Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs / Neuroinflamação na patofisiologia da doença de Parkinson e evidências terapêuticas de drogas antiinflamatórias

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum afetando aproximadamente 1,6% da população acima de 60 anos de idade. Os sinais motores cardinais são o resultado da degeneração progressiva de neurônios dopaminérgicos da substantia nigra pars compacta (SNpc), a qual está intimamente envolvida com o controle motor. Atualmente, não há cura para esta patologia e a causa da neurodegeneração permanece desconhecida. Contudo, muitos estudos sugerem o envolvimento da neuroinflamação na patofisiologia da DP bem como um efeito protetor de drogas antiinflamatórias tanto em modelos animais quanto em estudos epidemiológicos, embora haja relatos controversos. Nesta revisão, foram abordadas evidências de envolvimento do processo inflamatório e uma possível utilidade terapêutica de drogas antiinflamatórias na DP.

El uso de placebo en ensayos clínicos de fase III en Brasil / The use of placebos in phase III clinical trials in Brazil

El Consejo Federal de Medicina de Brasil (CFM) -órgano normativo y fiscalizador del ejercicio ético de la medicina- prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase III en Brasil, se analizaron varias características de sus registros en el ClinicalTrials.gov, en los períodos de 2003 a 2007 y de 2009 a 2013. Se concluye que: a) la normativa promulgada por el CFM en 2008 fue ineficaz y prevaleció la posición adoptada por la Declaración de Helsinki; b) el patrocinio de ensayos con placebo por parte de la industria farmacéutica multinacional fue significativo; c) predominaron las investigaciones de fármacos para enfermedades crónicas, y fueron poco significativas para las enfermedades postergadas, de importancia para Brasil.

In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina] (CFM) - regulatory and supervisory agency on the ethical practice of medicine - banned the participation of Brazilian doctors in studies using placebos for diseases with efficient and effective treatment. This position differs with the Helsinki Declaration, which allows the use of placebos in methodologically justified conditions. To ascertain whether the CMF's ethical regulation modified the use of placebos in phase III clinical trials in Brazil, characteristics of the records in ClinicalTrials.gov were researched in the periods from 2003 to 2007 and from 2009 to 2013. The conclusions reached were: a) the regulations issued by the CFM in 2008 were ineffective and the position adopted by the Helsinki Declaration prevails; b) there was significant sponsorship by the multinational pharmaceutical industry of trials with placebos; c) the research was predominantly on new drugs for chronic diseases, with little study done of the neglected diseases which are of great importance to Brazil.

Consecuencias de la enfermedad de Parkinson en la calidad de vida / Consequences of Parkinson’s disease on quality of life

La enfermedad de Parkinson (EP), se identifica como una enfermedad neurodegenerativa, que tiende a atacar al Sistema Nervioso Central, dañando severamente regiones neuronales de la sustancia negra. A nivel mundial la EP ocupa la segunda posición como la enfermedad de degeneración neuronal con mayor prevalencia. Los orígenes de la EP resultan multifactoriales, pues al presente se desconoce una única causa biológica o genética que explique su etiología de forma plena y satisfactoria. Se reconocen en la actualidad una variedad de siete tipos de Parkinsonismo, que producen afectaciones en sus distintas etapas, tanto a nivel de los sistemas de serotonina, noradrenalina como acetilcolina. Los drásticos efectos que provoca la EP sobre la Calidad de Vida (CV) de los pacientes, puede ser evaluada científica y cuantitativamente, desde las múltiples pruebas y evaluaciones que han surgido dentro del campo de las ciencias de la salud. Los cuatro síntomas más comunes para el reconocimiento del Parkinsonismo, son la inestabilidad postural, la rigidez corporal, la bradicinesia y los temblores. La EP continúa siendo poco intervenida en sus etapas tempranas de aparición, especialmente en naciones en vías de desarrollo, por lo que se requiere mayor unidad entre disciplinas científicas y sistemas públicos de salud, para mejorar la CV de estas poblaciones...

