Summary:We evaluated neuronal and histological changes of thalamic neurons 1, 4, 7, and 14 days after middle cerebral artery (MCA) occlusion in rats. After the somatosensory evoked potentials (SEPs) were measured from the cerebral cortex, the thalamic relay neuronal ac tivities were recorded with a glass microelectrode follow ing repetitive electrical stimulation of the contralateral forepaw at frequencies ranging from 1 to 50 Hz. In -95% of the occluded rats, the ipsilateral somatosensory cortex and/or the subcortical somatosensory pathway developed infarct, resulting in SEP loss. We evaluated unit data from rats with abolished SEPs. The average firing rate of the nucleus ventralis posterolateralis (VPL) neurons in response to 25 stimulations at 30 Hz was significantly reduced to 0.1 spike/stimulus 1 day after MCA occlusion.After the occurrence of a localized brain lesion, neuronal structures remote from the primary lesion develop functional and/or histological changes through the neuronal pathway. The thalamocortical and the corticothalamic pathway closely connects the cerebral cortex and the ipsilateral thalamus. Cortical infarct results in progressive degeneration in the ipsilateral thalamus in humans and rats

Electromyographic studies of the monosynaptic reflex in 70 Parkinsonian patients and 12 normal subjects show four types of abnormal facilitation and recovery curves in the Parkinsonian group, types that correspond to variations in the clinical syndrome; Cryosurgical lesions in the, ventro-lateral and ventro-postero-lateral nuclei of the thalamus restore essentially normal curves.

Regional cerebral blood flow (CBF) in eight patients in a persistent vegetative state was measured and compared with that in five healthy volunteers. The patients were classified into three groups: Group 1 (locked-in syndrome) consisted of a single patient, Group 2 (typical vegetative state) of five patients, and Group 3 (prolonged coma) of two patients. CBF was measured early after onset by single photon emission computed tomography with ^{123I-N-isopropyl-p-iodo-amphetamine and/or 99mTc-hexamethyl propyleneamine oxime. The regions of interest (ROIs) were the bilateral frontal, temporal, parietal, occipital, and cerebellar areas and basal ganglia. The values obtained in these areas were averaged, and the ratio for each ROI [(the value in the ROI/the mean value) x 100] was calculated. "Hyper frontal distribution" of CBF was found to be rare in both the normal condition and the vegetative state. Higher CBF values were noted in the left than in the right frontal area in four of the five volun teers but in only four of the eight patients. CBF distribution in the frontal lobe was characteristic for each group: Group 1 showed high CBF bilaterally, although the elevation was statistically sig nificant only on the right side, and Group 3 exhibited significantly low values. In Group 2, CBF was variable but, for the most part, within normal limits. Awareness was closely correlated with frontal lobe function and alteration of CBF in the frontal region.}

The effect of dopamine during barbiturate therapy was investigated in 29 cats including 5 sham-operated cats. According to Kiersey's classification of electro-encephalographic patterns, physiological variables, cerebral metabolic rates for oxygen and glucose, cerebral blood flow (CBF), and intracranial pressure (ICP), etc. were evaluated in each electro-encephalographic pattern. Oxygen-glucose index was calculated and used as an indicator for aerobic or anaerobic metabolism of glucose. Group 1 (12 cats), to which only thiamylal was administered, maintained aerobic glycolysis due to a parallel reduction of cerebral metabolic rates for oxygen and glucose (about half of the initial value at Kiersey's fifth pattern) in spite of reduction of CBF and mean arterial blood pressure (MABP). Group 2 (12 cats), to which dopamine was administered in addition to thiamylal due to a reduction of MABP, showed anaerobic glycolysis though MABP and CBF were maintained. These findings are ascribed to an increase of cerebral metabolic rate for glucose up to 130% of the initial value though cerebral metabolic rate for oxygen decreased down to half of the initial value: The beneficial effect of barbiturate on cerebral metabolism was reduced by use of dopamine. ICP was reduced in both groups. Our result indicates that administration of extracellular fluid may be preferable for treatment of hypotension during barbiturate therapy than dopamine medication.

For patients with nonresectable glioblastoma (GB) or recurrent GB, we have recently been using an interstitial chemotherapy with biodegradable polylactic acid pellets containing nimustine chloride (ACNU), in combination with superselective arterial ACNU injection, routine irradiation and chemotherapy. The ACNU pellets are prepared by mixing polylactic acid powder and ACNU, and then melting the mixture at low temperature and moulding it into a thin pellet. Pharmacological anticancer activity was experimentally demonstrated by the finding that a region of suppression was present surrounding an ACNU pellet placed in a B6 melanoma cell culture disc, but that no such suppression was present around a control pellet. In order to determine the spatial and temporal distribution of ACNU, a small pellet (ACNU: 0.6 mg) was implanted in the frontal lobe of rats. ACNU concentration determined by HPLC was 61.0 µ/g brain tissue on day 1. 22.5 on day 3, and 5.5 on day 7; small amounts of ACNU were in fact released for at least 4 weeks after implantation. This pellet was used for the clinical treatment of 11 GB patients. Four patients had several pieces of pellets implanted immediately after CT-guided stereotactic biopsy, and the other 7 had pellets placed in residual tumor after partial removal at craniotomy. No ACNU was detectable in serum. CT studies obtained at subsequent appropriate intervals disclosed gas formation around the pellets, a slight increase in edema, and necrosis or decrease in CT enhancement of tumor beginning around day 12 after implantation. Bone marrow suppression did not occur, since ACNU was administered interstitially and in the range of 50–200 mg (average: 126 mg) per patient. Most patients underwent other modalities of antitumor treatment 2 or 3 weeks after implantation. Although the median survival time (MST) for all patients was 21 weeks, and thus not favorable, about half of those treated were old, and half of the tumors treated were located in midline structures. However, the MST for hemispheric GB patients was more favorable than that for midline tumors (47 vs. 17 weeks). There was no significant difference in survival time between the group of patients with stereotactic implantation and the group subjected to craniotomy. In conclusion, a large dose of ACNU can be implanted locally without systemic side effects using biodegradable, slowly releasing pellets. This type of treatment is thus an additional option in the treatment of malignant brain tumors.