Effects of physical exercise in cerebrovascular mechanisms of adaptation to altitude

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Microvascular environment plays a fundamental role in the adaptive response to increases in activity, involving an increase in energy demand. To puntual increases in demand, the response is effected by changes in local flow, but if demand remains high, angiogenic process is triggered through the formation of new capillaries from preexisting vessels. The trigger factor of angiogenesis is local neuronal hypoxia as result of increased activity, mediated by angioglioneurins whose main exponent is VEGF. There are situations in which hypoxia is not from an increased activity, but a decrease in available oxygen, as occurs in the altitude exposure.
Our goal is to study the changes underlying microvascular acute adaptation to moderate altitude and the possible effects of physical exercise.
Wistar rats bred to 400 m (P47) and transported to a height of 2800m on a journey of 35 minutes. We used the following cohorts of 7 rats each: a group was housed indoors in standard laboratory conditions, another group had free access to
an exercise wheel. As controls, we used animals born at 400m. After 48 h, animals were sacrificed and after neuropathological examination by conventional histology, capillary density was quantified using computer assisted stereology on thick sections processed using Butyryl Cholinesterase Histochemistry (Argandoña, Brain Res, 1996).
Three cortical areas were quantified, motor, somatosensory and visual cortices.
Rats with free access to exercise wheel showed higher vascular density in response to hypoxia, while the rest showed similar values. Differences were significant in all three areas, being highest in the motor cortex.
The acute adaptation to moderate altitude is an increasingly relevant issue given the increase in displacements at moderate or high altitudes, with serious consequences such as Acute Mountain Sickness, which in its most severe degree leads to
Brain edema. Our results show that exercise can play a protective role through adaptive angiogenesis.

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  • Effects of physical exercise in cerebrovascular mechanisms of adaptation to altitude

    1. 1. !"#$%&()*+*,&%$*)%-&,*$*$)&./*)01/%2* Enrike G. Argandoña  -3%43*-%&),*$14-$*)/4)540*,/*)(/%/.0* Ruddyard Ledezma Harkaitz Bengoetxea )/0/1-$0-"&%2-13456751$/1+)&)8,-139751./1:)"0%)#;)-1365<751*/1:+")*1 365<751"/1%$#8-$13<751!/1$!(%=:-$$!%13<71>1?/@/1+-A)"#)1365<7 Susana Bulnes !"#$%&()%*+",-".(%/,0(12"#$%*",-"3$4*,5+2"674(*5$*",-"89%:%$2".(%/,0(12";<%*=(>4$9 Naiara Ortuzar ?"#$%&()%949"3$9%$4";%5,$"@,>%&4(2";0:(2"@,>%&%4 A"#$%&()%949";4$".(4$:%):,"B4&%("9"CD0E0%)4:42"674(*5$*",-"3$4*,5+2";0:(2"@,>%&%4#$%&(#!