Alfonso Escobar

Cysticercosis and epilepsy: a critical review.

Summary: Neurocysticercosis (NC) remains a major public health problem in developing and some developed countries. Currently, the best procedures for diagnosing NC are neuroimaging studies. Immunoserologic assays, such as enzyme‐linked immunoelectrotransfer blot assay (EITB) or enzyme‐linked immunosorbent assay (ELISA), detect antibodies against Taenia solium, or cysticercus. Consequently, they are useful in identifying a population at risk of contact with the parasite but do not necessarily indicate a systemic active infection. Most seropositive individuals are asymptomatic. No data from prospective studies concern the proportion of these individuals that will develop seizures or other neurologic symptoms. There is a discrepancy between the results of serologic assays and neuroimaging studies: >50% of those individuals with NC diagnosed by computed tomography (CT) scan test EITB negative.

Neuroprotective effects of progesterone on damage elicited by acute global cerebral ischemia in neurons of the caudate nucleus.

BACKGROUND In addition to the hippocampus, the dorsolateral caudate nucleus (CN) and the pars reticularis of the substantia nigra (SNr) are among the most vulnerable brain areas to ischemia. A possible association of the neuronal injury in these two subcortical nuclei has been proposed, the primary damage affecting the CN GABAergic neurons innervating the SNr, and secondarily the SNr neurons as a result of an imbalance of GABAergic and glutamatergic input to the SNr. Progesterone (P(4)) exerts a GABAergic action on the central nervous system (CNS) and is known to protect neurons in the cat hippocampus from the damaging effect of acute global cerebral ischemia (AGCI). The effects of AGCI on the neuronal populations of the CN and SNr, in addition to the possible neuroprotective effects of P(4), were assessed in cats in the present study. METHODS Ovariectomized adult cats were treated subcutaneously (s.c.) with either P(4) (10 mg/kg/day) or corn oil during the 7 days before and 7 days after being subjected to a period of AGCI by 15 min of cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of survival, animals were sacrificed and their brains perfused in situ with phosphate-buffered 10% formaldehyde for histologic examination. RESULTS ACGI resulted in an intense glial reaction in the CN and a significant loss (43%) of medium-sized neurons of the CN, but no difference was found in the densities of SNr neurons between controls and ischemic oil- and P(4)-treated cats. Progesterone treatment completely prevented CN neuronal loss. CONCLUSIONS The overall results point to the higher vulnerability of CN neurons to ischemia as compared to neurons in the SNr and show the protective effects of P(4) upon CN neuronal damage after ischemia.

A proposal for classification of neurocysticercosis.

The complicated pathophysiological and immunological changes in the central nervous system of patients with neurocysticercosis produce a variety of signs and symptoms, which complicate the clinical and surgical management of this disease. A complete and objective classification is needed, to improve the medical approach as a whole. We studied 336 patients, in whom we classified neurocysticerosis according to criteria of viability and location of the parasite in the CNS: active form (37.2%) when the cysticercus is alive, transitional form (32.8%) when it is in the degenerative phase, and inactive form (30%) when the parasite is dead. This classification establishes the correlation between the different forms of neurocysticerosis and its clinical manifestations, and can be used for planning therapeutic strategies.

Clinical heterogeneity of human neurocysticercosis results from complex interactions among parasite, host and environmental factors

Human neurocysticercosis (NC) is endemic in most countries of Latin America, Asia and Africa and is re-emerging in some industrialized nations. Both within and among endemic countries, NC is very variable in its clinical and radiological features, as well as in the intensity of the immuno-inflammatory reactions of the hosts. This review, focusing on the Mexican experience, describes and interprets the heterogeneity of NC as the result of different combinations among factors associated with the parasite, host and environment. The review may serve to foster similar descriptive efforts in other endemic areas of the world in order to facilitate the identification of the distinct factors that participate in the complex pathogenesis and diverse clinical outcomes of NC. In particular, it is necessary to understand the precise physiopathology of the inflammatory reaction associated with NC, as inflammation is one of the characteristics of those NC cases that are clinically more severe and less responsive to current treatments. Devising new medical interventions through the use of molecular regulators of the innate and adaptive immune responses of the host is a largely unexplored approach that could improve the existing forms of treatment.

Fullerene C60 and ascorbic acid protect cultured chromaffin cells against levodopa toxicity

Adrenal chromaffin cell (ACC) transplants, alone or combined with levodopa treatment, were used in attempted therapy for Parkinsons disease (PD). In a previous study, we demonstrated that levodopa caused chromaffin cell death either by necrosis or by apoptosis in cell culture. Here we report the beneficial effect of a water‐soluble derivative of fullerene C60 (a novel molecule with potent antioxidant properties) and of ascorbic acid when applied to chromaffin cell cultures exposed to levodopa. Both antioxidants remarkably increase the ACC survival and prevent cell death, including apoptosis. Although ACC transplants are not currently considered as an option for PD treatment, these observations should help in exploring the possibilities of preventing the neurotoxicity generated by levodopa and in envisaging new strategies for PD treatment by combining the clinical use of levodopa and potent antioxidants. Chemical properties of fullerene related to biological uses are discussed.