Parkinson's disease (PD), is identified as a neurodegenerative disease, tending to attack the Central Nervous System, severely damaging neural regions of substantia nigra. Globally PD ranks second as the most prevalent neuronal degeneration disease. The origins of PD are multifactorial, because nowadays a unique biological or genetic cause to explain the etiology of full and satisfactory way is unknown. They now recognize a variety of seven types of Parkinsonism, producing affectations in its various stages, both at the serotonin, norepinephrine and acetylcholine systems. The drastic effects caused by PD on Quality of Life (QoL) of patients, can be evaluated quantitatively and scientifically and from the multiple tests and evaluations that have emerged within the field of health sciences. The four most common symptoms of Parkinsonism recognition are postural instability, body rigidity, bradykinesia and tremors. PD is still little intervened in the early stages of emergence, especially in developing nations, so that greater unity between scientific disciplines and public health systems are required to improve the QoL’s populations...

Limb immobilization alters functional electrophysiological parameters of sciatic nerve

Immobilization, used in clinical practice to treat traumatologic problems, causes changes in muscle, but it is not known whether changes also occur in nerves. We investigated the effects of immobilization on excitability and compound action potential (CAP) and the ultrastructure of the rat sciatic nerve. Fourteen days after immobilization of the right leg of adult male Wistar rats (n=34), animals were killed and the right sciatic nerve was dissected and mounted in a moist chamber. Nerves were stimulated at a baseline frequency of 0.2 Hz and tested for 2 min at 20, 50, and 100 Hz. Immobilization altered nerve excitability. Rheobase and chronaxy changed from 3.13±0.05 V and 52.31±1.95 µs (control group, n=13) to 2.84±0.06 V and 59.71±2.79 µs (immobilized group, n=15), respectively. Immobilization altered the amplitude of CAP waves and decreased the conduction velocity of the first CAP wave (from 93.63±7.49 to 79.14±5.59 m/s) but not of the second wave. Transmission electron microscopy showed fragmentation of the myelin sheath of the sciatic nerve of immobilized limbs and degeneration of the axon. In conclusion, we demonstrated that long-lasting leg immobilization can induce alterations in nerve function.

Mecanismos de neurodegeneración en la epilepsia del lóbulo temporal / Mechanisms of neurodegeneration in temporal lobe epilepsy

Epilepsy affects 1 and 2 percent of the worldwide population, while temporal lobe epilepsy (TLE) covers 40 percent of all epilepsy cases. Controversy in defining epilepsy as a neurodegenerative disease exists because, no there is enough evidence to show seizures and status epilepticus (SE) as cause for irreversible neuronal damage. Epileptogenic insult at the beginning of the disease produces an acute and delayed neuronal death, resulting in gliosis, but also triggers compensatory processes such as angiogenesis, cell proliferation and reorganization of extracellular matrix as receptors, channels and drug transporter proteins. In neurogenesis and axonal regrowth, the age of onset is crucial for the formation of abnormal neurons and aberrant circuits as a result of seizures; approximately 30 percent begin in the temporal lobe. These disturbances continue in parallel or sequentially during the course of epilepsy, which implies a great challenge in the search of new treatments...

La epilepsia es una enfermedad que afecta entre el 1 al 2 por ciento de la población mundial, siendo la epilepsia del lóbulo temporal (ELT) la que abarca el 40 por ciento de todos los casos de epilepsia. La controversia en definir a la epilepsia como una enfermedad neurodegenerativa, se debe a que no hay pruebas suficientes que demuestren como las convulsiones y el estado de mal epiléptico (SE) provocan un daño neuronal irreversible. El insulto epileptógenico presente al inicio de la enfermedad genera la muerte neuronal aguda y tardía, para dar lugar a la gliosis; pero también se desencadenan procesos compensatorios como la angiogénesis, la proliferación celular y una reorganización tanto de la matriz extracelular como de los receptores, canales y proteínas transportadoras de fármacos. En el caso de la neurogénesis y recrecimiento axonal, la edad de inicio es determinante para la formación de neuronas anormales y circuitos aberrantes como consecuencia de las convulsiones, dónde aproximadamente un 30 por ciento comienzan en el lóbulo temporal. Estas alteraciones se continúan en paralelo o de forma secuencia! durante la evolución de la epilepsia, lo que implica un gran desafío en la búsqueda de nuevos tratamientos...

