assessing-forelimb-function-after-unilateral-cervical-sci-using-novel

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority ...

noninvasive-in-pen-approach-test-for-laboratory-housed-pigs

Noninvasive, In-pen Approach Test for Laboratory-housed Pigs

Traumatic brain injury (TBI) incidences have increased in both civilian and military populations, and many researchers are adopting a porcine model for ...

The University of Texas at Austin

Lucent Research, LLC

University of Washington

Detection of cell proliferation and cell fate in adult CNS using BrdU double-label immunohistochemistry.

We used in situ hybridization histochemistry to assess expression of dopamine receptors (D1R, D2R and D3R), neurotensin, proenkephalin and glutamate decarboxylase-67 (GAD67) in the prefrontal cortex, striatum, and/or nucleus accumbens in adult rats with neonatal ventral hippocampal (VH) lesions and in control animals after acute and chronic treatment with antipsychotic drugs clozapine and haloperidol. We also acquired these measures in a separate cohort of treatment-naÃ¯ve sham and neonatally VH-lesioned rats used as an animal model of schizophrenia. Our results indicate that the neonatal VH lesion did not alter expression of D1R, D3R, neurotensin or proenkephalin expression in any brain region examined. However, D2R mRNA expression was down-regulated in the striatum, GAD67 mRNA was down-regulated in the prefrontal cortex and prodynorphin mRNA was up-regulated in the striatum of the VH-lesioned rats as compared with sham controls. Antipsychotic drugs did not alter expression of D1R, D2R or D3R receptor mRNAs but elevated neurotensin and proenkephalin expression in both groups of rats; patterns of changes were dependent on the duration of treatment and brain area examined. GAD67 mRNA was up-regulated by chronic antispychotics in the nucleus accumbens and the striatum and by chronic haloperidol in the prefrontal cortex in both sham and lesioned rats. These results indicate that the developmental VH lesion changed the striatal expression of D2R and prodynorphin and robustly compromised prefrontal GAD67 expression but did not modify drug-induced expression of any genes examined in this study.

Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs.

The neonatal ventral hippocampal lesion in the rat has been used as a model of schizophrenia, a human disorder associated with changes in markers of dopamine and gamma-aminobutyric acid (GABA) circuits in various regions of the brain. We investigated whether alterations in mRNA markers related to the activity of midbrain dopaminergic and GABAergic neurons are associated with this model. We used in situ hybridization histochemistry to assess expression of mRNAs for dopamine transporter (DAT), tyrosine hydroxylase (TH) and glutamate decarboxylase-67 (GAD67) in the midbrain of adult rats with neonatal and adult ibotenic acid lesions of the ventral hippocampus. Neonatally lesioned rats showed in adulthood significantly reduced expression of DAT mRNA in the substantia nigra and the ventral tegmental area but no changes in the expression of TH and GAD67 mRNAs in these midbrain regions. Adult lesioned rats showed no changes in the expression of any of these genes. As the neonatal ventral hippocampal lesion reproduces many aspects of schizophrenia and is used as an animal model of this disorder, these results suggest that the reduction in DAT mRNA could result from developmental neuropathology in the ventral hippocampus and may thus represent a molecular substrate of the disease process.

The neonatal ventral hippocampal lesion model of schizophrenia: effects on dopamine and GABA mRNA markers in the rat midbrain.

A fraction derived from presynaptic specializations (presynaptic particle fraction; PPF) can be separated from postsynaptic densities (PSD) by adjusting the pH of Triton X-100 (TX-100) extraction of isolated transsynaptic scaffolds. Solubilization of the PPF corresponds to disruption of the presynaptic specialization. We show that the PPF is insoluble to repeated TX-100 extraction at pH 6.0 but becomes soluble in detergent at pH 8.0. By immunolocalization, we find that the major proteins of the PPF, clathrin and dynamin, are concentrated in the presynaptic compartment. By using multidimensional protein identification technology, we compared the protein compositions of the PPF and the PSD fraction. We identified a total of 341 proteins, 50 of which were uniquely found in the PPF, 231 in the PSD fraction, and 60 in both fractions. Comparison of the two fractions revealed a relatively low proportion of actin and associated proteins and a high proportion of vesicle or intracellular compartment proteins in the PPF. We conclude that the PPF consists of presynaptic proteins not connected to the actin-based synaptic framework; its insolubility in pH 6 and solubility in pH 8 buffered detergent suggests that clathrin might be an anchorage scaffold for many proteins in the PPF.

Proteomic comparison of two fractions derived from the transsynaptic scaffold.

Distinct intracellular pathways are involved in regulated and constitutive protein secretion from neuronal and endocrine cells, yet the peptide signals and molecular mechanisms responsible for targeting and retention of soluble proteins in secretory granules are incompletely understood. By using confocal microscopy and subcellular fractionation, we examined trafficking of the neuronal and endocrine peptide precursor VGF that is stored in large dense core vesicles and undergoes regulated secretion. VGF cofractionated with secretory vesicle membranes but was not detected in detergent-resistant lipid rafts. Deletional analysis using epitope-tagged VGF suggested that the C-terminal 73-amino acid fragment of VGF, containing two predicted alpha-helical loops and four potential prohormone convertase (PC) cleavage sites, was necessary and sufficient with an N-terminal signal peptide-containing domain, for large dense core vesicle sorting and regulated secretion from PC12 and INS-1 cells. Further transfection analysis identified the sorting sequence as a compact C-terminal alpha-helix and embedded 564RRR566 PC cleavage site; mutation of the 564RRR566 PC site in VGF-(1-65): GFP:VGF-(545-617) blocked regulated secretion, whereas disruption of the alpha-helix had no effect. Mutation of the adjacent 567HFHH570 motif, a charged region that might enhance PC cleavage in acidic environments, also blocked regulated release. Finally, inhibition of PC cleavage in PC12 cells using the membrane-permeable synthetic peptide chloromethyl ketone (decanoyl-RVKR-CMK) blocked regulated secretion of VGF. Our studies define a critical RRR-containing C-terminal domain that targets VGF into the regulated pathway in neuronal PC12 and endocrine INS-1 cells, providing additional support for the proposed role that PCs and their cleavage sites play in regulated peptide secretion.

A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway.

CNS synapses are produced rapidly upon pre- and post-synaptic recruitment. However, their composition is known to change during development and we reasoned that this may be reflected in the gross biochemical properties of synapses. We found synaptic structure in adult cortical synaptosomes to be resistant to digestion with trypsin in the presence and absence of calcium ions, contrasting with previous observations. We evaluated the divalent cation dependence and trypsin sensitivities of synapses using synaptosomes from different developmental stages. In contrast to adult synapses, at postnatal day (P) 10 EDTA treatment eliminated approximately 60% of the synapses, and trypsin and EDTA, together, eliminated all junctions. Trypsinization in the presence of calcium eliminated approximately 60% of the junctions at P10. By P35, all synapses were calcium independent, whereas full trypsin resistance was not attained until P49. To compare the calcium dependence and trypsin sensitivity of synapses in another region of the adult brain, we examined synapses from adult (P50) hippocampus. Adult hippocampus maintained a population of synapses that resembled that of P35 cortex. Our results show that synapses are modified over a long time period in the developing cortex. We propose a model in which the addition of synergistic calcium-dependent and -independent adhesive systems stabilize synapses.

