Glial reaction in the hippocampus after global cardiogenic ischemia

Many experimental surgerical procedures have been perfomed in the analyse of the phenomenon of brain trophism and plasticity, however undesirable intercorrence can occour leading to specific changes in the results that should be taken into attention. To study this issue we have promoted a transient cardiogenic interruption of the blood flow together with a transient occlusion of the bilateral common carotid arteries (2VO) in rats and analysed the state of activation of astrocyte and microglia by means of the glial fibrillary acidic protein (GFAP) and OX42 immunohistochemistry, respectively. Rats were submitted to incomplete global cerebral ischemia (IGCI) by occlusion of the bilateral carotid arteries for 30 minutes. During the IGCI surgical, some rats received a higher dose of the chloral hydrate anaesthesia which promoted a cardiogenic interruption of the blood flow (CIBF) for a period of 10 minutes followed by and prompt reperfusion. During that period, animals were submited to a cardiac massage and ventilated. Sham operation were made in control animals. Rats were killed and their brains processed 14 days after the surgery. The animals that have received a IGCI showed a slight astroglial and microglial reaction in all subfields of the hippocampal formation, however the animal submitted to CIBF showed a massive infiltration of the reactive astrocyte and microglia in CA1 subfield. This results demonstrated that a transient occlusion of the bilateral common carotid arteries leads to activation of glial cells in the hippocampus, however this response can be remarkable changed in animal developing a transient systemic hypoperfusion during surgery. Thus, an accurated monitoration of the hemodinamic condition of the animal has to be done in experimental models of brain ischemia and the results have to be analysed in view of this aspect. _____________________________________________________________________________________________________________________ RESUMOMuitos procedimentos experimentais são desenvolvidos para analisar o fenômeno do trofismo e plasticidade cerebral. Entretanto, eventos indesejáveis durante os procedimentos cirúrgicos podem ocorrer promovendo mudanças específicas nos resultados que devem ser levadas em consideração. Para estudar possibilidade, interrupção cardiogênica transitória do fluxo sangüíneo junto com a oclussão bilateral transitória das artérias caróridas comum (2VO) foi realizada em ratos e o estado de ativação de astrócitos e microglia foi analisado através da imunohistoquímica da proteína fibrilar ácida glial (GFAP) and OX42, respectivamente. Os ratos foram submetidos à isquemia cerebral global incompleta (IGCI) pela oclusão bilateral das artérias caróditas por 20 minutos. Durante o procedimento cirurgico da IGCI, alguns ratos receberam uma alta dose de anestésico de hidrato de cloral que promoveu uma interrupção cardiogênica do fluxo sangüíneo (CIBF) por um período de 10 minutos. Durante este período os ratos foram submetidos a massagem cardíaca e ventilados. Uma operação simulada foi realizada nos ratos controles. Os ratos foram mortos 14 dias após a cirurgia e seus cérebros processados para a imunohistoquímica. Os animais que receberam uma IGCI apresentaram uma leve reação astroglial e microglial em todos os sub-campos da formação hipocampal, entretanto os animais submetidos à CIBF mostraram uma infiltração massiça de astrócito e microglia reativos no sub-campo CA1. Estes resultados demonstram que oclusão bilateral transitória das artérias carótidas comum ativam as células gliais no hipocampo, entretanto esta resposta pode ser mudada substancialmente nos animais desenvolvendo hipoperfusão sistêmica durante o procedimento cirúrgico. Então, monitoramente acurado das condições hemodinâmicas do animal deve ser feito em modelos de isquemia cerebral e os resultados devem ser analisados em vista deste aspect

A estimulação elétrica funcional (FES) e a plasticidade do sistema nervoso central: revisão histórica

