Systematic expression of immediate early genes and intensive astrocyte activation induced by intrastriatal ferrous iron injection.

The potential role(s) of transitional metals such as iron have been implicated in neurodegeneration through biochemical processes, particularly oxidative stress. We injected ferrous chloride (FeCl2) and ferric chloride (FeCl3) into the striatonigral system of Sprague-Dawley rats to investigate the biological and toxic effects of ferrous iron in the central nervous system. When FeCl2 was injected into the ventral midbrain, rats showed a characteristic behavior which indicated ipsilateral dopaminergic hyperactivity. FeCl2 injection into the striatum induced a dose-dependent damage, the activation of astrocytes and recruitment of macrophage/microglia at the injected site. Interestingly, the activation of astrocytes was also observed in the anatomically remote areas such as the ipsilateral subthalamic nucleus and pars reticulata of the substantia nigra after 1 week. Expression of immediate early genes (IEGs; c-fos and NGFI-A) was observed in the cortex, thalamic nuclei, subthalamic nucleus, pars reticulata of the substantia nigra, lateral and medial geniculate bodies on the ipsilateral side from 3 to 15 h after FeCl2 injection. Pre-treatment with dimethyl sulfoxide, a hydroxyl radical scavenger, prevented FeCl2-induced expression of IEGs in the thalamic nuclei and geniculate bodies, but not in the cerebral cortex. On the other hand, the effects of FeCl3 were faint and limited on IEGs expression and tissue damage. These results suggest that ferrous iron affects the nervous system vigorously, possibly yielding free radicals such as hydroxyl radicals, and could be one of the important candidates for neurodegenerative diseases under the state in which acclimating systems for iron toxicity are disrupted.

Maltol (3-hydroxy-2-methyl-4-pyrone) toxicity in neuroblastoma cell lines and primary murine fetal hippocampal neuronal cultures.

Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminium-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocampal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2 -(4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized in situ in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. Further toxicological investigations are warranted, since maltol is found in the daily diet of humans.

Apoptosis in glial tumors as determined by in situ nonradioactive labeling of DNA breaks.

Tumor growth depends on cell division and cell death. To investigate the role of apoptosis in tumor cell death, we examined 83 cases of glial tumors using in situ nonradioactive tailing of DNA breaks. In addition, since p53 protein may participate in the regulation of apoptosis in glioblastoma, we compared the apoptosis ratio (AR) with the labeling index (LI) of p53 protein immunopositivity. The AR in glial tumor parenchyma ranged from 0 to 1.4%: mean AR +/- standard deviation was 0.4 +/- 0.4% (range, 0-1.4) for glioblastoma, 0.3 +/- 0.3% (range, 0.01-0.83) for anaplastic astrocytoma, 0.1 +/- 0.1% (range, 0-0.41) for low-grade astrocytoma, 0.006 +/- 0.008% (range, 0-0.02) for pilocytic astrocytoma, 0.2 +/- 0.2% (range, 0-0.62) for oligodendroglioma and 0.003 +/- 0.004% (range, 0-0.01) for ependymoma. ARs were significantly higher in higher-grade astrocytic tumors than in lower-grade tumors (Mann-Whitney U test: P = 0.0003), although wide variability in each group resulted in overlapping between the groups. p53 protein immunopositivity (more than 25% of nuclei) was found in 15 of 32 glioblastoma cases, while in the remaining 17 none or only a low percentage (up to 6%) of the nuclei were positive. In p53 protein-positive cases mean AR (0.51 +/- 0.47%) was not significantly higher than that in p53 protein-negative cases (0.22 +/- 0.23%; P = 0.1681).

[A characteristic blink response observed in a patient with Lance-Adams syndrome--somatosensory-evoked blink response].

We report a patient with Lance-Adams syndrome, in whom a characteristic blinking response was observed. In this patient, the reflex blinking was elicited by electrical stimulations applied not only to the supraorbital nerve but also to peripheral nerves of both upper and lower extremities. The EMG discharges responsible for the blinking response were found to consist of some components. The pathophysiological mechanism underlying the characteristic blinking response was discussed. It is speculated that increased excitabilities of the brainstem reticular formation may play a role in generating this type of blinking response, namely the somatosensory-evoked blink response.

[Pretectal syndrome caused by a plaque of multiple sclerosis].