Structural stabilization of CNS synapses during postnatal development in rat cortex.

Stem cells and progenitor cells in the central nervous system may have potential for therapeutic use in patients with degenerative diseases or after injury. Neural precursor cells can be grown in culture in the presence of mitogens as aggregates termed neurospheres (NSs), as a source of proliferating progenitor cells. Withdrawal of mitogen and allowing the NSs to adhere to a substrate is the conventional way to study the differentiation potential of the progenitor cells propagated in NSs form. Here we asked if differentiation occurs within NSs cultured in the normal manner, in the presence of mitogen.

Embryonic mescencephalon derived neurospheres contain progenitors as well as differentiated neurons and glia.

We report the ability to direct the differentiation pathway of neural progenitor cells (NPCs) within hydrogels having tunable mechanical properties. By modifying the polymeric sugar hyaluronic acid (HA), a major extracellular matrix component in the fetal mammalian brain, with varying numbers of photocrosslinkable methacrylate groups, hydrogels could be prepared with bulk compressive moduli spanning the threefold range measured for neonatal brain and adult spinal cord. Ventral midbrain-derived NPCs were photoencapsulated into HA hydrogels and remained viable after encapsulation. After three weeks, the majority of NPCs cultured in hydrogels with mechanical properties comparable to those of neonatal brain had differentiated into neurons (ss-III tubulin-positive), many of which had extended long, branched processes, indicative of a relatively mature phenotype. In contrast, NPCs within stiffer hydrogels, with mechanical properties comparable to those of adult brain, had differentiated into mostly astrocytes (glial fibrillary acidic protein (GFAP)-positive). Primary spinal astrocytes cultured in the hydrogel variants for two weeks acquired a spread and elongated morphology only in the stiffest hydrogels evaluated, with mechanical properties similar to adult tissue. Results demonstrate that the mechanical properties of these scaffolds can assert a defining influence on the differentiation of ventral midbrain-derived NPCs, which have strong clinical relevance because of their ability to mature into dopaminergic neurons of the substantia nigra, cells that idiopathically degenerate in individuals suffering from Parkinson's disease.

The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation.

Myelin of the adult central nervous system (CNS) is one of the major sources of inhibitors of axon regeneration following injury. The three known myelin-derived inhibitors (Nogo, MAG, and OMgp) bind with high affinity to the Nogo-66 receptor (NgR) on axons and limit neurite outgrowth. Here we show that RNA aptamers can be generated that bind with high affinity to NgR, compete with myelin-derived inhibitors for binding to NgR, and promote axon elongation of neurons in vitro even in the presence of these inhibitors. Aptamers may have key advantages over protein antagonists, including low immunogenicity and the possibility of ready modification during chemical synthesis for stability, signaling, or immobilization. This first demonstration that aptamers can directly influence neuronal function suggests that aptamers may prove useful for not only healing spinal cord and other neuronal damage, but may be more generally useful as neuromodulators.

Aptamer antagonists of myelin-derived inhibitors promote axon growth.

Acellular grafts are a viable option for use in nerve reconstruction surgeries. Recently, our lab created a novel optimized decellularization procedure that removes immunological material while leaving the majority of the extracellular matrix structure intact. The optimized acellular (OA) graft has been shown to elicit an immune response equal to or less than that elicited by the isograft, the analog of the autograft in the rat model. We investigated the performance of the OA graft to provide functional recovery in a long-term study.

Functional characterization of optimized acellular peripheral nerve graft in a rat sciatic nerve injury model.

