ABSTRACT
Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.
Subject(s)
Apoptosis , Cytokines/therapeutic use , Apoptosis/physiology , Cytokines/pharmacokinetics , Cytokines/physiology , Glaucoma/physiology , Humans , Intraocular Pressure/drug effects , Nerve Degeneration/physiology , PubMed/statistics & numerical data , Retinal Artery Occlusion , Retinal Ganglion Cells/drug effects , Review Literature as Topic , Tumor Necrosis Factor-alpha/pharmacokinetics , Tumor Necrosis Factor-alpha/physiologyABSTRACT
It has been established that neurons exposed to high concentrations of glutamate or other excitatory amino acids degenerate and die. Neuronal damage appears to be due to the activation of different types of glutamate receptors, among which the ionotropic N-methyl-D-aspartate (NMDA) type seems particularly involved, since its channel is permeable to Ca2+ and an increase in the cytoplasmic concentration of this cation promotes a chain of events leading to cell death. The mechanism of such glutamate receptor-mediated neurodegeneration has been defined as excitotoxicity, and several pieces of evidence suggest that this mechanism might contribute to the neuronal death associated with certain neurological disorders, such as ischemia, cerebral trauma and some chronic neurodegenerative diseases. A relevant question is whether the origin of endogenous extracellular glutamate is important for the induction of excitotoxicity. An excess of glutamate release, or a deficiency in its clearance from the synaptic cleft, which depends mainly on its transport by high affinity carriers, are potential sources for the accumulation of extracellular glutamate. In the present article some experimental results from our laboratory, aimed at obtaining information on this question, are reviewed. These experiments include the use of 4-aminopyridine, a convulsant drug that enhances the release of glutamate, and of some inhibitors of glutamate transport, in vivo and in neuronal cell cultures. The results obtained indicate that an increase of endogenous extracellular glutamate due to these procedures is not sufficient to induce neuronal death, at least under the experimental condition used.
Subject(s)
4-Aminopyridine/adverse effects , Cell Culture Techniques , Glutamic Acid/physiology , Glutamic Acid/toxicity , In Vitro Techniques , N-Methylaspartate/physiology , Nerve Degeneration/physiologyABSTRACT
Mujer de 60 años, quien se volvió inquieta, con delirios de asaltos a su casa, que en el espacio de 6 meses fueron reemplazados progresivamente por apatía. Se notó pérdida progresiva de la memoria y desorientación, que progresó hacia la demencia profunda y caquexia en el espacio de 30 meses. La TAC mostró una atrofia moderada y simétrica que afectaba a todo el cerebro pero más intensamente a los lóbulos frontales. Se realizó biopsia cerebral
Subject(s)
Aged , Humans , Female , Alzheimer Disease/pathology , Cerebral Cortex/cytology , Cerebral Cortex/pathology , Nerve Degeneration/physiology , Cerebral Ventricles/cytology , Cerebral Ventricles/pathologyABSTRACT
A síndrome de Guillain-Barré "axonal" caracteriza-se por uma apresentaçäo clínica semelhante à das neuropatias inflamatórias desmielinizantes agudas, distinguindo-se destas pela rapidez de evoluçäo, gravidade e mau prognóstico. Duas säo as possibilidades fisiopatológicas; degeneraçäo axonal distal ou lesäo desmilinizante distal. O autor apresenta uma revisäo dos principais aspectos da literatura
Subject(s)
Humans , Polyradiculoneuropathy/physiopathology , Axons/physiology , Nerve Degeneration/physiology , Demyelinating Diseases/physiopathology , Electromyography , Neuromuscular Junction/physiology , Polyradiculoneuropathy/complications , Polyradiculoneuropathy/diagnosisABSTRACT
Neste trabalho säo revisados os aspectos básicos da anatomia macro e microscópica e os principais aspectos da fisiologia dos nervos periféricos, bem como a fisipatologia (regeneraçäo e degeneraçäo) das lesöes traumáticas agudas destes nervos, com o objetivo de facilitar o entendimento da indicaçäo dos tratamentos conservador e/ou cirúrgico destas lesöes. As evidências clínicas e eletrofisiológicas de degeneraçäo säo apresentadas e o momento de exploraçäo cirúrgica é discutido baseado no tempo decorrido desde a lesäo e a possibilidade de regeneraçäo espontânea no período correspondente
Subject(s)
Humans , Peripheral Nerves/injuries , Peripheral Nervous System Diseases , Nerve Degeneration/physiology , Peripheral Nervous System Diseases/surgery , Peripheral Nervous System Diseases/classification , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nerves/anatomy & histology , Peripheral Nerves/physiology , Nerve Regeneration/physiologyABSTRACT
É apresentado o caso de um paciente brasileiro com degeneraçäo córtico-ganglionar basal (DCGB). Há três anos um homem de 71 anos de idade apresenta-se com apraxia ideomotora, apraxia de marcha, déficit sensitivo cortical, rigidez mioclonias e distonia apendicular. Todos estes sinais säo assimétricos. Seu estado mental está preservado. Näo há consanguinidade ou casos semelhantes na família. O diagnóstico diferencial desta nova entidade é discutido. Também é feita breve revisäo da literatura, dando ênfase aos aspectos clínicos e patológicos da DCGB. Esta doença é mal conhecida e, possivelmente, pouco diagnosticada. O diagnóstico pode ser feito, com segurança, baseado em dados clínicos
Subject(s)
Humans , Male , Aged , Cerebral Cortex/pathology , Nerve Degeneration/physiology , Basal Ganglia/pathology , Apraxias/physiopathologyABSTRACT
This study was designed to test the effects of simultaneous deafferentation and target removal on cell death in the parabigeminal nucleus. Bilateral lesions of the superior colliculus were made in newborn rats and neuron death was evaluated in the dorsal (PBd), middle (PBm) and ventral PBv) division of the nucleous. When the results of the bilateral lesions were compared with the effects of unilateral lesions reported in a previous study simultaneous deafferentation and tarfet removal were found to produce an increase in the rate of cell death greater than, and with a time course differing from that, predicted by the sun of the separate effects of removal of afferents or targets. These data suggest that the trophic effects of afferents and targets interact during the period of naturally occurring cell death
Subject(s)
Rats , Animals , Nerve Degeneration/physiology , Neurons, Afferent/physiology , Superior Colliculi/physiology , Cell Communication , Cell Death/physiologyABSTRACT
Técnicas de neurofisiologia clínica aplicadas em 41 pacientes com as várias formas clínicas da doença de Chagas demonstraram haver correlaçäo entre as formas clínicas da doença e a intensidade da desnervaçäo muscular periférica. Os pacientes com a forma cárdio-digestiva mostraram intensa desnervaçäo; aqueles das formas cardíaca e digestiva (puras), moderada desnervaçäo; os da forma indeterminada, discreta desnervaçäo. Neuropatia periférica tipo axonal foi observada acompanhando a mesma distribuiçäo da desnervaçäo de músculos esqueléticos (motora). Já a intensidade da desnervaçäo näo mostrou relaçäo direta com a gravidade das manifestaçöes clínicas