Pathophysiology of neurodegeneration following traumatic brain injury / Patofisiología de la neurodegeneración tras una lesión traumática del cerebro

Acute neuropathological conditions, including brain and spinal cord trauma, are leading causes of death and disabilities worldwide, especially in children and young adults. The causes of brain and spinal cord injuries include automobile accidents, accidents during recreational activities, falls and violent attacks. In the United States of America alone, around 1.7 million people each year seek medical care for some kind of head injury. About fifty-two thousand of these people will die, while the same number will present with permanent functional disability. Considering the high worldwide prevalence of these acute pathological conditions, research on the mechanisms underlying central nervous system damage is of extreme importance. Nowadays, a number of experimental models of acute neural disorders have been developed and the mechanisms of tissue loss have been investigated. These mechanisms include both primary and secondary pathological events contributing to tissue damage and functional impairment. The main secondary pathological mechanisms encompass excitotoxicity, ionic imbalances, inflammatory response, oxidative stress and apoptosis. The proper elucidation of how neural tissue is lost following brain and spinal cord trauma is fundamental to developing effective therapies to human diseases. The present review evaluates the main mechanisms of secondary tissue damage following traumatic brain and spinal cord injuries.

Las condiciones neuropatológicas agudas, incluyendo los traumas del cerebro y la médula espinal, se hallan entre las principales causas de muerte y discapacidades a nivel mundial, sobre todo en niños y adultos jóvenes. Las causas de las lesiones del cerebro y la médula espinal, incluyen los accidentes automovilísticos, accidentes en actividades recreativas, caídas y ataques violentos. Sólo en los Estados Unidos de Norte América, alrededor de 1.7 millones de personas buscan anualmente atención médica para algún tipo de lesión craneal. Cincuenta y dos mil de estas personas morirán, mientras que un número similar presentará alguna discapacidad funcional permanente. Dada la alta prevalencia de estas condiciones patológicas agudas a nivel mundial, la investigación de los mecanismos que subyacen en los daños al sistema nervioso central, constituye un asunto de suma importancia. Hoy día, se han desarrollado varios modelos experimentales de trastornos neurales agudos, y se han investigado los mecanismos de la pérdida de tejido. Estos mecanismos incluyen tanto las manifestaciones patológicas primarias como las secundarias, que contribuyen al daño del tejido y al deterioro funcional. Los mecanismos patológicos secundarios principales abarcan la excitotoxicidad, los desequilibrios iónicos, la respuesta inflamatoria, el estrés oxidativo, y la apoptosis. Dilucidar correctamente como ocurre la pérdida del tejido neuronal luego del trama del cerebro o la médula espinal, es fundamental para poder desarrollar terapias efectivas en relación con las enfermedades humanas. La presente revisión evalúa los mecanismos principales del daño secundario al tejido, tras las lesiones traumáticas del cerebro y la médula espinal.

Potential of immunosuppressive agents in cerebral ischaemia.

Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.

Unconventional neurotransmitters, neurodegeneration and neuroprotection

Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death.

Aspectos fisiológicos do cálcio e sua disfunção em patologias neurodegenerativas / Physiologic aspects of calcium and your dysfunction in neurodegenerative pathologies

O íon cálcio funciona como um segundo mensageiro que regula um amplo espectro de processos celulares. A diminuição ou perda do controle dos mecanismos que regulam a concentração intracelular desse íon está associada, respectivamente, ao envelhecimento dos neurônios e a doenças neurodegenerativas. A gênese dessas modificações é desconhecida. Entretanto, estudos recentes apontam para uma provável correlação entre expressão gênica alterada, estresse do retículo endoplasmático e os processos patológicos associados à disfunção na concentração intracelular do cálcio. O esclarecimento dessas questões poderá trazer novos alvos terapêuticos capazes de frear ou reverter tais alterações, combatendo, dessa forma, tanto o envelhecimento neuronal quanto as doenças neurodegenerativas.

Calcium is a second messenger that regulates a lot of cellular functions. The following mechanisms regulate the intracellular concentrations of the ion: influx, release, extrusion and storage. Decrease or loss in control of these mechanisms is related to aging of neurons and neurodegenerative diseases, respectively. The genesis of these alterations is unknown. However, recent studies point to a correlation between calcium dysfunction and altered gene expression. There is also a correlation between endoplasmic reticulum stress and pathological processes. Further investigations may reveal new therapeutical targets that can block or revert these alterations.

