Acutely, STN stimulation improved rotation symmetry in rats with moderate SNc degeneration. When STN stimulation had been applied for the preceding 2 weeks, motor function was better and SNc neural degeneration was significantly milder. Subthalamic nucleus stimulation thus appears to protect dopaminergic neurons in this hemiparkinsonian model, in addition to improving motor function in these animals.

Object. Gamma knife surgery (GKS) has been a safe and effective treatment for vestibular schwannomas in both the short and long term, although less is known about long-term outcomes in the past 10 years. The aim of this study was to clarify long-term outcomes in patients with vestibular schwannomas treated using GKS based on techniques in place in the early 1990s. Methods. Eighty patients harboring a vestibular schwannoma (excluding neurofibromatosis Type 2) were treated using GKS between May 1991 and December 1993. Among these, 73 patients were assessed; seven were lost to follow up. The median duration of follow up was 135 months. The mean patient age at the time of GKS was 56 years old. The mean tumor volume was 6.3 cm3, and the mean maximal and marginal radiation doses applied to the tumor were 28.4 and 14.6 Gy, respectively. Follow-up magnetic resonance images were obtained in 71 patients. Forty-eight patients demonstrated partial tumor remission, 14 had tumors that remained stable, and nine demonstrated tumor enlargement or radiation-induced edema requiring resection. Patients with larger tumors did not fare as well as those with smaller lesions. The actuarial 10-year progression-free survival rate was 87% overall, and 93% in patients with tumor volumes less than 10 cm3. No patient experienced malignant transformation. Conclusions. Gamma knife surgery remained an effective treatment for vestibular schwannomas for longer than 10 years. Although treatment failures usually occurred within 3 years after GKS, it is necessary to continue follow up in patients to reveal delayed tumor recurrence.

Object. In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor, is widely administered to prevent vasospasm in patients after subarachnoid hemorrhage. The effects of fasudil on experimental spinal cord injury (SCI) were investigated and compared with those obtained using methylprednisolone. Methods. Spinal cord contusion was induced in rats by applying an aneurysm clip extradurally to the spinal cord at T-3 for 1 minute. After injury three groups of rats were treated with intravenously administered saline (control), intraperitoneally administered fasudil (10 mg/kg), or intravenously administered methylprednisolone (four 30 mg/kg injections). Neurological recovery was evaluated periodically over 1 month by using a modified combined behavioral scale and histopathological examination. Leukocyte infiltration near the injury site was evaluated by measuring myeloperoxidase (MPO) activity at 24 hours. Spinal cord blood flow was measured at intervals up to 3 hours after injury by using laser Doppler flowmetry. In rats in the fasudil-treated group significant improvement in modified combined behavioral score was demonstrated at each time point, whereas in the methylprednisolone-treated rats no beneficial effects were shown. In the fasudil-treated group, reduction of traumatic spinal cord damage was evident histologically in the caudal portion of the injured areas, and tissue MPO activity in tissue samples was reduced. Spinal cord blood flow was not significantly different between fasudiltreated and control group rats. Conclusions. Fasudil hydrochloride showed promise of effectiveness in promoting neurological recovery after traumatic SCI. Possible mechanisms of this effect include protein kinase inhibition and decreased infiltration by neutrophils.

In the course of our screening program for a new Ca 2ϩ -signal transduction inhibitor using the hypersensitive mutant strain of Saccharomyces cerevisiae (zds1D erg3D pdr1D pdr3D ), new eremophilane sesquiterpenoid compounds eremoxylarins A and B were found to restore the growth inhibition caused by the hyperactivated Ca 2ϩ -signal. These compounds showed lethal activity against the mpk1D strain, specifically, compared to the cnb1D strain, and ion-sensitive activity against the wild-type strain in the presence of LiCl, indicating that their molecular target might be the calcineurin pathway. They inhibited calcineurin directly without immunophilins at IC 50 ϭ2.7 and 1.4 m M with competitive inhibition in vitro. The eremophilane sesquiterpenoid structure in eremoxylarins could be a good leading compound for immunosuppressants and anti-allergy drugs.

This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.