&#x810A;&#x9AD3;&#x635F;&#x4F24; (SCI) &#x540E;&#x518D;&#x751F;&#x7684;&#x4E00;&#x4E2A;&#x4E3B;&#x8981;&#x969C;&#x788D;&#x662F;&#x795E;&#x7ECF;&#x8F74;&#x7A81;&#x6E17;&#x900F;&#x548C;&#x75A4;&#x75D5;&#x7EC4;&#x7EC7;&#x901A;&#x8FC7;&#x6210;&#x957F;&#x7684;&#x80FD;&#x529B;&#x3002;SCI &#x540E;, &#x708E;&#x75C7;&#x7EC6;&#x80DE;&#x3001; &#x661F;&#x5F62;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x548C;&#x8111;&#x819C;&#x7EC6;&#x80DE;&#x53D1;&#x6325;&#x53D1;&#x5C55;&#x80F6;&#x8D28;&#x7622;&#x75D5;&#x5F62;&#x6210;&#x4E2D;&#x7684;&#x4F5C;&#x7528;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x672C;&#x673A;&#x9AD8;&#x5206;&#x5B50;&#x91CF; (MW) &#x8D28;&#x9178; (HA) &#x7684;&#x7EC6;&#x80DE;&#x5916;&#x57FA;&#x8D28;&#x4E2D;&#xFF0C;&#x7EC4;&#x4EF6;&#x7684;&#x9000;&#x5316;&#x8868;&#x660E;&#x8BF1;&#x4F7F;&#x6D3B;&#x5316;&#x548C;&#x661F;&#x5F62;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x7684;&#x589E;&#x6B96;&#x3002;&#x4E0D;&#x8FC7;&#xFF0C;&#x5B83;&#x4E0D;&#x662F;&#x77E5;&#x9053;&#x5982;&#x679C;&#x672C;&#x673A;&#x533B;&#x7BA1;&#x5C40;&#x7684;&#x9000;&#x5316;&#x5B9E;&#x9645;&#x4E0A;&#x53EF;&#x589E;&#x5F3A;&#x795E;&#x7ECF;&#x80F6;&#x8D28;&#x7622;&#x75D5;&#x5F62;&#x6210;&#x3002;&#x6211;&#x4EEC;&#x63A8;&#x6D4B;&#x5B58;&#x5728;&#x9AD8; MW &#x516C;&#x9877; (&#x6709;&#x9650;&#x7684;&#x9000;&#x5316;&#x4E0E;&#x533B;&#x7BA1;&#x5C40;&#xFF09; SCI &#x540E;&#x4F1A;&#x51CF;&#x5C11;&#x80F6;&#x8D28;&#x75A4;&#x75D5;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x8868;&#x660E;&#x9AD8; MW &#x516C;&#x9877;&#x51CF;&#x5C11;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#xFF0C;&#x964D;&#x4F4E;&#x65B0;&#x751F;&#x513F;&#x548C;&#x6210;&#x4EBA;&#x661F;&#x5F62;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x7684;&#x786B;&#x9178;&#x8F6F;&#x9AA8;&#x7D20;&#x86CB;&#x767D;&#x591A;&#x7CD6; (CSPG) &#x751F;&#x4EA7;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x521A;&#x5EA6;&#x5339;&#x914D;&#x9AD8;&#x533B;&#x7BA1;&#x5C40;&#x5146;&#x74E6;&#x6C34;&#x51DD;&#x80F6;&#x4EA4;&#x8054;&#x62B5;&#x6297;&#x9000;&#x5316;&#x4E86;&#x690D;&#x5165;&#x810A;&#x9AD3;&#x80CC;&#x534A;&#x6A2A;&#x65AD;&#x635F;&#x4F24;&#x5927;&#x9F20;&#x6A21;&#x578B;&#x3002;&#x6025;&#x6027;&#x7684;&#x65F6;&#x95F4;&#x70B9; &#xFF08;&#x4E00;&#x3001; &#x4E09;&#x81F3;&#x5341;&#x5929;&#x521B;&#x4F24;&#x540E;&#xFF09; &#x5927;&#x5927;&#x51CF;&#x5C11;&#x4E86;&#x514D;&#x75AB;&#x7EC6;&#x80DE; (&#x5DE8;&#x566C;&#x7EC6;&#x80DE;&#x548C;&#x5C0F;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;) &#x7684;&#x7F16;&#x53F7;&#xFF0C;&#x5728;&#x75C5;&#x53D8;&#x90E8;&#x4F4D;&#x4E0E;&#x533B;&#x7BA1;&#x5C40;&#x6C34;&#x51DD;&#x80F6;&#x690D;&#x5165;&#x7269;&#x7684;&#x52A8;&#x7269;&#x4E2D;&#x68C0;&#x6D4B;&#x5230;&#x3002;&#x4E0E;&#x623F;&#x59D4;&#x4F1A;&#x690D;&#x5165;&#x7269;&#x7684;&#x635F;&#x4F24;&#x52A8;&#x7269;&#x8FD8;&#x5C55;&#x51FA;&#x5341;&#x5929;&#x521B;&#x4F24;&#x540E;&#x7684;&#x5927;&#x5927;&#x4F4E;&#x4E8E; CSPG &#x8868;&#x8FBE;&#x3002;&#x7B2C;&#x4E5D;&#x5468;&#x521B;&#x4F24;&#x540E;&#xFF0C;&#x4E0E;&#x533B;&#x7BA1;&#x5C40;&#x6C34;&#x51DD;&#x80F6;&#x690D;&#x5165;&#x52A8;&#x7269;&#x5C55;&#x51FA;&#x661F;&#x5F62;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x53CD;&#x5E94;&#x663E;&#x8457;&#x4E0B;&#x964D;&#xFF0C;&#x4F46;&#x6CA1;&#x6709; CSPG &#x8868;&#x8FBE;&#x663E;&#x8457;&#x6539;&#x53D8;&#x3002;&#x7ED3;&#x5408;&#x8D77;&#x6765;&#xFF0C;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x8868;&#x660E;&#x9AD8; MW &#x516C;&#x9877;&#xFF0C;&#x5F53;&#x7A33;&#x5B9A;&#x9632;&#x6B62;&#x9000;&#x5316;&#xFF0C;&#x7F13;&#x89E3;&#x661F;&#x5F62;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x6D3B;&#x5316;&#x5728;&#x4F53;&#x5916;&#x548C;&#x4F53;&#x5185;&#x3002;&#x533B;&#x7BA1;&#x5C40;&#x690D;&#x5165;&#x7269;&#x7684;&#x5B58;&#x5728;&#x4E5F;&#x663E;&#x8457;&#x8DCC;&#x5E45; CSPG &#x6C89;&#x79EF;&#x5728;&#x5341;&#x5929;&#x540E;&#x8D28;&#x63A7;&#x4E0E;&#x5173;&#x8054;&#x56E0;&#x6B64;&#xFF0C;&#x533B;&#x7BA1;&#x5C40;&#x6839;&#x636E;&#x6C34;&#x51DD;&#x80F6;&#x7CFB;&#x7EDF;&#x5177;&#x6709;&#x5F88;&#x5927;&#x7684;&#x6F5C;&#x529B;&#xFF0C;&#x4E3A;&#x5C3D;&#x91CF;&#x51CF;&#x5C11;&#x610F;&#x5916;&#x75A4;&#x75D5;&#x4F5C;&#x4E3A;&#x672A;&#x6765;&#x4FEE;&#x590D;&#x7B56;&#x7565;&#x7684;&#x4E00;&#x90E8;&#x5206;&#x540E;&#x8D28;&#x63A7;

&#x9AD8;&#x5206;&#x5B50;&#x91CF;&#x900F;&#x660E;&#x8D28;&#x9178;&#x9650;&#x5236;&#x810A;&#x9AD3;&#x635F;&#x4F24;&#x540E;&#x7684;&#x661F;&#x5F62;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x6D3B;&#x5316;&#x53CA;&#x7622;&#x75D5;&#x5F62;&#x6210;&#x3002;

A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.

High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury.