Rats subjected to extended L-tryptophan restriction during early postnatal stage exhibit anxious-depressive features and structural changes.

Serotonin transmission dysfunction has been suggested to play an important role in depression and anxiety. This study reports the results of a series of experiments in which rats were subjected to extended maize-based tortilla diets during early postnatal stages. This diet contains only approximately 20% of the L-tryptophan in normal diets of laboratory rodents. Compared with controls, experimental rats displayed a significant increase of immobility counts in the forced swimming test and exhibited anxiety-like behavior in the elevated plus maze test after 1 month of diet treatment. Low levels of serotonin contents were found in prefrontal cortex, striatum, hippocampus, and brainstem using high-performance liquid chromatography. Immunocytochemical reactions against 5-Bromo-2&vprime;-deoxyuridine revealed a significant decrease in the proliferation rate for the subgranular zone of dentate gyrus. c-Fos expression after the forced swimming test was found reduced in prefrontal cortex, dentate gyrus, CA1, and hilus of hippocampus and amygdala. Moreover, dendrite arbor atrophy and decreased spine density were evident in Golgi-Cox-impregnated CA1 pyramidal neurons. Abnormal dendrite swelling in dentate gyrus granule cells was also observed. These findings indicate an involvement of hyposerotoninergia in emotional disturbance produced by L-tryptophan restriction during critical developmental stages and suggest that neuroplasticity changes might underlie these changes.

Anxiolytic-like actions of melatonin, 5-metoxytryptophol, 5-hydroxytryptophol and benzodiazepines on a conflict procedure

Male Wistar rats (120-230 g) were used in these experiments. Some rats were deprived of water for 48 h before testing in a conflict procedure. Then, after 20 licks from a water bottle with a metal drinking tube, the animal received an electric shock (0.5 mA/500 msec). The effects of two classical anxiolytic drugs, DIAZ (1.0, 2.0 and 4.0 mg/Kg b.wt), and CDP (5.0 and 10.0 mg/Kg b.wt) were compared to those produced by MEL (0.1, 0.2, 0.5, 1.0 and 2.0 mg/Kg b.wt), 5-MTOPHOL (1.0 and 2.0 mg/Kg b.wt), 5-HTOPHOL (1.0 and 2.0 mg/Kg b.wt) and vehicle solution. Anxiolytic drugs as well as MEL produced a dose-dependent increase in the number of shocks received. The results suggest that the three pineal indoles are involved in the modulation of the stress responses. MEL showed a higher potency than the other indoles.

Glial activation in a pilocarpine rat model for epileptogenesis: A morphometric and quantitative analysis

In this work we examined the correlation between long-term glial resilience and slow epileptogenesis using the pilocarpine-insult rat model. We assessed, quantitatively and morphometrically, glial fibrillary acidic protein (GFAP) expression and cell densities in hippocampus in a dose-response manner 2, 4 and 8 weeks after the pilocarpine insult. GFAP changes were correlated with observations on microglial activation. We used a commonly applied epileptogenic pilocarpine dose (380mg/kg) and its fractions of 1/10, 1/4 and 1/2. GFAP expression evaluated at 2 weeks revealed dose-dependent cytoskeletal hypertrophy and loss of GFAP+ cell densities in hippocampus. At 4-week timepoint, recoveries of the above mentioned parameters were observed in all groups, except for the full dose group in which the astrocytic hypertrophy reached the highest level, while its density dropped to the lowest level. Strong and localized microgliosis revealed by CD11b immunoreactivity was observed in hilus in the full dose group at 2- and 4-, persisting at 8-week timepoints. Through changing pattern analysis, we conclude that the loss of astroglial resilience is likely to be a determining factor for spontaneous recurrent seizure onset.

Human and porcine neurocysticercosis: differences in the distribution and developmental stages of cysticerci

Objective  To describe and compare the clinical impacts of neurocysticercosis (NC) caused by Taenia solium in humans and pigs.

Dietary tryptophan restriction in rats triggers astrocyte cytoskeletal hypertrophy in hippocampus and amygdala

We have previously reported that dietary tryptophan (TRP) restriction in a rat crucial postnatal developmental stage induces depression-like behavior and alters dendritic spine density in CA1 pyramidal neurons and granule cells of the hippocampus. Due to astrocyte involvement in critical brain mechanisms, it seems worth to investigate possible adaptive changes in the glial population with TRP restriction. Experimental rats were fed with low TRP diet (20% of TRP level of the laboratory rat chow) from postnatal days 30-60. Antibody against glial fibrillary acidic protein (GFAP), a principal intermediate filament in astrocytes, was used to evaluate cytoskeletal hypertrophy and glial proliferation. Our results showed an increase in size and branching of GFAP-immunoreactive (IR) cells in the dorsal hippocampus and amygdala, characteristics of an astrocytic activation. No significant differences were found regarding the number of GFAP-IR cells in both regions. These results indicate that dietary TRP restriction can induce astrocytic activation, hence, provide further evidences supporting the hypothesis that serotonin may also modulate glial morphology.