Ultrastructural changes of the epineurial and endoneurial fibroblasts in diabetic rats

Peripheral neuropathy can be produced by several diseases, the most common of which is diabetes mellitus. Diabetic neuropathy is a degenerative complication of diabetes mellitus. It is a disease reversible with treatment and is characterized by attacks of degeneration of the peripheral nerves alternating with nerve regeneration but its mechanisms remain poorly understood. A variety of mechanisms have been implicated in the pathogenesis and progression of peripheral diabetic neuropathy. The epineurium and the endoneurium of the peripheral nerves contain fibroblasts which form the collagen fibrils. It was recorded that theses fibroblasts showed several structural and morphological changes in different types of nerve injuries and peripheral neuropathy. Was to study the ultrastructural changes in the epineurial and endoneurial fibroblasts in diabetic neuropathy. Twelve albino rats with streptozotocin-induced diabetes and six control rats were used. The sciatic nerves were processed and examined using transmission electron microscope. The epineurial fibroblasts were increased in number and possessed cytoplasmic processes which were in direct contact with each other and with the epineurial mast cells stimulating these cells to release their granules with increased epineurial vascular permeability and macrophage infiltration with the release of cytokines that participate at nerve damage and others that promote nerve regeneration. The epineurial fibroblasts showed interruptions of their membranes indicating the sites of exocytosis of the newly formed collagen fibrils into the epineurium. The endoneurial fibroblasts showed branching cytoplasmic processes which may be used in the phagocytosis of the degenerated myelin in the diabetic nerves and also to separate the newly formed nerve fibers from the endoneurial edema. These fibroblasts also released ciliary neurotropic factor that improves nerve conduction and regeneration. They also showed cytoplasmic vacuoles of different sizes or shapes. Some of these vacuoles contained electron lucent substances suggested to be nerve growth factors to promote regeneration while others contained electron dense membrane suggested to be degenerated myelin. The endoneurial fibroblasts formed several parallel layers in the subperineurial space to separate the nerve fibers from the endoneurial edema. The increase in the epineurial and endoneurial fibroblasts in the diabetic nerves could be beneficial in nerve fibers regeneration

Compromiso neuronal en esclerosis multiple / Neuronal injury in multiple sclerosis

La esclerosis múltiple (EM) ha sido considerada clásicamente como una enfermedad desmielinzante. Si bien el compromiso neurodegenerativo fue previamente descripto, sólo recientemente ha sido enfatizado. Por estudiosos recientes se ha identificado la degeneración axonal como el mayor determinante de discapacidad neurológica irreversible en pacientes con EM. El daño axonal se inicia tempranamente y permanece silente durante años, la discapacidad neurológica se desarrolla cuando se alcanza cierto umbral de pérdida axonal y los mecanismos de compensación se agotan. Se han propuesto tres hipótesis para explicar el daño axonal: 1) El daño es causado por un proceso inflamatorio, 2) Existe una excesiva acumulación de Ca2+ intra-axonal, 3) Los axones desmienlinizados evolucionan a un proceso degenerativo producto de la falta de soporte trófico provisto por la mielina o células formadoras de mielina. Si bien la EM fue tradicionalmente considerada como una enfermedad de la sustancia blanca, el proceso de desmielinización tambiém ocurre en la corteza cerebral

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment

Mecanismos neurobiológicos de la enfermedad de Alzheimer / Neurobiological mechanisms of Alzheimer's disease

En la medida que entendemos mejor la complejidad de la Enfermedad de Alzheimer, se revelan las bases biológicas subyacentes de su patogénesis, apareciendo nuevos blancos terapéuticos. Muchos agentes que son investigados en estos momentos apuntan a las etapas tempranas de la enfermedad. Su objetivo es prevenir o al menos retardar la progresión hacia la aparición del déficit clínico. Sin embargo, uno de los problemas que enfrenta la investigación en el área, es lograr distinguir entre los eventos primarios y secundarios. Los mecanismos patológicos involucrados consideran las diversas acciones del beta-amiloide, incluyendo la acumulación de agregados, la cascada inflamatoria, el daño oxidativo neuronal, alteraciones de la proteína tau y la formación de ovillos neurofibrilares, defectos sinápticos y depleción de neurotransmisores. Muchos de estos eventos son comunes para numerosos desórdenes neurodegenerativos de progresión lenta. Las formas familiares del Alzheimer, secundarias a mutaciones hereditarias, han ofrecido una aproximación para el análisis de los mecanismos moleculares implicados en la patogénesis de la enfermedad. Usando la Enfermedad de Alzheimer familiar como punto de partida, intentaremos avanzar en nuestra comprensión de los otros mecanismos biológicos envueltos en la neurodegeneración de la enfermedad.