%" Irantzu Rico-Barrio F"#$%&()%*+",-"*D"@4)E0"C,0$*(+"#GHIJK#2"674(*5$*",-"L0(,):%$:2"M%,42";74%$ Jose Vicente Lafuente (#)*$+,-&"$%-.,-/+0*1(++2)-3.,-/*+$%*,+"-+/4,+30/"&,+$,(0%-(,+/%+"-#$,(,(+"-+#/"&"/15+"-&%*&"-6+-+"-#$,(,+"-+,-,$61+3,.-37+8%+ +"-#$,(,(+"-+3,.-35+/4,+$,(0%-(,+"(+,9,#/,3+:1+#4-6,(+"-+*%#*+;%<5+:)/+"2+3,.-3+$,."-(+4"645+-6"%6,-"#+0$%#,((+"(+/$"66,$,3+/4$%)64+ Département De Médecine. Université de Fribourg  ./"%-+%2+-,<+#0"**$",(+2$%.+0$,,="(/"-6+&,((,*(7+84,+/$"66,$+2#/%$+%2+-6"%6,-,("(+"(+*%#*+-,)$%-*+410%="+(+$,()*/+%2+"-#$,(,3+#/"&"/15+ Programa de Neurociencias. Universidad Andina Simon Bolivar, Sucre, Bolivia ,3+:1+-6"%6*"%-,)$"-(+<4%(,+."-+,=0%-,-/+"(+>?@A7+84,$,+$,+("/)/"%-(+"-+<4"#4+410%="+"(+-%/+2$%.+-+"-#$,(,3+#/"&"/1+BC$6-3%D5+ Facultad de Medicina, Universidad San Francisco Xavier de Chuquisaca, Sucre, Bolivia :)/++3,#$,(,+"-+&"*:*,+%=16,-5+(+%##)$(+"-+/4,+*/"/)3,+,=0%()$,7 Laboratorio de Neurociencia Experimental (LaNCE). Facultad de Medicina, Universidad del Pais Vasco (UPV/EHU). Leioa. !"#$%& *+"(+/%+(/)31+/4,+#4-6,(+)-3,$*1"-6+."#$%&(#)*$+#)/,+30//"%-+/%+.%3,$/,+*/"/)3,+-3+/4,+0%((":*,+,9,#/(+%2+041("#*+,=,$#"(,7
    2. 2. Efectos del ejercicio fisico en los mecanismos cerebrovasculares de adaptacion a la altura !"#$%&()*+*,&%$*)%-&,*$*$)&./*)01/%2* Enrike G. Argandoña  -3%43*-%&),*$14-$*)/4)540*,/*)(/%/.0* Ruddyard Ledezma Harkaitz Bengoetxea )/0/1-$0-"&%2-13456751$/1+)&)8,-139751./1:)"0%)#;)-1365<751*/1:+")*1 365<751"/1%$#8-$13<751!/1$!(%=:-$$!%13<71>1?/@/1+-A)"#)1365<7 Susana Bulnes !"#$%&()%*+",-".(%/,0(12"#$%*",-"3$4*,5+2"674(*5$*",-"89%:%$2".(%/,0(12";<%*=(>4$9 Naiara Ortuzar ?"#$%&()%949"3$9%$4";%5,$"@,>%&4(2";0:(2"@,>%&%4 A"#$%&()%949";4$".(4$:%):,"B4&%("9"CD0E0%)4:42"674(*5$*",-"3$4*,5+2";0:(2"@,>%&%4#$%&(#!%" Irantzu Rico-Barrio F"#$%&()%*+",-"*D"@4)E0"C,0$*(+"#GHIJK#2"674(*5$*",-"L0(,):%$:2"M%,42";74%$ Jose Vicente Lafuente (#)*$+,-&"$%-.,-/+0*1(++2)-3.,-/*+$%*,+"-+/4,+30/"&,+$,(0%-(,+/%+"-#$,(,(+"-+#/"&"/15+"-&%*&"-6+-+"-#$,(,+"-+,-,$61+3,.-37+8%+ +"-#$,(,(+"-+3,.-35+/4,+$,(0%-(,+"(+,9,#/,3+:1+#4-6,(+"-+*%#*+;%<5+:)/+"2+3,.-3+$,."-(+4"645+-6"%6,-"#+0$%#,((+"(+/$"66,$,3+/4$%)64+ Département De Médecine. Université de Fribourg  ./"%-+%2+-,<+#0"**$",(+2$%.+0$,,="(/"-6+&,((,*(7+84,+/$"66,$+2#/%$+%2+-6"%6,-,("(+"(+*%#*+-,)$%-*+410%="+(+$,()*/+%2+"-#$,(,3+#/"&"/15+ Programa de Neurociencias. Universidad Andina Simon Bolivar, Sucre, Bolivia ,3+:1+-6"%6*"%-,)$"-(+<4%(,+."-+,=0%-,-/+"(+>?@A7+84,$,+$,+("/)/"%-(+"-+<4"#4+410%="+"(+-%/+2$%.+-+"-#$,(,3+#/"&"/1+BC$6-3%D5+ Facultad de Medicina, Universidad San Francisco Xavier de Chuquisaca, Sucre, Bolivia :)/++3,#$,(,+"-+&"*:*,+%=16,-5+(+%##)$(+"-+/4,+*/"/)3,+,=0%()$,7 Laboratorio de Neurociencia Experimental (LaNCE). Facultad de Medicina, Universidad del Pais Vasco (UPV/EHU). Leioa. !"#$%& *+"(+/%+(/)31+/4,+#4-6,(+)-3,$*1"-6+."#$%&(#)*$+#)/,+30//"%-+/%+.%3,$/,+*/"/)3,+-3+/4,+0%((":*,+,9,#/(+%2+041("#*+,=,$#"(,7