Un obstacle majeur &#xE0; la r&#xE9;g&#xE9;n&#xE9;ration apr&#xE8;s l&#xE9;sion de la moelle &#xE9;pini&#xE8;re (SCI) est la capacit&#xE9; des axones de p&#xE9;n&#xE9;trer et de se d&#xE9;velopper &#xE0; travers le tissu cicatriciel. Apr&#xE8;s SCI, les cellules inflammatoires, les astrocytes et des cellules m&#xE9;ning&#xE9;es jouent tous un r&#xF4;le dans le d&#xE9;veloppement de la cicatrice gliale. En outre, la d&#xE9;gradation de la maternelle &#xE0; haut poids mol&#xE9;culaire (MW) d&#x26;#39;acide hyaluronique (HA), un composant de la matrice extracellulaire, a &#xE9;t&#xE9; montr&#xE9; pour induire l&#x26;#39;activation et la prolif&#xE9;ration des astrocytes. Cependant, on ne sait pas si la d&#xE9;gradation de HA natif am&#xE9;liore effectivement la formation de cicatrices gliales. Nous &#xE9;mettons l&#x26;#39;hypoth&#xE8;se que la pr&#xE9;sence de haute MW HA (HA avec une d&#xE9;gradation limit&#xE9;e) SCI va diminuer apr&#xE8;s gliale cicatrices. Ici, nous d&#xE9;montrons que haute HA MW diminue la prolif&#xE9;ration des cellules et r&#xE9;duit le sulfate de chondro&#xEF;tine prot&#xE9;oglycane (CSPG) la production dans les cultures de astrocytes n&#xE9;onatale et adulte. En outre, la rigidit&#xE9; appari&#xE9;s haute MW hydrogels HA r&#xE9;ticul&#xE9;s &#xE0; r&#xE9;sister &#xE0; la d&#xE9;gradation ont &#xE9;t&#xE9; implant&#xE9;s dans un mod&#xE8;le de rat de blessure h&#xE9;misection spinale dorsale. Le nombre de cellules immunitaires (macrophages et la microglie) d&#xE9;tect&#xE9;s au site de l&#xE9;sion chez les animaux ayant des implants d&#x26;#39;hydrogel HA ont &#xE9;t&#xE9; consid&#xE9;rablement r&#xE9;duits &#xE0; des moments aigus (jours un, trois et dix apr&#xE8;s la l&#xE9;sion). Animaux l&#xE9;s&#xE9;s avec des implants HA &#xE9;galement montr&#xE9; l&#x26;#39;expression GCEP nettement inf&#xE9;rieur &#xE0; dix jours apr&#xE8;s la l&#xE9;sion. A neuf semaines apr&#xE8;s la l&#xE9;sion, les animaux avec des implants d&#x26;#39;hydrogel HA ont pr&#xE9;sent&#xE9; une r&#xE9;ponse significativement diminu&#xE9; astrocytaire, mais il n&#x26;#39;a pas a consid&#xE9;rablement modifi&#xE9; GCEQP expression. Ensemble, ces donn&#xE9;es sugg&#xE8;rent que haute MW HA, quand stabilis&#xE9; contre la d&#xE9;gradation, att&#xE9;nue l&#x26;#39;activation des astrocytes in vitro et in vivo. La pr&#xE9;sence d&#x26;#39;implants HA a &#xE9;galement &#xE9;t&#xE9; associ&#xE9;e &#xE0; une diminution significative de la CSPG d&#xE9;p&#xF4;t &#xE0; dix jours apr&#xE8;s la SCI. Par cons&#xE9;quent, les syst&#xE8;mes d&#x26;#39;hydrogel &#xE0; base d&#x26;#39;HA ont un grand potentiel pour minimiser les cicatrices ind&#xE9;sirables dans le cadre de strat&#xE9;gies de r&#xE9;paration futurs apr&#xE8;s la SCI.

&#xC9;lev&#xE9;e en acide hyaluronique mol&#xE9;culaire poids Limites activation des astrocytes et la formation de cicatrices apr&#xE8;s une blessure m&#xE9;dullaire

Eine gro&szlig;e H&uuml;rde f&uuml;r die Regeneration nach Verletzung des R&uuml;ckenmarks (SCI) ist die F&auml;higkeit der Axone einzudringen und wachsen durch das Narbengewebe. Nach SCI spielen Entz&uuml;ndungszellen, Astrozyten und meningeale Zellen eine Rolle bei der Entwicklung der Gliazellen Narbe. Dar&uuml;ber hinaus hat Verschlechterung der native hohes Molekulargewicht (MW) Hyalurons&auml;ure (HA), eine Komponente der extrazellul&auml;ren Matrix, nachweislich Aktivierung und Vermehrung von Astrozyten induzieren. Jedoch ist es nicht bekannt, wenn die Verschlechterung der native HA eigentlich Gliazellen Narbenbildung erh&ouml;ht. Wir vermuten, dass das Vorhandensein von hohen MW HA (HA mit begrenzten Abbau) nach SCI Gliazellen Narbenbildung verringern werden. Hier zeigen wir, dass hohe MW HA verringert die Zellproliferation und Chondroitinsulfat Proteoglycans (CSPG) Produktion in kultivierten Neugeborenen und Erwachsenen Astrozyten reduziert. Dar&uuml;ber hinaus wurden Steifigkeit passende hohe MW HA Hydrogele vernetzte Abbau widerstehen in einem Rattenmodell der spinalen dorsalen Hemisektion Verletzung implantiert. Die Zahl der Immunzellen (Makrophagen und Mikroglia) entdeckt am Standort L&auml;sion bei Tieren mit HA-Hydrogel-Implantate wurden zu akuten Zeitpunkten (ein, drei oder zehn Tage posttraumatische) deutlich reduziert. Lesioned Tiere mit HA Implantaten zeigte auch deutlich niedriger CSPG Ausdruck an zehn Tagen posttraumatische. Bei neun Wochen posttraumatische Tiere mit HA-Hydrogel-Implantaten ausgestellt eine deutlich verringerte astrozytische Antwort, aber habe nicht wesentlich ver&auml;nderte CSPG Ausdruck. Diese Daten zufolge kombiniert, hohe MW HA, wenn gegen Erniedrigung, stabilisiert Gliazelle Aktivierung in vitro und in-vivo-mildert. Das Vorhandensein von HA-Implantate war auch verbunden mit einem deutlichen R&uuml;ckgang der CSPG Ablagerung zehn Tage nach Sci. Daher enthalten Hydrogel HA-basierten Systemen gro&szlig;es Potenzial zur Minimierung der unerw&uuml;nschten Narben als Teil k&uuml;nftigen Reparatur-Strategien nach Sci.

Hochmolekulare Hyalurons&auml;ure schr&auml;nkt Gliazelle Aktivierung und Narbe Bildung nach Verletzung des R&uuml;ckenmarks.

Un grande ostacolo per rigenerazione dopo la ferita del midollo spinale (SCI) &egrave; la capacit&agrave; degli assoni di penetrare e crescere attraverso il tessuto cicatriziale. Dopo SCI, cellule infiammatorie, astrociti e cellule meningee giocano un ruolo nello sviluppo della cicatrice gliale. Inoltre, la degradazione dell&#39;acido ialuronico nativo ad alto peso molecolare (MW) (HA), un componente della matrice extracellulare, ha dimostrata di indurre l&#39;attivazione e la proliferazione di astrociti. Tuttavia, non &egrave; noto se la degradazione di nativo HA effettivamente migliora la formazione della cicatrice gliale. Si ipotizza che la presenza di alti MW HA (HA con limitato degrado) dopo SCI diminuir&agrave; cicatrici gliali. Qui, ci dimostrano che MW HA ad alta diminuisce la proliferazione cellulare e riduce la produzione di Condroitin solfato proteoglicano (CSPG) negli astrociti colti neonatali e dell&#39;adulti. Inoltre, abbinato a rigidit&agrave; alta MW HA idrogel reticolato di resistere alla degradazione sono stati impiantati in un modello del ratto di lesione spinale dorsale Emisezione. I numeri delle cellule immunitarie (macrofagi e microglia) rilevati presso il sito di lesione negli animali con protesi di idrogel HA si sono sensibilmente ridotti in punti temporali acuta (uno, tre e dieci post-injury giorni). Animali elettivamente con protesi HA esposto anche espressione CSPG significativamente inferiore al post-injury di dieci giorni. A post-injury di nove settimane, animali con protesi di idrogel HA esibito una risposta astrocitario significativamente diminuita, ma non hanno significativamente alterata espressione CSPG. Combinati, questi dati suggeriscono che MW HA ad alta, quando stabilizzato contro la degradazione, mitiga attivazione Astrocita in vitro e in vivo. La presenza di impianti HA era anche associata con una diminuzione significativa nella deposizione CSPG a dieci giorni dopo SCI. Pertanto, idrogel HA basato su sistemi contenere grandi potenzialit&agrave; per ridurre cicatrici indesiderate come parte delle strategie di riparazione futura dopo SCI.

