[A case of progressive multifocal leukoencephalopathy with alcoholic liver dysfunction].

Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection by JC virus and presents with progressive demyelinating lesions in the central nervous system. A 59-year-old man with a history of alcoholic liver dysfunction presented with progressive weakness of his left leg over a period of one month. MRI showed multiple white matter lesions that were of low intensity on the T1 image and high intensity on the T2 image, heterogeneously high intensity on the diffusion image, and were not enhanced with contrast media. The patient underwent open biopsy of the right parietal lesion. The histological findings were the demyelination and the enlargement of nuclei of oligodendrocytes. Electron microscopic examination showed numerous viral particles in the nuclei of the oligodendrocytes. Infection by JC virus in the central nervous system was diagnosed with the polymerase chain reaction (PCR) products sampled from the cerebrospinal fluid. The incidence of PML has significantly increased in immunosuppressive patients, such as AIDS (acquired immunodeficiency syndrome). We presented the first case of PML in an immune-compromised state with alcoholic liver dysfunction.

[Intracranial internal carotid artery aneurysm associated with extracranial occlusion of the ipsilateral internal carotid artery in a patient with polycystic kidney disease].

We report a rare case with polycystic kidney disease (PKD) having an intracranial internal carotid artery aneurysm associated with extracranial occlusion of the ipsilateral internal carotid artery. A 55-year-old man with chronic renal failure due to PKD presented with headache. CT scan and MRI showed no abnormal findings. MRA showed cervical occlusion of the right internal carotid artery and an ipsilateral intracranial carotid aneurysm. At surgery, the saccular aneurysm protruded anterolaterally at the C2 portion of the right internal carotid and was clipped. Hemodynamic stress of the blood flow through the posterior communicating artery and the fragility of arteries because of PKD were considered to be two main causes of aneurysmal formation in this case.

[Aneurysms at the early branch of middle cerebral artery].

The cortical arteries arising from the proximal (Ml) segment of the middle cerebral artery (MCA) are called "early branches". We retrospectively analyzed clinical features in 10 patients with aneurysms located at the early branches of MCA. The incidence of these aneurysms was 9.5% among 95 MCA aneurysms. Patients consisted of 4 males and 6 females. Ages were 33-77 years old (average of 54.4). Four patients presented with subarachnoid hemorrhage (2 of them had intracerebral hematoma). The aneurysms were classified into 2 groups, the group of the early frontal branch (EFB: 7 cases) and the early temporal branch (ETB: 3 cases). All aneurysms were smaller than 6mm in diameter. The surgical treatment was performed through the pterional approach. Poor outcome occurred in 3 ruptured aneurysms of EFB (MD 1, SD 1, and D 1). At surgery, it is necessary to produce the working space by dissecting sylvian fissure sufficiently and to prevent ischemic complication by avoiding injury of the lenticulostriate arteries (LSA).

[High b-value diffusion-weighted imaging of acute brain infarction].

High b-value diffusion-weighted (DW) imaging obtained with a b-value of 2,000 s/mm2 offers theoretical advantages over DW imaging obtained with a b-value of 1,000 s/mm2 for detection of acute brain infarction. The purpose of this study was to determine whether high b-value DW images (b=2,000) are better than b=1,000 images for detection of diffusion change in patients with acute brain infarction. We compared diffusion-weighted (DW) images obtained with a b-value of 1,000 s/mm2 with those obtained with a b-value of 2,000 s/mm2 in 84 patients with small lesions (brain stem infarction, lacuna infarction) examined within 24 hours of clinical onset. Qualitative analysis was performed concerning lesion conspicuity. In quantitative analysis, contrast ratios (CR) were measured and findings of b=1,000 and b=2,000 images were compared. False-negative rate of b=1,000 and b=2,000 images were 23.8% and 3.6%, respectively, relative to the presense or absense of infarction on the follow-up MR or CT images. On qualitative analysis, lesions were more conspicuous on b=2,000 images. On quantitative analysis, as the b-value increased, mean CR increased. DW images aquired with a b-value of 2,000 s/mm2 were better than DW images aquired with a b-value of 1,000 s/mm2 for detection of diffusion change in patients with acute brain infarction.

