Faculty Bibliography

The effects of chlorpromazine and of some metabolites of chlorpromazine on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity were investigated. Chlorpromazine, nor1-chlorpromazine and 7-hydroxychlorpromazine reverse the apomorphine-elicited inhibition of tyrosine hydroxylase activity while nor1-chlorpromazine sulfoxide and nor2-chlorpromazine sulfoxide have no effect on this inhibition. 6-Hydroxychlorpromazine and promethazine also reverse the enzyme inhibition by apomorphine but are less potent than chlorpromazine or 7-hydroxychlorpromazine. These results show that chlorpromazine and its metabolites with antipsychotic activity are more effective in reversing the apomorphine-elicited inhibition of tyrosine hydroxylase than those metabolites which are devoid of antipsychotic activity

Endogenously depressed patients who showed an antidepressant response to the tricyclic drug imipramine continued to show sustained well being after alpha-MPT was added whereas depression returned when small doses of PCPA were added for brief periods. In one patient the antidepressant response to imipramine occurred after pre- and continued treatment with alpha-MPT. Urinary excretion levels of MHPG in one of the patients studied longitudinally did not correspond to the direction of clinical affective state but did reflect anticipated changes during alpha-MPT treatment. Implications are that serotonergic mechanisms are likely involved in the anti-depressant effects of imipramine in man

Cerebral blood flow was measured by the indicator fractionation technique in normal, acute hydrocephalic, chronic compensated hydrocephalic and craniectomized hydrocephalic cats. In the five normal cats the mean total brain blood flow was 136.1 ml/min/100 g dry weight. The six acute hydrocephalic animals demonstrated a relatively uniform 22% reduction in total blood flow. In eight chronic hydrocephalic cats CBF increased to the point where there was only an overall 7% decrease. In three hydrocephalic and craniectomized cats the CBF was reduced by 30.6%. In the acute phases there was a decrease in the number of blood vessels. Chronic compensated hydrocephalic brains had somewhat more vessels than the normal, whereas the craniectomized, massively hydrocephalic brain had a dramatic increase in both the number and caliber of blood vessels. These results clearly demonstrate that in acute obstructive hydrocephalus in cats, there is a significant decrease in CBF. The blood vessels revert to normal in shunted cats

An approach to the treatment of neonatal hydrocephalus is proposed which is intended to reduce or eliminate shunt dependency by increasing the effectiveness of remaining pathways of absorption of cerebrospinal fluid. In suitable cases, intermittent cranial compression by means of an elastic bandage or a helmet with an inflatable inner-lining may be effective. Hydrocephalus was arrested in nine of 14 children treated with this method, eight of whom have developed normally. When cranial compression is contra-indicated or not successful, the preferred method of treatment is an 'on-off' type of valve which is used intermittently to drain a fixed volume of cerebrospinal fluid. Of 18 children who had such shunts inserted, 10 have become totally independent of their shunts and their hydrocephalus has become compensated. All are of normal intelligence. Subtemporal craniectomy was performed on seven shunt-dependent children with recurrent catheter obstruction. Four have been followed for six months and three for two years and in no case has there been further malfunction of the proximal catheter

The purpose of this study was to ascertain the sequence of events and the cellular constituents involved in reconstituting the cortical mantle after ventricular shunting. The subjects were severely hydrocephalic adult cats. After insertion of a shunt, the ventricular system rapidly returned to normal size and there was gross reconstitution of the cortical mantle. However, there still remained in the cortical mantle many of the histological changes seen before insertion of the shunt. The effect of hydrocephalus is mainly upon axons in the periventricular white matter. The axons become stretched and finally disrupted, resulting in disintegration of the surrounding myelin. In the absence of axons, remyelination cannot take place. It would seem, therefore, that prompt reversal of hydrocephalus is necessary in order to preserve the anatomical and functional integrity of the brain.

The effects of kaolin-induced hydrocephalus on regional blood-flow and water content of cat brain and spinal cord were measured. The role of the central canal of the spinal cord as an alternative pathway for cerebrospinal fluid in experimental hydrocephalus was also studied by positive contrast ventriculography. In comparison with normal cats, blood-flow in the cerebrum, cerebellum and brain stem of cats with acute hydrocephalus was reduced by more than 20 per cent: in those with chronic hydrocephalus it was reduced by only 12 per cent. There was an absolute increase of 1-5 per cent in water content of the brain in cats with acute hydrocephalus. Water content in the spinal cord was increased by 6 per cent in cats with acute hydrocephalus and by 8 per cent in those with chronic hydrocephalus. When the increased water-content was taken into account, hydrocephalus caused no significant change in blood-flow in the cervical, thoracic or lumbar spinal cord. Contrast material perfused through the ventricles of hydrocephalic cats flowed directly into the enlarged central canal of the spinal cord. Kaolin-induced arachnoiditis completely obstructed communication between the ventricles and the cranial subarachnoid space. The contrast material in the central canal communicated both with the cavities extending into the dorsal columns and with the spinal subarachnoid space. When kaolin was injected directly into the spinal subarachnoid space there was an increase in spinal water-content, without an enlarged central canal. These results suggest that in addition to kaolin-induced arachnoiditis, increased intraluminal pressure is necessary to enlarge the central canal.