Acido ialuronico ad alto peso molecolare limita la formazione di attivazione e cicatrice Astrocita dopo la ferita del midollo spinale.

&#x810A;&#x9AC4;&#x640D;&#x50B7;&#x5F8C;&#x306E;&#x518D;&#x751F;&#x306E;&#x305F;&#x3081;&#x306E;&#x4E3B;&#x8981;&#x306A;&#x30CF;&#x30FC;&#x30C9;&#x30EB;&#xFF08;SCI&#xFF09;&#x306F;&#x3001;&#x7622;&#x75D5;&#x7D44;&#x7E54;&#x3092;&#x8CAB;&#x901A;&#x3057;&#x3066;&#x6210;&#x9577;&#x3059;&#x308B;&#x8EF8;&#x7D22;&#x306E;&#x80FD;&#x529B;&#x3067;&#x3042;&#x308B;&#x3002; SCI&#x306E;&#x5F8C;&#x3001;&#x708E;&#x75C7;&#x6027;&#x7D30;&#x80DE;&#x3001;&#x30A2;&#x30B9;&#x30C8;&#x30ED;&#x30B5;&#x30A4;&#x30C8;&#x3068;&#x9AC4;&#x819C;&#x306E;&#x7D30;&#x80DE;&#x306F;&#x3001;&#x3059;&#x3079;&#x3066;&#x306E;&#x30B0;&#x30EA;&#x30A2;&#x7622;&#x75D5;&#x3092;&#x958B;&#x767A;&#x3059;&#x308B;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x52A0;&#x3048;&#x3066;&#x3001;&#x30CD;&#x30A4;&#x30C6;&#x30A3;&#x30D6;&#x306E;&#x9AD8;&#x3044;&#x5206;&#x5B50;&#x91CF;&#x306E;&#x4F4E;&#x4E0B;&#xFF08;MW&#xFF09;&#x30D2;&#x30A2;&#x30EB;&#x30ED;&#x30F3;&#x9178;&#xFF08;HA&#xFF09;&#x3001;&#x7D30;&#x80DE;&#x5916;&#x30DE;&#x30C8;&#x30EA;&#x30C3;&#x30AF;&#x30B9;&#x306E;&#x6210;&#x5206;&#x306F;&#x3001;&#x30A2;&#x30B9;&#x30C8;&#x30ED;&#x30B5;&#x30A4;&#x30C8;&#x306E;&#x6D3B;&#x6027;&#x5316;&#x3068;&#x5897;&#x6B96;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x793A;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x3002;&#x30CD;&#x30A4;&#x30C6;&#x30A3;&#x30D6;HA&#x306E;&#x5206;&#x89E3;&#x306F;&#x3001;&#x5B9F;&#x969B;&#x306B;&#x30B0;&#x30EA;&#x30A2;&#x7622;&#x75D5;&#x5F62;&#x6210;&#x3092;&#x5F37;&#x5316;&#x3059;&#x308B;&#x5834;&#x5408;&#x306F;&#x3001;&#x305D;&#x308C;&#x304C;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x306A;&#x3044;&#x3002;&#x6211;&#x3005;&#x306F;&#x3001;SCI&#x5F8C;&#x306E;&#x9AD8;MW HA&#xFF08;&#x9650;&#x3089;&#x308C;&#x305F;&#x52A3;&#x5316;HA&#xFF09;&#x306E;&#x5B58;&#x5728;&#x304C;&#x7622;&#x75D5;&#x5316;&#x30B0;&#x30EA;&#x30A2;&#x7D30;&#x80DE;&#x6E1B;&#x5C11;&#x3059;&#x308B;&#x3068;&#x4EEE;&#x5B9A;&#x3057;&#x305F;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x9AD8;&#x3044;MW&#x306E;HA&#x306F;&#x7D30;&#x80DE;&#x5897;&#x6B96;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x3001;&#x57F9;&#x990A;&#x3055;&#x308C;&#x305F;&#x65B0;&#x751F;&#x5150;&#x3068;&#x6210;&#x4EBA;&#x30A2;&#x30B9;&#x30C8;&#x30ED;&#x30B5;&#x30A4;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x30B3;&#x30F3;&#x30C9;&#x30ED;&#x30A4;&#x30C1;&#x30F3;&#x786B;&#x9178;&#x30D7;&#x30ED;&#x30C6;&#x30AA;&#x30B0;&#x30EA;&#x30AB;&#x30F3;&#xFF08;CSPG&#xFF09;&#x306E;&#x751F;&#x7523;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x525B;&#x6027;&#x3092;&#x30DE;&#x30C3;&#x30C1;&#x3055;&#x305B;&#x305F;&#x9AD8;MW&#x306E;HA&#x306F;&#x3001;&#x5206;&#x89E3;&#x306B;&#x62B5;&#x6297;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x67B6;&#x6A4B;&#x30D2;&#x30C9;&#x30ED;&#x30B2;&#x30EB;&#x810A;&#x9AC4;&#x7247;&#x5074;&#x5207;&#x65AD;&#x640D;&#x50B7;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x30E2;&#x30C7;&#x30EB;&#x306B;&#x79FB;&#x690D;&#x3057;&#x305F;&#x3002; HA&#x30CF;&#x30A4