The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model.

Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects on dopaminergic (DA) neurons. In this study, we investigated whether the effects of VEGF were dose-dependent or not. First, VEGF was shown to be neuroprotective on 6-hydroxydopamine (6-OHDA)-treated murine DA neurons in vitro, although the 1 ng/ml of VEGF displayed more neuroprotective effects than 100 ng/ml. Furthermore, using 2 sizes of capsules (small/large) with different secreting quantities, 6-OHDA-treated rats receiving the small capsule filled with VEGF-secreting cells (BHK-VEGF) into the striatum showed a significant decrease in amphetamine-induced rotational behavior in number and a significant preservation of TH-positive fibers compared to those receiving the large BHK-VEGF capsule as well as those receiving BHK-Control capsule. Rats receiving the large BHK-VEGF capsule showed much more glial proliferation, angiogenesis, and brain edema around the capsule than those with the small one. High-dose administration of VEGF might cause poor circulation related to brain edema, although low-dose administration of VEGF displays neuroprotective effects on DA neurons. Our results demonstrate the importance of administration dose of VEGF, suggesting that low-dose administration of VEGF might be desirable for Parkinson's disease.

Characteristics of hypothermic preconditioning influencing the induction of delayed ischemic tolerance.

OBJECT: A brief period of hypothermia has recently been shown to induce delayed tolerance to ischemic brain injury. This form of tolerance is initiated several hours after hypothermic preconditioning (HPC) and persists for a few days. Hypothermia-induced tolerance could provide a means for limiting cellular injury during predictable periods of ischemia, such as those that occur during many surgical procedures. The purpose of this study was to characterize the parameters of HPC that regulate the induction of delayed tolerance. METHODS: The general design of the experiments was to perform HPC or a sham procedure on adult Sprague-Dawley rats. Twenty-four hours later, the animals were subjected to a transient period of ischemia induced by a 1-hour period of three-vessel occlusion. Infarct volume was assessed 24 hours postischemia. In the first series of experiments, the depth of global (that is, whole-body) HPC was set at 25.5, 28.5, or 31.5 degrees C, and the duration of HPC was fixed at 20 minutes. In the second series of experiments, the duration of global HPC was set at 20, 60, 120, or 180 minutes, and the depth of HPC was set at 33 or 34.5 degrees C. In the third series of experiments, focal HPC was administered by selectively cooling the head to achieve a cortical temperature of 28.5 or 31.5 degrees C for 20 minutes, with the duration of HPC fixed at 20 minutes. The magnitude of tolerance induced by HPC was dependent on the depth and duration of the hypothermic stimulus. The parameters of hypothermia that are capable of inducing tolerance are similar to, or less severe than, those already in clinical use during intraoperative procedures. Focal cooling was as effective as global cooling for eliciting tolerance, indicating that it is possible to establish tolerance while limiting the potential complications of systemic hypothermia. CONCLUSIONS: The results of these experiments indicate that HPC may provide an effective and safe means for limiting cellular injury resulting from predictable periods of central nervous system ischemia.

Effects of hypothermia and rewarming on evoked potentials during transient focal cerebral ischemia in cats.

We examined the effects of mild to moderate hypothermia and the influence of rewarming on electrophysiological function using somatosensory evoked potentials (SEPs) in transient focal ischemia in the brain. Nineteen cats underwent 60 min of left middle cerebral artery occlusion under normothermic (36 degrees-37 degrees C, n = 6) or hypothermic (30 degrees -31 degrees C, n = 13) conditions followed by 300 min of reperfusion with slow (120 min, n = 6) or rapid (30 min, n = 7) rewarming. Whole-body hypothermia was induced during ischemia and the first 180 min of reperfusion. SEPs and regional cerebral blood flow were measured before and during ischemia and during reperfusion. The specific gravity of gray and white matter was examined as the indicator of edema. During rewarming, SEP amplitudes recovered gradually. After rewarming, SEPs in the normothermic and rapid rewarming groups remained depressed (20%-40% of pre-occlusion values); however, recovery of SEPs was significantly enhanced in the slow rewarming group (p < 0.05). Hypothermia followed by slow rewarming reduced edema in gray and white matter. Rapid rewarming did not reduce edema in the white matter. The recovery of SEPs correlated with the extent of brain edema in transient focal ischemia. Rapid rewarming reduced the protective effect of hypothermia.

