Background: Spinal cord injury (SCI) is heterogeneous in nature and can be complicated by inflammation and scarring in the subarachnoid space (arachnoiditis). The constellation of traumatic injury and arachnoiditis can lead to extensive intraparenchymal cysts or post-traumatic syringomyelia (PTS), due to alterations in fluid flow and pressure dynamics in the subarachnoid space. Hypothesis: Intrathecal injection of a bioengineered hydrogel containing hyaluronan (HA) will improve functional recovery following severe spinal cord injury associated with arachnoiditis. Methods: Acute to subacute pathophysiological events were characterized in non-injured sham rats, rats receiving a clip compression/contusion injury (SCI), rats receiving an intrathecal kaolin injection (Arachnoiditis) and in rats receiving SCI plus kaolin injection (PTS). Next, a HA containing hydrogel (HAMC) or artificial cerbralspinal fluid (aCSF) control was injected into the subarachnoid space 24 hours following PTS injury. To assess treatment efficacy, subacute pathophysiology was assessed as was long-term neurobehavioural and neuroanatomical recovery. Finally, in vitro studies examined the effect of HA on TLR4 activation using lipopolysaccharide in primary rat microglial cultures. Results: PTS animals exhibited a greater parenchymal injury response as compared to the sum of SCI alone or arachnoiditis alone. Injection of HAMC reduced the extent of scarring and inflammation in the subarachnoid space and improved neurobehavioural and neuroanatomical recovery relative to aCSF controls. These improvements were associated with reduced chondroitin sulfate proteoglycan and IL-1α expression and a trend towards and axonal preservation. In vitro studies demonstrated that HA is capable of reducing TLR4 mediated inflammation in microglia. Conclusions: Acute arachnoiditis potentiates the intensity of intraparenchymal inflammatory and scarring events following SCI. When HAMC was injected intrathecally following PTS injury, it mitigated some of the pernicious effects of arachnoiditis. Part of the therapeutic action of HAMC can be attributed to the ability of HA to reduce TLR4 mediated inflammation in microglia, possibly through an extracellular mechanism.

Background: Spinal cord injury (SCI) is heterogeneous in nature and can be complicated by inflammation and scarring in the subarachnoid space (arachnoiditis). The constellation of traumatic injury and arachnoiditis can lead to extensive intraparenchymal cysts or post-traumatic syringomyelia (PTS), due to alterations in fluid flow and pressure dynamics in the subarachnoid space. Hypothesis: Intrathecal injection of a bioengineered hydrogel containing hyaluronan (HA) will improve functional recovery following severe spinal cord injury associated with arachnoiditis. Methods: Acute to subacute pathophysiological events were characterized in non-injured sham rats, rats receiving a clip compression/contusion injury (SCI), rats receiving an intrathecal kaolin injection (Arachnoiditis) and in rats receiving SCI plus kaolin injection (PTS). Next, a HA containing hydrogel (HAMC) or artificial cerbralspinal fluid (aCSF) control was injected into the subarachnoid space 24 hours following PTS injury. To assess treatment efficacy, subacute pathophysiology was assessed as was long-term neurobehavioural and neuroanatomical recovery. Finally, in vitro studies examined the effect of HA on TLR4 activation using lipopolysaccharide in primary rat microglial cultures. Results: PTS animals exhibited a greater parenchymal injury response as compared to the sum of SCI alone or arachnoiditis alone. Injection of HAMC reduced the extent of scarring and inflammation in the subarachnoid space and improved neurobehavioural and neuroanatomical recovery relative to aCSF controls. These improvements were associated with reduced chondroitin sulfate proteoglycan and IL-1α expression and a trend towards and axonal preservation. In vitro studies demonstrated that HA is capable of reducing TLR4 mediated inflammation in microglia. Conclusions: Acute arachnoiditis potentiates the intensity of intraparenchymal inflammatory and scarring events following SCI. When HAMC was injected intrathecally following PTS injury, it mitigated some of the pernicious effects of arachnoiditis. Part of the therapeutic action of HAMC can be attributed to the ability of HA to reduce TLR4 mediated inflammation in microglia, possibly through an extracellular mechanism.

Bibliography: leaves 249-283. / xi, 283 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the hypothesis that cerebrospinal fluid (CSF) is driven from the subarachnoid space into perivascular spaces and the central canal by arterial pulsations and that this is the driving force for the development of non-communicating syringomyelia. Horseradish peroxidase (HRP) is used as a CSF tracer in rats and sheep. A technique for studying the three-dimensional morphology of the human central canal is also developed. / Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery, 1997?