We report a 20-year-old woman who presented with pretectal syndrome. She was well until September 12, 1991 when she noted an onset of difficulty in focusing her eyes. On neurologic examination, she showed convergence-retraction nystagmus and restriction of vertical eye movements more in the upward direction. A cranial CT scan revealed no abnormality. An oligoclonal band was detected in CSF. An MRI using Hitachi MRH-500 (0.5 T) revealed an abnormal high signal intensity lesion at the ventral area of the midbrain aqueduct, and another small lesion in the temporal white matter on the left. In addition, periventricular scattered small lesions were also visualized. Hydrocephalus, tumors and cerebrovascular disorders are common causes of pretectal syndrome, but multiple sclerosis is a rare one. Problems associated with the similar terminologies including Parinaud's syndrome, sylvian aqueduct syndrome or dorsal midbrain syndrome were discussed. According to Ranalli (1988), fibers mediating the upward gaze originate in the rostral interstitial MLF (riMLF), cross through the posterior commissure, and terminate in the contralateral oculomotor complex. On the other hand, downward gaze fibers take another route to the oculomotor complex. This may be a reason for the dissociation of the upward and downward gaze palsy, and the riMLF seems to be one of the most important structures responsible for the upward gaze.

[A 79-year-old man with rapidly progressive tetraparesis].

We report a 79-year-old man who developed progressive gait disturbance and sensory loss. He had been doing well except for hepatitis B virus hepatitis until 72 years of age when he developed angina pectoris for which aorto-coronary bypass operation was performed when he was 73-year-old (1986). In 1990, he developed pulmonary fibrosis for which prednisolone was prescribed. His liver function deteriorated, and the liver function tests suggested liver cirrhosis. He noted an onset of gait disturbance in the middle of June in 1992 when he was 79-year-old. His gait disturbance deteriorated progressively, and he developed edema and loss of sensation in his both legs. He became unable to walk unassisted in the beginning of July. He fractured his right external malleolus after falling down from a chair. He became unable to stand by himself, and he was admitted to the cardiology service of our hospital on July 18, 1992, and the neurology service was asked to see the patient on July 30 of the same month. The patient was well developed and well nourished man in no acute distress. General physical examination revealed slight jaundice, left carotid bruit, and slight pitting pretibial edema. His temperature was 37.3 degrees C. On neurologic examination, he was alert and mentally sound without dementia. He showed a slight weakness in the facial muscles bilaterally and mild dysarthria and dysphagia, however, the other cranial nerves appeared intact. He was unable to stand unassisted. The muscle tone was hypotonic, however, no focal muscle atrophy was noted, nor was observed fasciculatory twitches.(ABSTRACT TRUNCATED AT 250 WORDS)

[Superior vena cava syndrome and compression neuropathy of the right brachial plexus following cardiac pacemaker implantation].

We reported a case with the superior vena cava syndrome and compression neuropathy of the right brachial plexus after pacemaker implantation. A 27-year-old man with the second degree atrio-ventricular block had underwent pacemaker implantation via the right subclavian vein at the age of 19. Since the age of 25, he occasionally experienced paresthesia and swelling in his right arm after excessive work. These symptoms gradually resolved within a few days by rest. On June 2, 1990, he noticed swelling and paresthesia of his right face, arm and upper trunk after excessive labor. A few days later, weakness of right hand developed. On examination on June 8, the right arm was edematous, but not cyanotic. There were weakness and hypoactive muscle stretch responses in the right upper extremity with hypesthesia of all modalities in the neck, arm and upper trunk of the right side. Venous angiography showed total occlusion of the right brachiocephalic vein and superior vena cava and well-developed collateral channels. We speculate that swelling of the right upper extremity, which became overt when arterial blood supply to that limb outbalanced impaired venous drainage, finally compressed the right brachial plexus.

[Herpes simplex virus type I encephalitis with left temporal lobe lesion detected by gadolinium enhanced MRI].

A case of herpes simplex virus (type I, HSV-I) encephalitis (HSE) was reported. A 65 years old man presented acute fever and subsequently developed mental symptoms, disorientation and consciousness disturbance. HSV-I antibody titers of serum and CSF were markedly elevated, especially the elevation of IgM antibody was noticeable. MRI T1 weighted image enhanced by Gadolinium DTPA taken on the 15th day from the onset revealed a lesion in the inner side of left temporal lobe. Acyclovir therapy was administered under the diagnosis of HSE. He recovered well with the residual of moderate memory disturbance. This is a very interesting and rare case of HSE in an old patient caused by the primary infection of HSV-I. In addition, the importance of Gd enhanced MRI study to detect HSE lesion was discussed.