Hideyoshi Yokote

Transplantation of Peripheral Cholinergic Neurons into Alzheimer Model Rat Brain

The effect of transplantation of peripheral cholinergic neurons was examined in rats with a lesion of the nucleus basalis Meynert (NBM). The rats with an NBM lesion showed abnormal increase of spontaneous activity, disturbance of memory retention, and disturbance of learning acquisition. In contrast, the rats which had received transplantation of cholinergic neurons into the cerebral cortex displayed amelioration of abnormal behavior produced by the destruction of the NBM. Morphological study (acetylcholinesterase) clearly showed survival of many transplanted cholinergic cells. The present study suggests that autotransplantation of peripheral cholinergic cells may be a possible therapy for Alzheimers disease.

Stereotactic operation for brain abscess

Stereotactic management of brain abscess (stereotactic aspiration with external drainage) was performed in 14 patients. Fifteen abscesses in 14 patients were successfully aspirated by this method. After aspiration of the abscess, all patients underwent external drainage for an average of 14.5 days. No complications during aspiration or during external drainage (such as bleeding or infection, respectively) were encountered in our series. Ten out of 14 patients (71.4%) showed excellent prognosis, and 3 of 14 (21.4%) showed good outcome. Only one patient died after the operation, but this was due to lung cancer. Our operative results are quite satisfactory in comparison with operative results reported by other authors.

Effect of atrial natriuretic peptide on ischemic brain edema: changes in brain water and electrolytes.

The effects of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium, and potassium contents in ischemic brain edema were investigated. By use of a three-vessel occlusion model, ischemic brain edema was produced in the rat brain by 15 minutes of global ischemia followed by recirculation. Water content was measured by means of a drying/weighing method; sodium and potassium contents were measured by means of flame photometry. The effects of intraventricular administration of ANP were evaluated by a comparison between the groups given 2 and 5 micrograms of atriopeptin II (treated) and those given 0.9% NaCl (sham-treated). The treated groups showed significant decreases in brain water (P less than 0.02) and sodium (P less than 0.01) contents at 15 and 30 minutes after recirculation, whereas the brain potassium contents remained unaltered. Before ischemia and immediately after 15 minutes of ischemia, intraventricularly administered ANP did not significantly change the brain water, sodium, or potassium contents. There was no significant difference in the effect on the amount of brain water and sodium between the two doses (2 and 5 micrograms). These effects of ANP were thought not to be mediated by primary changes in serum osmolality and sodium and potassium concentrations, because intraventricular administration of ANP did not change them significantly. The present results reveal that, in ischemic brain edema, ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation.

The distribution of adrenergic receptors in cerebral blood vessels: an autoradiographic study

The first morphological evidence of the existence of adrenergic receptors (alpha 1, alpha 2 and beta) within the vascular walls of the central nervous system were presented using the in vitro receptor autoradiographic technique. In the rat pial arteries all three types of adrenergic receptors were demonstrated, whereas the human pial arteries failed to show significant autoradiographic grains of alpha 1 type of adrenergic receptors indicating a considerable inter-species difference in the distribution of adrenergic receptors. alpha 2 and beta receptors in human pial arteries were found not only in the arterial smooth muscle layers but also in the endothelial layers. This suggests a possibility that circulating sympathomimetic agents play some role in controlling the tone or permeability of vascular walls within the central nervous system. A distinct distribution of alpha 1 receptors in cortical layer IV where the vascular plexus was richest may suggest a relation of alpha 1 receptors and blood flow of brain parenchyma.

A possible involvement of central atrial natriuretic peptide in cerebral cortical microcirculation.

The possible involvement of atrial natriuretic peptide (ANP) in cerebral cortical microcirculation was investigated in rats by means of laser-Doppler flowmetry and immunohistochemistry. In the laser-Doppler study, local cerebral blood flow (LCBF) changes after the administration of 10(-6) to 10(-8) mol/LANP solution or vehicle (saline solution) as an intracortical injection for 5 minutes were continuously monitored throughout the 30 minutes of the study and were expressed as percentages of preinjection values represented as 0%. The administration of 10(-6) to 10(-8) mol/LANP caused a significant decrease in LCBF; the onset of LCBF responses occurred within a few minutes after the start of the injection and the decrease in LCBF reached the maximum level within 7 to 10 minutes after the completion of the administration, after which LCBF gradually recovered. In the immunohistochemical study, no specific ANP immunoreactivity was found associated with the intraparenchymal blood vessels; however, ANP-immunoreactive neurons were observed primarily in the hypothalamus and septum, in which high concentrations of ANP-containing neurons have been identified. The data from the laser-Doppler study suggest that central ANP may produce a vasoconstriction of the intraparenchymal blood vessels, regardless of whether through direct action on these vessels or through the mediation by some system in the central nervous system. Because there is no evidence for ANP-containing nerves around these vessels, the role of central ANP in the cerebral circulation must await identification of the source of perivascular ANP.

