No abstract

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.

We tested the hypothesis that conduction of vasomotor responses occurs in cannulated and isolated rat cerebral penetrating arterioles. Both at the site of stimulation (local) and 500-650 microns distant from it, we observed the diameter responses and time courses thereof to pressure-ejected vasoactive stimuli. ATP locally caused an initial constriction (response onset at 0.3 s, average diameter 85% of control at 450-ms pulse with a maximum at 1.6 s after stimulation) followed by a secondary dilation (111% at 7 s). Conducted vasodilation of 111% was observed over a distance of 520 microns. Prostaglandin F2 alpha (PGF2 alpha) constricted the vessels locally (80%) and caused conducted vasodilation (110%). For both ATP and PGF2 alpha the local constriction occurred simultaneously to the conducted vasodilation. Adenosine dilated the vessels (123%) but produced only inconsistent conducted vasodilation. Hydrogen ions initially constricted the vessels (88%) and then dilated them to 113%. Thus, although ATP and PGF2 alpha are strong promoters of conduction, adenosine and hydrogen ions are not. Paradoxically, ATP and PGF2 alpha caused conducted vasodilation even though the initial local response was a vasoconstriction, indicating that in cerebral arterioles conduction may be mediated through endothelial cell mechanisms rather than through smooth muscle cell communication.

These findings suggested that beta amyloid peptide was derived from the processing of APP produced in the same reactive astrocytes and the production of the peptide stopped within 60 days after the ischemic stress.

Transfer of interferon beta gene via cationic liposomes has been found to induce regression of experimental glioma. We performed a pilot clinical trial of safety and effectiveness of this interferon beta gene therapy in five patients with malignant glioma (glioblastoma multiforme or anaplastic astrocytoma). Transgene expression and antitumor activity were detected in four patients. Two patients showed a partial response (>50% tumor reduction) and two others had stable disease 10 weeks after beginning therapy. One patient could not be evaluated because of previous treatment with gamma-knife therapy. This study suggests the feasibility and safety of interferon beta gene therapy, which may become an important treatment option for patients with malignant glioma.