Background and Purpose-Stroke triggers increased progenitor proliferation in the subventricular zone (SVZ) and the generation of medium spiny neurons in the damaged striatum of rodents. We explored whether intrastriatal infusion of glial cell line-derived neurotrophic factor (GDNF) promotes neurogenesis after stroke. Methods-Adult rats were subjected to 2-hour middle cerebral artery occlusion (MCAO). GDNF was infused into the ischemic striatum either during the first week after MCAO, with the animals being killed directly thereafter, or during the third and fourth weeks, with the rats being killed 1 week later. New cells were labeled with 5Ј-bromo-2Јdeoxyuridine (BrdU) on day 7 or during the second week, respectively. Neurogenesis was assessed immunocytochemically with antibodies against BrdU and neuronal, glial, or progenitor markers. GDNF receptor expression was analyzed in SVZ tissue and neurospheres by reverse transcription-polymerase chain reaction and immunocytochemistry. Results-GDNF infusion increased cell proliferation in the ipsilateral SVZ and the recruitment of new neuroblasts into the striatum after MCAO and improved survival of new mature neurons. The GDNF receptor GFR␣1 was upregulated in the SVZ 1 week after MCAO and was coexpressed with markers of dividing progenitor cells. Conclusions-Intrastriatal infusion of GDNF in the postischemic period promotes several steps of striatal neurogenesis after stroke, partly through direct action on SVZ progenitors. Because delivery of GDNF has biological effects in the human brain, our data suggest that administration of this factor may promote neuroregenerative responses in stroke patients.

The occurrence of PIH may be related to the region of epileptic focus and the region of spread of epileptic discharges.

We investigated post-ictal headaches (PIH) using a questionnaire to ascertain their characteristics and compare them among different types of epilepsy. The subjects consisted of 34 patients with occipital lobe epilepsy (OLE) and 75 patients with temporal lobe epilepsy (TLE). PIH occurred in 62% of OLE and 23% of TLE (P < 0.05). The quality of pain in PIH was 'steady' in 71% of OLE and 29% of TLE (P < 0.05) as opposed to 'pounding'. Other factors, such as frequency, severity, duration, and accompanying symptoms showed no significant differences. We found very few patients with migraine-like headaches. Analyses of clinical factors, such as age at onset, duration of epilepsy, seizure frequency, family history of headache, and interictal headache did not reveal any relationship to PIH, although generalized tonic-clonic seizures are associated with PIH in TLE (P < 0.05). These results suggest that the nature of PIH may be different between OLE and TLE, and that the region of epileptic focus or spreading area of epileptic discharge may have a close relation to the induction of PIH. An association with migraine, which has been reported previously, was unclear in our study.

Summary:Hepatic veno-occlusive disease (VOD) is one of the most serious complications in patients receiving stem cell transplantation (SCT). However, the cause of VOD remained to be elucidated. Vascular endothelial growth factor (VEGF) has been reported to have various physiological effects including neovascularization and acceleration of vasopermeability. Because we postulated that VEGF could be one of the causative factors in VOD after SCT, serum VEGF levels were measured by ELISA in 50 patients receiving SCT. Six of the patients showed typical manifestations of VOD and four of them died due to VOD. The mean maximum serum VEGF level in the six patients with VOD was markedly increased compared to that in the patients without VOD (P Ͻ 0.001) and in normal controls (P Ͻ 0.001). Moreover, the mean maximum serum VEGF level in patients with VOD before conditioning chemoradiotherapy for SCT was also high compared to patients without VOD (P = 0.0012) in the same period. Similarly, serum VEGF levels were significantly higher in patients whose plasma protein C activities decreased below 40% (P Ͻ 0.001). During the clinical course of VOD after SCT, the increase of serum VEGF synchronized fairly well with the development of VOD. Since VEGF causes the expression of tissue factor on circulating monocyte/ macrophages and results in hypercoagulability, our observation suggests that in the patients with VOD who showed high serum VEGF it might account for the development of VOD. Furthermore, this observation may indicate a novel therapeutic strategy for prevention of VOD. Bone Marrow Transplantation (2001) 27, 1173-1180.

The amount of slow wave sleep (SWS) declines with increasing age 1,2 and it is well known that gender difference on sleep parameters have been noted in the middle aged and elderly. 3,4 The purpose of this study is to investigate gender effects on slow wave activity in middle aged and elderly subjects by spectral analysis. SUBJECTS AND METHODSEight healthy male subjects (61.50 ± 4.66 years) and eight female subjects (62.38 ± 6.65 years) participated in this study. None of the participants had had a significant medical history and during the study were free of medication. The subjects were asked to avoid sleep during the day and sleep electroencephalograms were recorded for three consecutive nights at their homes using an ambulatory monitoring system to maintain their daily sleep conditions. Third-night EEG were visually scored by a 20-s epoch according to the criteria of Rechtschaffen and Kales. The EEG (C3-A2) was digitized at a sampling rate of 125 Hz (the sampling period was 8 ms). Power spectra were calculated by FFT over 1024 data points with a cosine bell window. The spectral power through nocturnal sleep and the mean spectral power per 30 s were obtained for two frequency bands (0.5-2 Hz and 2-4 Hz). For statistical analysis, the spectral power was normalized by a logarithmic transformation and the Mann-Whitney U test was used to compare spectral power between genders. Figure 1 shows two hypnograms for both male and female subjects. The sleep continuity of a male subject aged 61 years was maintained, while a female subject aged 72 years showed long awakenings in the latter part of sleep. The length of SWS was shown to be longer in the female than the male. There were no significant gender differences in visually scored EEG parameters: time in bed, sleep period time, total sleep time, sleep efficiency, number of awakenings, sleep latency, REM latency and percentages of stage W, 1, 2, REM. However, females showed a higher percentage of stage 3 + 4 as compared with males (mean % ± SD, Psychiatry and Clinical Neurosciences (1999) RESULTS AbstractSleep EEG of eight healthy males and eight females aged 54-72 years were recorded at their homes. The electroencephalograms were visually scored and analyzed by spectral analysis using the FFT method. There were no significant differences in sleep parameters except for a higher percentage of stage 3 + 4 in females. The spectral power of the delta band EEG was classified into two frequencies: 0.5-2 Hz and 2-4 Hz. The total amount of the delta band spectral power through the night was significantly larger in females. Periodic fluctuation of delta band power was observed in females along with non-rapid eye movement-rapid eye movement cycles.

The effects of lunchtime bright light exposure in patients of a geriatric hospital were investigated. Ten inpatients (six women and four men; mean age ± SD: 81.2 ± 8.8 years) with sleep disturbances were studied for 9 weeks. Nurses performed daily ratings for sleep-wakefulness disturbances. Approximately 8000 lx bright light exposure was performed for 3 weeks in the light therapy room. Before and after exposure, ocular function was evaluated. Clinical ratings of sleepwakefulness improved in eight patients. The score of difficulty in falling asleep and drowsiness in the morning declined during the light exposure. The score of drowsiness in the afternoon decreased during the post-light exposure. Post-exposure ocular disturbances were not found.

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Eight healthy elderly women aged 56-72 years (mean age: 67.4 years) participated in this study. They were exposed to moderately bright light (1000 lux) for 1 h in the morning every 6 days in their homes. Moderately bright light improved self evaluations for alertness, mood, motivation, happiness, refreshment, concentration and appetite after the second exposure to the light. Sleep maintenance, anxiety and integrated sleep feeling also improved after the fourth exposure to the light. The phase of rectal temperature rhythm did not change in a moderately bright light condition. These results suggest that bright light influences sleep quality and self evaluations without changing the biological rhythm phase.