Autotransplantation of peripheral cholinergic neurons into the brains of Alzheimer model rats

SummaryCurrent hypotheses regarding Alzheimers disease implicate cholinergic function. In this study, peripheral cholinergic neurons in the vagal nodosal ganglion were transplanted into the brains of Alzheimer model rats. Eighteen Sprague-Dalwey strain rats were divided into three groups: 1) unoperated control rats, 2) rats that had undergone bilateral destruction of the nucleus basalis of Meynert (NBM) (Alzheimer model), and 3) the transplantation group in which the vagal nodosal ganglion was transplanted into the cerebral neocortex one week after the bilateral destruction of the Meynert nucleus. Seven weeks after the transplantation rat behaviour was assessed using psychological tests (spontaneous activitiy, passive avoidance response and the Hebb-Williams maze test). The Alzheimer model rats had a statistically significant increase in spontaneous activity in comparison with controls (P<0.01). The transplant rats showed some amelioration of this abnormal increase in spontaneous activity observed in the Alzheimer model rats. All of the control rats showed conditioned passive avoidance responses, while only one Alzheimer model rat retained is shocked-conditions behaviour before 24 hours (P<0.01). Three of the six transplanted rats showed complete improvement in the passive avoidance response test. In the Hebb-Williams maze test, the rats with NMB lesions made more errors than the control rats. The transplanted rats had a lower number of errors than NBM-lesioned rats but still more than the controls. Histological examination revealed many cholinergic cells in the transplanted tissue, especially in the area adjacent to the cerebral cortical surface.The present results indicate that autotransplantation of peripheral cholinergic cells ameliorates abnormal behaviour in Alzheimer model rats.

Chronic subdural hematoma after open heart surgery

Three cases of chronic subdural hematoma after open heart surgery are reported. In all cases, computed tomography scans revealed subdural accumulations of high density after cardiac surgery. The high-density areas changed into isodensity or low density with mass effect within 2 or 3 weeks. Anticoagulant (heparin) and a tearing of bridging veins after a rapid change of the brain volume by administration of mannitol can be a cause of chronic subdural hematoma. Forty-five to 60 mL of liquefied hematoma was aspirated and the outer membrane of the hematoma cavity was recognized by a trepanation.

Stereotactic hyperthermia for brain tumors.

We have developed a localized hyperthermia system using computed tomography-stereotactic surgery as malignant brain tumor therapy. In an experimental study, the temperature in the area of the cat brain within 20 mm from a radiofrequency electrode reached more than 43.7 degrees C. Intravenous administration of MCNU during hyperthermia caused a significant increase of MCNU content in the heated brain as compared with a control brain. In the clinical study, localized radiofrequent hyperthermia using stereotactic surgery was performed on 7 malignant deep-seated gliomas and 21 metastatic brain tumors. Especially, combination therapy of stereotactic hyperthermia and chemotherapy was effective treatment for gliomas less than 30 mm deep in the brain.

Autotransplantation of Parasympathetic Cholinergic Neurons into Alzheimer Model Rat Brain

Senile dementia of the Alzheimer type is a progressive disease in the aged. Based upon the hypothesis relating cholinergic function to Alzheimer’s disease1, the present study was designed to elucidate the effect of transplantation of cholinergic cells on behavioral abnormalities induced in Alzheimer-model rats. With the goal of clinical applicability, autologous vagal ganglion containing many cholinergic cells were used as a donor tissue.

Peptidergic innervation of cerebral blood vessels

Morphological and ohysiological studies concerning the innervation of peptidergic nerve fibers were carried out using inmtmohistochemistry with the PAP and hydrogen clearance method, respectively. Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactive nerve fibers were distributed within the adventitial layer of Dial arteries in the central nervous system, including the spinal cord. In cerebral pial arteries nmny VlP ~reactive fibers ran mainly in a spiral pattern almost identical to that of aoetylcholinesterase-positive fibers, suggestive of the coexistence of VlP and acetylcholine in the Dial arteries, as was reoorted in the autonomic ganglia and the cerebral cortex (H6kfelt and Lundberg 1983, Eckenstelnand Baughmsn 1984). Ultrastructural study of ~stainedmaterial demonstrated that most VIP immunostained fibers and cells were also ntmmrous in the cerebral cortex. Some of thamwere found very close to the intraparenchymal blood vessels, indicating a strong functional correlation between VIP fibers mud arterial smooth muscles. In contrast, SP ~opositive fibers around pial arteries ran in a meshwork pattern and lay relatively apart from the arterial smooth muscle layer. Neither a nerve fiber nor a cell soma immunostainedwith SP was observed within the cerebral cortex. A physiological study to investigate the regional cerebral blood flow (r-CBF) using hydrogen clearance methoddemonstrated that iontophoretically injected VIP increased the r-CBF of the rat cerebral cortex, but SP failed to show significant change in r-CBF. These results suggest an important role of VIP neurons in regulating the cerebral blood flow.