As our understanding of the complexity of Alzheimer’s disease improves, the biological bases underlying its pathogenesis are gradually being disclosed, and we can expect that new therapeutic targets will emerge. Many agents under investigation at this moment target the early stages of the disease process. Their aim is to prevent or at least slow down the progression towards clinica limpairment. However, one of the problems research face is the distinction between primary and secondary events. The pathological mechanisms involved include the actions of beta-amyloid, the accumulation of aggregates, the inflammatory cascade, oxidative neuronal damage, tau protein alterations and the formation of neurofibrillary tangles, synaptic failure and neurotransmitter depletion. Several of these events are common to many slowly progressive neurodegenerative disorder. The familial forms of Alzheimer’s, secondary to inherited mutations have provide an insight into the molecular mechanisms implicated in disease pathogenesis. Using as an starting point familial Alzheimer’s disease, we will work our way up to understand the other biological mechanisms involved in the neurodegeneration of the disease.

Mensuração da força de preensão palmar em pacientes portadores de hanseníase atendidos em nível ambulatorial / Mensuration of palmar prehension strength in hansen's disease patients treated in ambulatorial level

O comprometimento neural é considerado o principal fator fisiopatogênico de todas as formas clínicas da hanseníase. Observa-se que a força de preensão palmar encontra-se comprometida como conseqüência do dano neural. O objetivo do presente estudo foi o de mensurar a força de preensão palmar em um delineamento observacional, onde 50 pacientes portadores de hanseníase foram estudados e comparados com 50 indivíduos saudáveis. Durante a mensuração da força de preensão palmar utilizou-se o dinamômetro hidráulico de mão - Jamar®. Os resultados obtidos mostraram que houve diferença estatisticamente significativa entre os grupos estudados (p<0,05). Conclui-se que existe uma tendência à fadiga muscular da força de preensão palmar em pacientes portadores de hanseníase, mesmo que se estabeleça intervalos de descanso entre as repetições

Comparison of nerve graft integration after segmentar resection versus epineurial burying in crushed rat sciatic nerves

The aim of the present paper is to compare and correlate the take of nerve segments in a severely crushed nerve. Forty adult Wistar rats had their right sciatic nerve crushed by a "Péan-Murphy" forceps for 40 minutes. In Group 1 (n=20), a segmentar resection in the crushed sciatic nerve was made. A sural nerve segment from the opposite hindpaw was placed in the gap. In Group 2 (n=20), a longitudinal incision in the epineurium of the lesioned sciatic nerve was made. A sural nerve segment was buried underneath the epineurium. The crushed sciatic nerves undergone Wallerian degeneration and endoneurial fibrosis. Sciatic nerves from Group 2 had significant better histological aspects than those from Group 1. Sural nerve grafts presented better degrees of regeneration than crushed sciatic nerves. Sural nerve grafts from Group 2 (burying method) integrated as well as those from Group 1 (segmentar resection).

Unilateral enucleation induces an increase of 160 kd neurofilament in lateral geniculate nuclei synapses

Ultrastructural synaptic changes of retinal origin in the pars dorsalis lateral geniculate nuclei (dLGN) after enucleation have been studied in this laboratory, showing a filamentous hypertrophy with maximal expression at 4-6 days post-lesion in monkeys (Pecci Saavedra et al., 1970, 1971). The aim of this work was to elucidate the nature of the newly formed filament in dLGN in post-enucleated rats. Male Wistar rats were fixed with 4 paraformaldehyde plus 0.25 glutaraldehyde in 0.1M phosphate buffer, through the abdominal aorta after 3, 5, and 7 days postenucleation. Sections obtained were incubated with antibodies to the phosphorylated portion of the 160 Kd neurofilaments (1:3000) and anti-GFAP (1:25000). There was an increase in 160 Kd neurofilament staining in axons and degenerating nerve endings in dLGN, as well as a typical astroglial immunostained reaction. Our results show that the newly formed neurofilaments after deafferentation are of the 160 Kd type, commonly present in normal axons.