;&#x30C9;&#x30ED;&#x30B2;&#x30EB;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x3092;&#x52D5;&#x7269;&#x306E;&#x75C5;&#x5909;&#x90E8;&#x4F4D;&#x3067;&#x691C;&#x51FA;&#x3055;&#x308C;&#x305F;&#x514D;&#x75AB;&#x7D30;&#x80DE;&#xFF08;&#x30DE;&#x30AF;&#x30ED;&#x30D5;&#x30A1;&#x30FC;&#x30B8;&#x3068;&#x30DF;&#x30AF;&#x30ED;&#x30B0;&#x30EA;&#x30A2;&#xFF09;&#x306E;&#x6570;&#x304C;&#x5927;&#x5E45;&#x306B;&#x6025;&#x6027;&#x306E;&#x6642;&#x70B9;&#xFF08;1&#x3001;3&#x301C;10&#x65E5;&#x5F8C;&#x306B;&#x50B7;&#x5BB3;&#xFF09;&#x3067;&#x6E1B;&#x5C11;&#x3057;&#x305F;&#x3002; HA&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x3068;&#x75C5;&#x5909;&#x306E;&#x52D5;&#x7269;&#x306F;&#x307E;&#x305F;&#x3001;10&#x65E5;&#x5F8C;&#x306B;&#x50B7;&#x5BB3;&#x3067;&#x6709;&#x610F;&#x306B;&#x4F4E;&#x304B;&#x3063;CSPG&#x767A;&#x73FE;&#x3092;&#x793A;&#x3057;&#x305F;&#x3002; 9&#x9031;&#x9593;&#x5F8C;&#x306E;&#x3051;&#x304C;&#x3067;&#x3001;HA&#x30CF;&#x30A4;&#x30C9;&#x30ED;&#x30B2;&#x30EB;&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x306E;&#x52D5;&#x7269;&#x304C;&#x6709;&#x610F;&#x306B;&#x6E1B;&#x5C11;&#x3057;&#x305F;&#x30A2;&#x30B9;&#x30C8;&#x30ED;&#x30B5;&#x30A4;&#x30C8;&#x306E;&#x53CD;&#x5FDC;&#x3092;&#x793A;&#x3057;&#x305F;&#x304C;&#x3001;&#x6709;&#x610F;&#x306B;&#x767A;&#x73FE;&#x304C;CSPG&#x5909;&#x66F4;&#x3057;&#x3066;&#x3044;&#x307E;&#x305B;&#x3093;&#x3067;&#x3057;&#x305F;&#x3002;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x308B;&#x3053;&#x3068;&#x3067;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x3001;&#x52A3;&#x5316;&#x306B;&#x5BFE;&#x3057;&#x3066;&#x5B89;&#x5B9A;&#x5316;&#x3001;&#x9AD8;MW HA&#x306F;&#x3001;in vitro&#x304A;&#x3088;&#x3073;in vivo&#x3067;&#x30A2;&#x30B9;&#x30C8;&#x30ED;&#x30B5;&#x30A4;&#x30C8;&#x306E;&#x6D3B;&#x6027;&#x5316;&#x3092;&#x8EFD;&#x6E1B;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x304A;&#x52E7;&#x3081;&#x3057;&#x307E;&#x3059;&#x3002; HA&#x30A4;&#x30F3;&#x30D7;&#x30E9;&#x30F3;&#x30C8;&#x306E;&#x5B58;&#x5728;&#x306F;&#x307E;&#x305F;&#x3001;SCI&#x5F8C;10&#x65E5;&#x76EE;&#x306B;&#x5806;&#x7A4D;&#x3092;CSPG&#x306E;&#x6709;&#x610F;&#x306A;&#x6E1B;&#x5C11;&#x3068;&#x95A2;&#x9023;&#x3057;&#x3066;&#x3044;&#x305F;&#x3002;&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x3001;HA&#x30D9;&#x30FC;&#x30B9;&#x306E;&#x30CF;&#x30A4;&#x30C9;&#x30ED;&#x30B2;&#x30EB;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x306F;&#x3001;&#x671B;&#x307E;&#x3057;&#x304F;&#x306A;&#x3044;SCI&#x5F8C;&#x306E;&#x5C06;&#x6765;&#x306E;&#x4FEE;&#x5FA9;&#x6226;&#x7565;&#x306E;&#x4E00;&#x74B0;&#x3068;&#x3057;&#x3066;&#x7622;&#x75D5;&#x3092;&#x6700;&#x5C0F;&#x9650;&#x306B;&#x6291;&#x3048;&#x308B;&#x305F;&#x3081;&#x306E;&#x5927;&#x304D;&#x306A;&#x53EF;&#x80FD;&#x6027;&#x3092;&#x79D8;&#x3081;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x9AD8;&#x3044;&#x5206;&#x5B50;&#x91CF;&#x306E;&#x30D2;&#x30A2;&#x30EB;&#x30ED;&#x30F3;&#x9178;&#x306F;&#x3001;&#x810A;&#x9AC4;&#x640D;&#x50B7;&#x5F8C;&#x306E;&#x661F;&#x72B6;&#x81A0;&#x7D30;&#x80DE;&#x6D3B;&#x6027;&#x5316;&#x3068;&#x7622;&#x75D5;&#x5F62;&#x6210;&#x3092;&#x5236;&#x9650;&#x3057;&#x307E;&#x3059;&#x3002;