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Submitted by Natalia de Souza Gonçalves (natalia.goncalves@ufpe.br) on 2016-10-10T12:57:26Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) CLAUDIO VIDAL - COLACAO.pdf: 6023190 bytes, checksum: d165c8659f0d2b209cb4a7a228a33bd7 (MD5) / Made available in DSpace on 2016-10-10T12:57:26Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) CLAUDIO VIDAL - COLACAO.pdf: 6023190 bytes, checksum: d165c8659f0d2b209cb4a7a228a33bd7 (MD5) Previous issue date: 2014-06-13 / A alta prevalência de malformação da junção crânio-vertebral (JCV) no Nordeste do Brasil é historicamente associada ao biótipo braquicefálico também comum nessa região. A ectopia tonsilar, marco anatomopatológico da Malformação de Chiari tipo I (MC I), pode ser entendida no contexto de uma desproporção vigente entre o continente (crânio) e seu conteúdo (tecido nervoso) resultante de uma fossa posterior de pequenas dimensões. A forma mais adequada de se tratar a MC I é um dos tópicos mais controversos da neurocirurgia. O presente estudo se propôs a avaliar duas técnicas cirúrgicas comumente empregadas no tratamento da MC I. Métodos: Foram avaliados 32 indivíduos, distribuídos em dois grupos. No Grupo 1, 16 pacientes foram submetidos apenas à descompressão ósteodural da JCV, sem manipulação da membrana aracnoide. No Grupo 2, 16 pacientes foram submetidos à: descompressão ósteodural associada à abertura e dissecção da membrana aracnoide, e redução das tonsilas por termocoagulação e/ou aspiração. A comparação entre os grupos se fundamentou na avaliação de parâmetros clínicos e de Cine Ressonância Magnética do fluxo liquórico, nos períodos que antecederam e sucederam o ato cirúrgico. Resultados: Ambas as técnicas foram equivalentes (p>0,05) em proporcionar melhoria neurológica dos pacientes no período pós-operatório, porém o Grupo 2 cursou com mais complicações pós-operatórias, sendo o risco relativo de 2,45 (I.C.-1,55 a 3,86) para eventos adversos. No que tange à restauração do fluxo liquórico pela JCV no período pósoperatório, a quantidade de LCR que passa pela JCV do Grupo 1 foi maior que no Grupo 2 (p<0,05). Conclusão: A descompressão ósteodural da JCV sem manipulação da aracnoide é a forma mais adequada de tratamento da MC I entre as duas técnicas analisadas / Abnormalities of the craniovertebral junction (CVJ) are highly prevalent in Northeast of Brazil, where it is linked to braquicefalic biotype, also common in this region. The ectopic tonsils are the main anatomopathological feature of the type 1 Chiari Malformation (CM 1) and derived from a small posterior fossa. The best way to treat the CM 1 is one of the most controversial topics in the neurosurgical field. The present study evaluated the two most applied techniques to treat CM 1, by means of clinical and radiological parameters. Methods: A total of 32 patients were evaluated. They were divided in two groups: Group 1 had 16 patients that were submitted to cranio-dural decompression of the CVJ; Group 2 also had 16 patients and in addition to cranio-dural decompression of the CVJ, they also had intra-arachnoid manipulation, including tonsils reductions. These groups were analyzed and compared in terms of neurological exam and cerebrospinal fluid flow imaging by using phase-contrast magnetic resonance technique, in two different times: pre and postoperative periods. Results: Both techniques were equivalents in terms of neurological improvement of the patients (p>0,05), but the Group 2 had more surgical complications, with relative risk for this kind of event, of 2,5. Whatever the cerebrospinal fluid flow at CVJ, the patients of the Group 1 achieved greater amount of flow than the Group 2 (p<0,05) in the postoperative period. Conclusion: The exclusive cranio-dural decompression of the CVJ for treatment of CM 1 had better general results when compared to the addition of intra-arachnoid manipulation to the procedure.

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Modelling of cerebrospinal fluid flow is important for understanding its influence on central nervous system, especially spinal cord. One of the reasons for its study is a disease called syringomyelia that probably develops as a result of severance of neural pathways by bubbles emerging during the propagation of pressure (expan- sion) disturbances through spinal cord and its surroundings. It is characterized by fluid-filled cavities in spinal cord. In this thesis, a model of fluid-filled co-axial elastic tubes is proposed that can help us simulate pressure disturbances propa- gation through spinal cord including its interactions and possible increase as the result of interferences or reflection. We derive quasi-one-dimensional governing equations in the form of nonlinear hyperbolic system of conservational laws and with its numerical solution by two-step Lax-Wendroff method with added artifi- cial viscosity we can quantitatively estimate almost twofold increase of pressure difference. 1