INTRODUCTION: Increased production and disorders in the circulation or absorption of cerebrospinal fluid (CSF) leads to increased intracranial pressure and causes a condition called hydrocephalus. The most common treatment for this disorder is the implantation of a ventricle-peritoneal shunt, which consists of the insertion of a ventricular catheter in the cerebral ventricle, a neurological valve for drainage control and a peritoneal catheter that leads the CSF to the abdominal region. The International Organization for Standardization (ISO) 7197 introduced requirements for the design and production of the shunts and neurological valve, including in vitro hydrodynamic tests, which are indispensable for evaluating the performance of the CSF drainage systems. METHODS: A testing rig built in accordance with ISO 7197 was evaluated for the uncertainty of flow and opening and closing pressure measurements, the pressure-flow relationship and reflux neurological valve resistance. The infusion pump and pressure measurement system were evaluated for calibration, hysteresis behavior and stability to determine the experimental uncertainties from hydrodynamic testing of two commercial products. RESULTS: The equipment showed uncertainties of less than 1% in the infusion pump, less than 4% in the pressure sensor and adequate performance for the hydrodynamic tests. CONCLUSION: The hydrodynamic test rig allowed the opening and closing pressures and the resistance to reflux to be obtained, and it also allowed the determination of the pressure and flow rate characteristics of two neurological commercial valves with experimental uncertainties that do not impact the results and the evaluation of in vitro performance of a shunt.

O fator estimulador de colônias granulocitárias (G-CSF) é uma glicoproteína descrita há mais de vinte anos, e é largamente utilizada para tratamento de estados neutropênicos e no transplante de medula óssea. O G-CSF estimula células-tronco hematopoéticas e regula crucialmente a sobrevivência de neutrófilos maduros, pós-mitóticos, através da inibição da apoptose. Além do efeito sistêmico, mais recentemente tem-se demonstrado uma surpreendente atividade do G-CSF no sistema nervoso central. A administração de G-CSF mobiliza células-tronco e progenitoras da medula óssea para o sangue periférico, que, por sua vez, atravessa a barreira hemato-encefálica (BHE) e se dirige à área acometida do cérebro. A atividade do G-CSF no sistema nervoso central tem sido caracterizada como multimodal, pois, além do efeito mobilizador de células da medula óssea, demonstrou uma ação direta neuroprotetora através de diferentes mecanismos, tais como a atividade antiapoptótica em neurônios, regeneração da vascularização, efeito anti-inflamatório e estimulação da neurogênese endógena. Este relato sumariza a ação do G-CSF no sistema nervoso central e aborda seu potencial para o emprego no acidente vascular cerebral.

The granulocyte colony-stimulating-factor (G-CSF) is a glycoproteina which has been described for decades, and it is commonly utilized in the treatment of neutropenic states and bone marrow transplants. G-CSF stimulates hematopoietic stem-cels e crucially regulates the survival of mature neutrophils through a mechanism of apoptosis inhibition. Beyond its systemic effect, recently it has been shown its surprising activity in the central nervous system (CNS). G-CSF administration mobilizes bone marrow stem cells para systemic blood, and those cells cross the blood-brain-barrier e target brain's damaged area. G-CSF's activity in the CNS has been defined as multimodal, because additionally it has been demonstrated a direct neuroprotective action through different mechanisms such as antiapoptotic activity, angiogenesis, anti-inflamatory effect, and stimulation of endogenous neurogenesis. This paper sumarizes G-CSF action in the CNS and approaches its potential para use in stroke.

Nesta revisão são abordadas as doenças em que existem dados e perspectivas do uso de transplante de células-tronco hematopoéticas em suas diversas modalidades. São apresentados também os aspectos referentes aos regimes de condicionamento empregados, e sua relação com toxicidade e taxa de mortalidade ligadas ao transplante. São apresentadas as doenças autoimunes e particularizados dados específicos do lúpus eritematoso sistêmico, esclerose sistêmica e esclerose múltipla e diabetes mellitus tipo 1. A base do procedimento nas doenças autoimunes é a reprogramação imunológica. Aparentemente o procedimento tem sua indicação nas doenças em que os tratamentos convencionais de imunossupressão tenham falhado, e o dano orgânico não tenha sido definitivo, mas tenha chance de ocorrer caso não seja realizado o transplante. A modalidade aparentemente indicada no momento deve ser o transplante de células-tronco autogênico com regimes de condicionamento não mieloablativo para se obter sobrevivência estimada em mais de 50% em todas as doenças, com baixa toxicidade e com mortalidade nula ligada ao transplante. São apresentados também os resultados nos tumores sólidos, que são discutíveis, e particularidades no câncer de mama. A aparente indicação para os tumores sólidos é transplante de células-tronco alogênico e se baseia no tratamento intensivo com doses mieloablativas com a finalidade de se induzir o efeito enxerto contra o tumor. Os regimes não mieloablativos são preconizados com a finalidade de redução da toxicidade e indução de imunossupressão, sendo os dados insuficientes e discutíveis, o que obriga a introdução de novas estratégias terapêuticas baseadas na terapia imune e celular.

In this report we discuss data and perspectives of hematopoietic stem cell transplantation in non-hematologic diseases. Aspects related to the conditioning regimen and its relationship with toxicity and mortality are also presented. Specific autoimmune diseases are discussed, in particular systemic lupus erythematosus, systemic sclerosis, multiple sclerosis and type 1 diabetes mellitus. The aim of the procedure in autoimmune diseases is immune reprogramming. Apparently this procedure has indications for diseases in which conventional treatments have failed when organ damage is not definitive, but likely to occur if transplantation is not performed. The most promising method appears to be autologous stem cell transplantation with non-myeloablative conditioning regimens to obtain survival that is estimated at more than 50% for all autoimmune diseases, with low toxicity and no mortality related to transplantation. The controversial results of solid tumor treatment and particularities of breast cancer are also presented. Hematopoietic stem cell transplantation is the apparent indication for solid tumors based on intensive treatment with myeloablative doses in order to induce the graft versus tumor effect. The myeloablative conditioning regimens are introduced with the purpose of reducing the toxicity and inducing immunosuppression but the data are insufficient and questionable requiring the introduction of new therapeutic strategies based on cellular and immune therapy.

G-CSF is a FDA-approved drug, commonly utilized in neutropenic patients, long knows for its anti-inflammatory and angiogenic properties and also for its capacity to mobilize stem cells, hematopoiethic and endogen precursors and progenitor cells. Recently neuroprotective effects have been shown in animals and humans and there are publications mentioning its potential therapeutic role in focal ischemia (medial cerebral artery territory). We describe a case of a 74-year-old male patient, victim of a subarachnoid hemorrhage and brain ischemia due to bilateral involvement of medial cerebral arteries and vertebrobasilar vasospasms (overall ischemia), who was submitted to G-C5F therapy. G-CSF did not cause adverse effects, mobilized cells (as was seen by the exponential increase in leukocytes) and possibly contributed to a progressive clinical improvement confirmed using GCS and NIHSS scales. Clinical improvements did not reflect in eithrt CT, MNR or SPECT examinations. This initial experience opens the perspective for G-CSF studies in brain ischemia.