&#xC7AC;&#xC0DD;&#xC131; &#xD6C4; &#xCC99;&#xC218; &#xC0C1;&#xD574; (SCI)&#xC5D0; &#xCE68;&#xD22C; &#xD558; &#xC5EC; &#xBC18; &#xD754; &#xC870;&#xC9C1;&#xC744; &#xD1B5;&#xD574; &#xC131;&#xC7A5; &#xCD95; &#xC0AD;&#xC758; &#xB2A5;&#xB825;&#xC5D0; &#xB300; &#xD55C; &#xC8FC;&#xC694; &#xC7A5;&#xC560;&#xBB3C;. SCI, &#xD6C4; &#xC5FC;&#xC99D; &#xC138;&#xD3EC;, &#xC774;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; meningeal &#xC140; &#xAD50; &#xD749;&#xD130; &#xAC1C;&#xBC1C;&#xC5D0; &#xC5ED;&#xD560;&#xC744; &#xD560;. &#xB610;&#xD55C;, &#xB124;&#xC774;&#xD2F0;&#xBE0C; &#xACE0; &#xBD84;&#xC790;&#xB7C9; (MW) &#xD788; &#xC54C;&#xB8E8; &#xB860; &#xC0B0; (HA), &#xC138;&#xD3EC; &#xC678; &#xB9E4;&#xD2B8;&#xB9AD;&#xC2A4;&#xC758; &#xAD6C;&#xC131; &#xC694;&#xC18C;&#xC758; &#xC800;&#xD558; &#xC774;&#xB2E4;&#xC758; &#xD655;&#xC0B0; &#xBC0F; &#xD65C;&#xC131;&#xD654; &#xC720;&#xB3C4;&#xB97C; &#xBCF4;&#xC5EC;&#xC654;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xB124;&#xC774;&#xD2F0;&#xBE0C; &#xD558; &#xC800;&#xD558; &#xC2E4;&#xC81C;&#xB85C; &#xAD50; &#xD749;&#xD130; &#xD615;&#xC131;&#xC744; &#xAC15;&#xD654; &#xD558;&#xB294; &#xACBD;&#xC6B0; &#xC54C;&#xB824;&#xC838; &#xC788;&#xC9C0; &#xC54A;&#xB2E4;. &#xC6B0;&#xB9AC; &#xAC00;&#xC124;&#xC758; &#xB192;&#xC740; MW &#xD5E5;&#xD0C0;&#xB974; (HA &#xC81C;&#xD55C; &#xC800;&#xD558;) SCI &#xD6C4; &#xC874;&#xC7AC; &#xAD50; &#xD749;&#xD130; &#xAC10;&#xC18C; &#xB429;&#xB2C8;&#xB2E4;. &#xC5EC;&#xAE30;&#xC5D0;, &#xC6B0;&#xB9AC;&#xB294; &#xB192;&#xC740; MW &#xD558; &#xC138;&#xD3EC; &#xC99D;&#xC2DD;&#xC744; &#xAC10;&#xC18C; &#xBC0F; &#xAD50;&#xC591; &#xC2E0;&#xC0DD;&#xC544; &#xBC0F; &#xC131;&#xC778; &#xC774;&#xB2E4;&#xC5D0;&#xC11C; &#xCF58; proteoglycan (CSPG) &#xC0DD;&#xC0B0;&#xC744; &#xAC10;&#xC18C;&#xB97C; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, &#xC77C;&#xCE58; &#xD558;&#xB294; &#xAC15;&#xC131; &#xB192;&#xC740; MW &#xD558; hydrogels crosslinked &#xC800;&#xD558;&#xC5D0; &#xC800;&#xD56D; &#xD558;&#xB294; &#xCC99;&#xCD94; &#xB4F1; hemisection &#xC0C1;&#xD574;&#xC758; &#xC950; &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xC774;&#xC2DD; &#xD588;&#xB2E4;. HA hydrogel &#xBCF4; &#xD615; &#xBB3C;&#xACFC; &#xB3D9;&#xBB3C;&#xC5D0;&#xC11C; &#xBCD1; &#xBCC0; &#xC0AC;&#xC774;&#xD2B8;&#xC5D0;&#xC11C; &#xBA74;&#xC5ED; &#xC138;&#xD3EC; (&#xB300; &#xC2DD; &#xC138;&#xD3EC; &#xBC0F; microglia)&#xC758; &#xC22B;&#xC790; &#xAE09;&#xC131; &#xC2DC;&#xAC04; &#xD3EC;&#xC778;&#xD2B8; (1, 3&#xACFC; 10 &#xC77C; &#xD3EC;&#xC2A4;&#xD2B8;)&#xC5D0;&#xC11C; &#xD06C;&#xAC8C; &#xAC10;&#xC18C; &#xD588;&#xB2E4;. HA &#xC784; &#xD50C; &#xB780; &#xD2B8;&#xC640; lesioned &#xB3D9;&#xBB3C;&#xB3C4; &#xC0C1;&#xB2F9;&#xD788; &#xB0AE;&#xC740; CSPG &#xC2DD;&#xC744; 10 &#xC77C; &#xD3EC;&#xC2A4;&#xD2B8;&#xC5D0; &#xC804;&#xC2DC;. 9 &#xC8FC; &#xD3EC;&#xC2A4;&#xD2B8;&#xC5D0;&#xC11C; HA hydrogel &#xBCF4; &#xD615; &#xBB3C;&#xACFC; &#xB3D9;&#xBB3C; &#xB300;&#xD3ED; &#xAC10;&#xC18C; astrocytic &#xC751;&#xB2F5;&#xC744; &#xC804;&#xC2DC; &#xD558;&#xC9C0;&#xB9CC; &#xD06C;&#xAC8C; &#xBCC0;&#xACBD; &#xB41C; CSPG &#xC2DD; &#xC5C6;. &#xACB0;&#xD569;, &#xC774;&#xB7EC;&#xD55C; &#xB370;&#xC774;&#xD130;&#xB294; &#xB192;&#xC740; MW &#xD558;, &#xC800;&#xD558;&#xC5D0; &#xB300; &#xD55C; &#xC548;&#xC815; &#xB54C; &#xC644;&#xD654; &#xC0AC;&#xC774;&#xD1A0; &#xD65C;&#xC131;&#xD654; &#xC0DD;&#xCCB4; &#xC678; &#xBC0F; &#xC0DD;&#xCCB4; &#xC870;&#xAC74; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;. HA &#xC784; &#xD50C; &#xB780; &#xD2B8;&#xC758; &#xC874;&#xC7AC;&#xB294; &#xB610;&#xD55C; &#xACFC;&#xD559; &#xD6C4; 10 &#xC77C; &#xB0B4;&#xC5D0; CSPG &#xC99D; &#xCC29;&#xC5D0; &#xD070; &#xAC10;&#xC18C;&#xC640; &#xAD00;&#xB828; Hydrogel &#xD558; &#xAE30;&#xBC18; &#xC2DC;&#xC2A4;&#xD15C; &#xACFC;&#xD559; &#xD6C4; &#xD5A5;&#xD6C4; &#xBCF5;&#xAD6C; &#xC804;&#xB7B5;&#xC758; &#xC77C;&#xD658;&#xC73C;&#xB85C; &#xC6D0;&#xCE58; &#xC54A;&#xB294; &#xD749;&#xD130;&#xB97C; &#xCD5C;&#xC18C;&#xD654; &#xD558;&#xAE30; &#xC704;&#xD55C; &#xD070; &#xC7A0;&#xC7AC;&#xB825;&#xC744; &#xBCF4;&#xC720; &#xD558;&#xB294; &#xB530;&#xB77C;&#xC11C;

