was continued postoperatively. Preoperative and postoperative assessments included AIS scores and classification, electromyography (EMG) of attempted voluntary contractions, somatosensory evoked potentials (SSEP), urodynamic studies with sphincter EMG, spinal cord magnetic resonance imaging (MRI), and otolaryngology and psychology evaluations. The Functional Independence Measure (FIM) and Walking Index for Spinal Cord Injury (WISCI) were obtained in 13 patients.

RESULTS: All patients survived and recovered olfaction. One patient was rehospitalized for aseptic meningitis. Minor adverse events occurred in 4 others. The mean duration of follow-up was 27.7 months (range = 12-45 months). By MRI, the lesion site was filled in all patients with no neoplastic overgrowth or syringomyelia. AIS grades improved in 11 of 20 patients, 6 (A --> C), 3 (B --> C), and 2 (A --> B), and declined in 1 (B --> A). Improvements included new voluntary EMG responses (15 patients) and SSEPs (4 patients). Scores improved in the FIM and WISCI (13/13 tested), and urodynamic responses improved in 5 patients.

CONCLUSION: OMA is feasible, relatively safe, and possibly beneficial in people with chronic SCI when combined with postoperative rehabilitation. Future controlled trials may need to include a lengthy and intensive rehabilitation arm as a control.

Treatment of Rat Spinal Cord Injury with the Neurotrophic Factor Albumin-Oleic Acid: Translational Application for Paralysis, Spasticity and Pain

Gerardo Avila-Martin, Iriana Galan-Arriero, Julio Gomez-Soriano, Julian Taylor!Hospital Nacional de Parapljicos SESCAM Toledo, SPAIN

Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following A-OA treatment, mediated via demonstrated endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain.

PLoS One. 2011;6(10):e26107. Epub 2011 Oct 26."

Shen et al., Science 2009: 592-596!

+ CSPG!

PTP-/-!

Reactive astrocytes protect tissue and preserve function after spinal cord injury Faulkner et al. J Neurosci. 2004 Mar 3;24(9):2143-55.

Lesin de la mdula espinal!!longitudinal !!transversal!

Consecuencias de la eliminacin! de la gliosis reactiva!

Modelo de eliminacin de gliosis reactiva:!

Ratones transgnicos!HSVtk bajo el promotor de GFAP!

administraccin de GCV: muerte de las clulas con HSVtk y proliferativas!

No incremento GFAP!No incremento BrdU!

No hay gliosis reactiva!

Falla la reparacin de la BHE!

Aumento de la infiltracin !de leucocitos (inflamacin)!

prdida de neuronas (NeuN)!

E! E! E!

E! E! E!

X! X!

GAP JUNCTION!

Conexn

Espacio extracelular

Membrana M3

Citoplasma

Estructura de las uniones comunicantes

La Cx predominante en astrocitos es la Cx43

M4 M3

M2 M1

M4

M2

M1 M

3

M4

M3 M

2

M1

M4 M3

M2 M1

M4 M3

M2 M1

Disposicin de las Cxs formando el canal de las uniones comunicantes

HOMEOSTASIS INICA

AMORTIGUACIN ESPACIAL DE POTASIO!

N!

neurona!

astrocitos!

K+!K+! K+!K+!

K+!K+!

K+! K+!K+!K+!

K+!K+!K+!

D. Fields. Investigacin y Ciencia. Junio 2004

Tras medio siglo en un segundo plano la investigacin demuestra que las clulas de la gla intervienen en la sinapsis y desempean un papel clave en el aprendizaje y la memoria

La sinapsis tripartita

Astrocyte process!

Presynaptic!terminal!

Postynaptic!terminal!

Witcher, M.R. et al. Glia 55, 1323 (2007); Nicola J. Allen & Ben A. Barres. Nature 457, 675-677 (2009); Perea G, Navarrete M, Araque A. Trends Neurosci. 32 (2009).!

astrocitos!

N!

neurona!

N!

neurona!

ONDAS DE CALCIO

Glu!Ca 2+!

Ca 2+!Ca 2+!

Ca 2+!Ca 2+!

Ca 2+!Ca 2+!

Ca 2+!Ca 2+!

Ca 2+!Ca 2+!

Ca 2+! Ca 2+!

Ca 2+!

tiempo!

New roles for astrocytes: Regulation of synaptic transmission

Newman, Trends in Neurosciences Volume 26, Issue 10, October 2003, Pages 536-542

Astrocytes Potentiate Transmitter Release at Single

Hippocampal Synapses

Gertrudis Perea,Alfonso Araque

Science 317, 1083 (2007)!

Panatier et al., (2011) Cell 146(5) pp. 785 - 798 !

Glia Are Essential for Sensory Organ Function in C. elegans Taulant Bacaj, et al. Science 322, 744 (2008)

http://www.youtube.com/watch?v=itinDmvDEqw&feature=related!

Las clulas gliales en C. elegans!

http://www.youtube.com/watch?v=XDGd-xeo78o&feature=related!

Las clulas genio !

Los astrocitos como clulas madre en el cerebro adulto

Nature (2004) 427: 740-744!

Ki67!

GFAP!ZSV!

Ki67!

GFAP!NEUROESFERA!

oligodendrocitos!

astrocitos!

neuronas!

NEUROESFERA!

Entrevista al Prof Alvarez-Buylla !

http://www.scivee.tv/node/10083!

1. Bases fisigicas y bioqumicas de la cooperacin Metablica entre astrocitos y neuronas.

1.1.Situacin anatmica de los astrocitos.

1.2. Necesidades metablicas de las neuronas para la sntesis de neurotransmisores.

1.3. Caractersticas metablicas diferenciales de los astrocitos

2. Principales metabolitos implicados en la cooperacin metablica entre astrocitos y neuronas

1. 1. SITUACIN ANATMICA DE LOS ASTROCITOS!

Los astrocitos!rodean totalmente!los capilares cerebrales!

Constituyen una barrera fsica!entre sangre y neuronas!

Almudena Velasco. INCYL. Salamanca!

PDH!

Acetil-CoA!

piruvato!

PC!

oxalacetato!TCA!

GLU + NH 4+! Glutamina!GS!

cel glia-1

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