Estudos têm revelado modificações plásticas neuronais concomitantes a melhora clínica de pacientes portadores de lesões neurológicas e submetidos às terapias de estimulação, sugerindo que as respostas plásticas observadas no tecido neuronal podem refletir a recuperação funcional encontrada e ser dependentes, pelo menos em parte, da estimulação externa. A literatura já indica também que as terapias de reabilitação mais promissoras são aquelas que interagem com as características plásticas naturais do SNC, encontrando no potencial endógeno de recuperação do tecido lesado o substrato anatômico necessário para a sua atuação. A interpretação desses resultados permanece ambígua, já que há uma grande variabilidade nas respostas neurofisiológicas e comportamentais para as técnicas de estimulação estudadas. Nesse sentido, uma nova área de atuação surge como perspectiva futura promissora no entendimento dos mecanismos que regulam a recuperação funcional após lesões neurológicas: o uso terapêutico da estimulação da plasticidade do SNC. Por exemplo com o uso de terapias de estimulação sensitiva, terapias baseadas na robótica e na realidade virtual e as terapias de neuromodulação baseadas na estimulação cortical direta, na estimulação com o TMS e na estimulação elétrica funcional periférica (FES). Objetivo: Este estudo tem por objetivo realizar uma revisão histórica da literatura para pontuar os principais marcos no estudo da estimulação elétrica periférica e de seus possíveis efeitos no SNC, sobretudo em relação a FES. Método: Foi utilizada a base de dados PubMed e foram selecionados 169 artigos de melhor rigor metodológico, maior relevância histórica e maior contribuição na construção dos paradigmas que norteiam o estudo dos efeitos da FES na plasticidade do sistema nervoso central. Resultados: A FES pode ser encarada como uma técnica promissora na recuperação motora de doentes com sequela de alterações neurológicas de origem central tanto pela sua capacidade de levar a um treino funcional e melhora clínica sensitivomotora, aspectos já consagrados na literatura, quanto pela sua capacidade de interagir com a plasticidade do SNC, um aspecto que ainda precisa ser estudado.Neurophysiological imaging studies have revealed changes in the pattern of cortical structures and clinical functionality during recovery after brain lesion, thus suggesting a correlation between clinical functional improvements and the plastic changes of the neuronal tissue. However, the interpretation of these results remains equivocal. Importantly, therapeutic neuronal stimulation leading to neurorehabilitation gains and is able to trigger endogenous nervous system changes that may interact with normal learning. In this way, stimulation of the endogenous CNS neuroplasticity as an anatomical substrate for neuronal functional recovery has emerged as a promising area in the search for understanding the mechanisms that regulate functional recovery after brain lesion. Objective: This study aims to review historical literature to score major milestones in the study of peripheral electrical stimulation and their possible effects on the CNS, particularly in relation to functional electrical stimulation. Method: This review was drawn from an examination of the historical literature articles researched at MedLine®, the National Library of Medicine’s database. We selected 169 studies based on historical relevance, importance, and accuracy. Results: FES has the ability to interact with the CNS. The extent to which compensatory plasticity occurs after stroke after FES use and the extent to which that contributes to functional recovery are as yet unclear. Nevertheless, further investigations are warranted for evaluating the effect of FES on cortical structural modifications

Modulation of Tyrosine Hydroxylase, Neuropeptide Y, Glutamate, and Substance P in Ganglia and Brain Areas Involved in Cardiovascular Control after Chronic Exposure to Nicotine

Considering that nicotine instantly interacts with central and peripheral nervous systems promoting cardiovascular effects after tobacco smoking, we evaluated the modulation of glutamate, tyrosine hydroxylase (TH), neuropeptide Y (NPY), and substance P (SP) in nodose/petrosal and superior cervical ganglia, as well as TH and NPY in nucleus tractus solitarii (NTS) and hypothalamic paraventricular nucleus (PVN) of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after 8 weeks of nicotine exposure. Immunohistochemical and in situ hybridization data demonstrated increased expression of TH in brain and ganglia related to blood pressure control, preferentially in SHR, after nicotine exposure. The alkaloid also increased NPY immunoreactivity in ganglia, NTS, and PVN of SHR, in spite of decreasing its receptor (NPY1R) binding in NTS of both strains. Nicotine increased SP and glutamate in ganglia. In summary, nicotine positively modulated the studied variables in ganglia while its central effects were mainly constrained to SHR

Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy

<p>Abstract</p> <p>Background</p> <p>The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system.</p> <p>Methods</p> <p>Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg^-1). Animals were sacrificed seven days later.</p> <p>Results</p> <p>Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction.</p> <p>Conclusion</p> <p>FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.</p

Behavioral Improvement and Regulation of Molecules Related to Neuroplasticity in Ischemic Rat Spinal Cord Treated with PEDF

Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins

IL-12p40 Deficiency Leads to Uncontrolled Trypanosoma cruzi Dissemination in the Spinal Cord Resulting in Neuronal Death and Motor Dysfunction

Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently shows severe chronic clinical complications of the heart or digestive system. Neurological disorders due to T. cruzi infection are also described in children and immunosuppressed hosts. We have previously reported that IL-12p40 knockout (KO) mice infected with the T. cruzi strain Sylvio X10/4 develop spinal cord neurodegenerative disease. Here, we further characterized neuropathology, parasite burden and inflammatory component associated to the fatal neurological disorder occurring in this mouse model. Forelimb paralysis in infected IL-12p40KO mice was associated with 60% (p&lt;0.05) decrease in spinal cord neuronal density, glutamate accumulation (153%, p&lt;0.05) and strong demyelization in lesion areas, mostly in those showing heavy protein nitrosylation, all denoting a neurotoxic degenerative profile. Quantification of T. cruzi 18S rRNA showed that parasite burden was controlled in the spinal cord of WT mice, decreasing from the fifth week after infection, but progressive parasite dissemination was observed in IL-12p40KO cords concurrent with significant accumulation of the astrocytic marker GFAP (317.0%, p&lt;0.01) and 8-fold increase in macrophages/microglia (p&lt;0.01), 36.3% (p&lt;0.01) of which were infected. Similarly, mRNA levels for CD3, TNF-alpha, IFN-gamma, iNOS, IL-10 and arginase I declined in WT spinal cords about the fourth or fifth week after infection, but kept increasing in IL-12p40KO mice. Interestingly, compared to WT tissue, lower mRNA levels for IFN-gamma were observed in the IL-12p40KO spinal cords up to the fourth week of infection. Together the data suggest that impairments of parasite clearance mechanisms in IL-12p40KO mice elicit prolonged spinal cord inflammation that in turn leads to irreversible neurodegenerative lesions.FAPESPFAPESPCAPESCAPESCNPqCNP