    3. 3. EFECTOS DE LA EXPOSICION A ALTURA MODERADA> 2500 m (150M personas)Mal de alturaMal agudo de montaña (HACE, HAPE)Edema vasogénicoSobre 3000 m, 75% de población sintomas leves(cefaleas, Nausea, confusión, anorexia, Fatiga, disnea,alteraciones del sueño, malestar general)
    4. 4. MECANISMOS DE PROTECCIÓN A ALTURA MODERADAGenéticos (HIF). A. Bigham. PLoS 2010Altura moderada protege frente patologiascardiovasculares. (12%/1000m) D. Faeh. Circulation 2009
    5. 5. 4euron Unidad neurogliovascularReviewure 4. Schematic of the Neurovascular UnitEndothelial cells and pericytes are separated by the basement membrane. Pericyte processes sheathe most of the outer side of the basement membrnts of contact, pericytes communicate directly with endothelial cells through the synapse-like peg-socket contacts. Astrocytic endfoot processes uns microvessel wall, which is made up of endothelial cells and pericytes. Resting microglia have a ‘‘ramified’’ shape. In cases of neuronal disorders thimary vascular origin, circulating neurotoxins may cross the BBB to reach their neuronal targets, or proinflammatory signals from the vascular cells or r
    6. 6. 5Angioglioneurinas
    7. 7. Vascularización cortical Red capilar 640 km Un capilar por neurona Barrera hematoencefálica Mecanismos estructurales Mecanismos metabólicos
    8. 8. VEGFVascular Endothelial Growth FactorI. Inductor de: • Proliferación endotelial • Migración endotelial • Inhibición apotosisII. Efectos neurotróficosy neuroprotectoresIII. Permeabilidadvascular
    9. 9. Angiogénesis
    10. 10. Angiogénesis
    11. 11. Angiogénesis
    12. 12. Angiogénesis
    13. 13. Angiogénesis
    14. 14. Angiogénesis
    15. 15. Enriquecimiento ambiental
    16. 16. Enriquecimiento ambiental
    17. 17. Enriquecimiento ambiental
    18. 18. Enriquecimiento ambientalAngiogénesis
    19. 19. Estudio cuantitativo
    20. 20. VEGF levels 6.0 CE Control DR DR-CE 4.5 3.0 1.5 0 14 dpn 21 dpn 28 dpn 35 dpn 42 dpn 49 dpn 56 dpn 63 dpn
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    22. 22. MATERIAL Y METODOSRatas Wistar criadas a 400 m (P47) y transportadas a2800m en 35 minutos. Ratas criadas en condiciones standard Ratas con acceso a rueda de ejercicio Ratas control a 400 m.Se sacrifican a 48 horas.
    23. 23. MATERIAL AND METHODSCuantificación densidad vascular medianteHistoquimia de Butiril ColinesterasaImmunohistoquimia de NeuN, Calbindina,Parvalbumina y Calretinina.
    24. 24. Vascular density
    25. 25. Vascular density
    26. 26. NeuN
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
    28. 28. .%1N" AN":,(*O" %$<%*D" L0$,(54>"5

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