A new method of inducing selective brain hypothermia with saline perfusion into the subdural space: effects on transient cerebral ischemia in cats.

In this study, we tested brain surface cooling as a new method of inducing selective brain hypothermia, and evaluated its effects on focal cerebral ischemia using a cat model of transient middle cerebral artery (MCA) occlusion. Cats underwent 1 h of MCA occlusion followed by 5 h of reperfusion. Brain surface cooling was induced for 4 h during and after MCA occlusion in the hypothermia group, but not in the normothermia group. Brain surface cooling was performed using saline perfusion into the subdural space. Rectal temperature, brain surface temperature, and deep brain temperature were monitored, and regional cerebral blood flow (rCBF) and somatosensory evoked potential (SEP) were serially measured. After 5 h of reperfusion, water content was also measured. Although the rectal temperature was maintained at about 37 degrees C, the brain surface temperature decreased rapidly to 33 degrees C and was maintained at that temperature. For 3 h following reperfusion, the rCBF was lower in the hypothermia group than in the normothermia group. At 4 and 5 h after reperfusion, the recovery of SEP amplitude was significantly more enhanced in the hypothermia group than in the normothermia group. In the gray matter, the water content was significantly more diminished in the hypothermia group than in the normothermia group. These results demonstrate that our method is useful for protecting the ischemic brain from a transient MCA occlusion. This method may be adapted for neurological surgery.

Hypothermic preconditioning induces rapid tolerance to focal ischemic injury in the rat.

Stressful, preconditioning stimuli can elicit rapid and delayed forms of tolerance to ischemic injury. The identification and characterization of preconditioning stimuli that are effective, but relatively benign, could enhance the clinical applicability of induced tolerance. This study examines the efficacy of brief hypothermia as a preconditioning stimulus for inducing rapid tolerance. Rats were administered hypothermic preconditioning or sham preconditioning and after an interval of 20-120 min were subjected to transient focal ischemia using a three-vessel occlusion model. The volume of cerebral infarction was measured 24 h or 7 days after ischemia. In other experiments, the depth or duration of the hypothermic stimulus was manipulated, or a protein synthesis inhibitor (anisomycin) was administered. Twenty minutes of hypothermia delivered 20 or 60 (but not 120) min prior to ischemia significantly reduces cerebral infarction. The magnitude of protection is enhanced with deeper levels of hypothermia, but is not affected by increasing the duration of the hypothermic stimulus. Treatment with a protein synthesis inhibitor does not block the induction of rapid tolerance. Hypothermic preconditioning elicits a rapid form of tolerance to focal ischemic injury. Unlike delayed tolerance induced by hypothermia, rapid tolerance is not dependent on either de novo protein synthesis or the duration of the preconditioning stimulus. These findings suggest that the mechanisms underlying rapid and delayed tolerance induced by hypothermia differ fundamentally. Brief hypothermia could provide a rapid means of inducing transient tissue protection in the context of predictable ischemic events.

Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide.

In glutamate-mediated excitatory neuronal cell death, immunosuppressants (FK506, Cys-A) are powerful agents that protect neurons from apoptosis. Immunosuppressants inhibit two types of enzyme, calcium/calmodulin-dependent protein phosphatase (calcineurin: CaN), and peptidyl-prolyl cis-trans-isomerase (PPIase) activity such as the FKBP family. In this study, we used a protein transduction approach to determine the functional role of CaN and to produce a potential therapeutic agent for glutamate-mediated neuronal cell death. We created a novel cell-permeable CaN autoinhibitory peptide using the 11 arginine protein transduction domain. This peptide was highly efficient at transducing into primary culture neurons, potently inhibited CaN phosphatase activities, and inhibited glutamate-mediated neuronal cell death. These results showed that CaN plays an important role in excitatory neuronal cell death and cell-permeable CaN autoinhibitory peptide could be a new drug to protect neurons from excitatory neuronal death.