&#xACE0; &#xBD84;&#xC790;&#xB7C9; &#xD788; &#xC54C;&#xB8E8; &#xB860; &#xC0B0; &#xCC99;&#xC218; &#xC190;&#xC0C1; &#xD6C4; &#xC0AC;&#xC774;&#xD1A0; &#xD65C;&#xC131;&#xD654; &#xBC0F; &#xD749;&#xD130; &#xD615;&#xC131;&#xC744; &#xC81C;&#xD55C;&#xD569;&#xB2C8;&#xB2E4;.

Un obst&#xE1;culo importante para la regeneraci&#xF3;n despu&#xE9;s de la lesi&#xF3;n de la m&#xE9;dula espinal (LME) es la capacidad de los axones para penetrar y crecer a trav&#xE9;s del tejido de la cicatriz. Despu&#xE9;s de la lesi&#xF3;n, las c&#xE9;lulas inflamatorias, astrocitos y c&#xE9;lulas men&#xED;ngeas tienen un papel en el desarrollo de la cicatriz glial. Adem&#xE1;s, la degradaci&#xF3;n de nativo de alto peso molecular (PM) de &#xE1;cido hialur&#xF3;nico (HA), un componente de la matriz extracelular, se ha demostrado que induce la activaci&#xF3;n y proliferaci&#xF3;n de astrocitos. Sin embargo, no se sabe si la degradaci&#xF3;n de HA nativa realmente aumenta la formaci&#xF3;n de cicatriz glial. Nuestra hip&#xF3;tesis es que la presencia de alta HA MW (HA con la degradaci&#xF3;n del limitado) despu&#xE9;s de la lesi&#xF3;n se reducir&#xE1; glial cicatrices. Este sentido, demuestran que la alta HA MW disminuye la proliferaci&#xF3;n celular y reduce el sulfato de condroitina proteoglicanos (CSPG) la producci&#xF3;n en cultivos de astrocitos neonatales y de adultos. Adem&#xE1;s, la rigidez de concordancia alta MW hidrogeles HA reticulados para resistir la degradaci&#xF3;n fueron implantados en un modelo de rata de la lesi&#xF3;n en la columna hemisecci&#xF3;n dorsal. El n&#xFA;mero de c&#xE9;lulas inmunol&#xF3;gicas (macr&#xF3;fagos y microglia) detectados en el sitio de la lesi&#xF3;n en animales con implantes de hidrogel HA se redujeron significativamente en los puntos m&#xE1;s agudos (los d&#xED;as uno, tres y diez despu&#xE9;s de la lesi&#xF3;n). Animales lesionados con los implantes de HA tambi&#xE9;n mostraron una expresi&#xF3;n significativamente menor CSPG menos diez d&#xED;as despu&#xE9;s de la lesi&#xF3;n. A las nueve semanas despu&#xE9;s de la lesi&#xF3;n, los animales con implantes de hidrogel HA mostraron una respuesta significativa disminuci&#xF3;n de los astrocitos, pero no han alterado significativamente CSPG expresi&#xF3;n. En conjunto, estos datos sugieren que la alta HA MW, cuando estabilizada contra la degradaci&#xF3;n, mitiga la activaci&#xF3;n de astrocitos in vitro e in vivo. La presencia de los implantes de HA tambi&#xE9;n se asoci&#xF3; con una disminuci&#xF3;n significativa en CSPG dep&#xF3;sito, diez d&#xED;as despu&#xE9;s de la lesi&#xF3;n. Por lo tanto, HA sistemas basados &#x200B;&#x200B;en hidrogeles tienen un gran potencial para reducir al m&#xED;nimo las cicatrices no deseadas, como parte de estrategias de reparaci&#xF3;n en el futuro despu&#xE9;s de la lesi&#xF3;n.

Molecular del &#xE1;cido hialur&#xF3;nico de alto peso L&#xED;mites de la activaci&#xF3;n de astrocitos y formaci&#xF3;n de cicatrices despu&#xE9;s de una lesi&#xF3;n de la m&#xE9;dula espinal

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forelimb placing tests. In addition, a forelimb step-alternation test was developed to assess functional recovery at 12 weeks post-injury. All tests detected cSCI-induced deficits relative to laminectomy. Interestingly, the severity of deficits in the forelimb step-alternation test was associated with more extensive spinal damage, greater impairment, and less recovery in the FLS and other tests. For the pasta-handling test we found that rats with a milder cervical injury (alternators) were more likely to use both forepaws together compared to rats with a more severe injury (non-alternators). In addition, using the PIT, we detected enhanced function of the good limb, suggesting that neural plasticity on the unaffected side of the spinal cord may have occurred to compensate for deficits in the impaired forelimb. These outcome measures should be useful for investigating neural events associated with cSCI, and for developing novel treatment strategies.

Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery.

Natural biomaterials are well positioned to play a significant role in the development of the next generation of biomaterials for nervous system repair. These materials are derived from naturally occurring substances and are highly diverse and versatile. They are generally biocompatible and are well tolerated in vivo, and therefore have a high potential to be successful as part of clinical repair strategies in the nervous system. Here we review recent reports on acellular tissue grafts, collagen, hyaluronan, fibrin, and agarose in their use to repair the nervous system. In addition, newly developed advanced fabrication techniques to further develop the next generation natural biomaterials-based therapeutic devices are discussed.

Advances in natural biomaterials for nerve tissue repair.

Clinical evidence suggests that nano- and microtopography incorporated into scaffolds does not merely improve peripheral nerve regeneration, but is in fact a prerequisite for meaningful restoration of nerve function. Although the biological mechanisms involved are not fully understood, grafts incorporating physical guides that mimic microscopic nerve tissue features (e.g., basal laminae) appear to provide a significant advantage over grafts that rely on purely chemical or macroscopic similarities to nerve tissue. Investigators consistently demonstrate the fundamental importance of nano- and micro-scale physical features for appropriate cell response in a wide range of biological scenarios. Additionally, recent in vivo research demonstrates that nerve regeneration scaffolds with cell-scale physical features are more effective than those that rely only on chemical or macro-scale features. Physical guidance at the cell-scale is especially important for long (>20 mm) nerve defects, for which the only reliable treatment is the autologous nerve graft. The lack of other available options exposes a clear need for the application of nano- and microfabrication techniques that will allow the next generation of engineered nerve guides to more closely mimic native tissue at those scales. This review examines current research to determine what elements of cell-scale topography in experimental scaffolds are most effective at stimulating functional recovery, and then presents an overview of fabrication techniques that could potentially improve future treatment paradigms. Relative advantages and disadvantages of these techniques are discussed, with respect to both clinical adaptation and likely effectiveness. Our intent is to more clearly delineate the remaining obstacles in the development of a next generation nerve guide, particularly for long defects, and offer new perspectives on steering current technologies towards clinically viable solutions.

ArticleTotal : 2	Year
Publication title Cited by 9	2013
Publication title Cited by 3	2019

Article	Year
Detection of cell proliferation and cell fate in adult CNS using BrdU double-label immunohistochemistry. Methods in molecular medicine\| PubMed ID: 12506720	2003
Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs. The European journal of neuroscience\| PubMed ID: 12887421	2003
The neonatal ventral hippocampal lesion model of schizophrenia: effects on dopamine and GABA mRNA markers in the rat midbrain. The European journal of neuroscience\| PubMed ID: 14656305	2003
Proteomic comparison of two fractions derived from the transsynaptic scaffold. Journal of neuroscience research\| PubMed ID: 16047384	2005
A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway. The Journal of biological chemistry\| PubMed ID: 16221685	2005
Structural stabilization of CNS synapses during postnatal development in rat cortex. Journal of neurochemistry\| PubMed ID: 16805840	2006
Embryonic mescencephalon derived neurospheres contain progenitors as well as differentiated neurons and glia. Restorative neurology and neuroscience\| PubMed ID: 20042785	2009
The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation. Biomaterials\| PubMed ID: 20171731	2010
Aptamer antagonists of myelin-derived inhibitors promote axon growth. PloS one\| PubMed ID: 20300533	2010
Functional characterization of optimized acellular peripheral nerve graft in a rat sciatic nerve injury model. Neurological research\| PubMed ID: 21708069	2011
High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury. Journal of neural engineering\| PubMed ID: 21753237	2011
Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery. Journal of neurotrauma\| PubMed ID: 22022897	2012
Advances in natural biomaterials for nerve tissue repair. Neuroscience letters\| PubMed ID: 22366403	2012
The fundamental role of subcellular topography in peripheral nerve repair therapies. Biomaterials\| PubMed ID: 22425024	2012

Zin Z. Khaing

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