Prolongation of dioestrus in rats with diencephalic and mesencephalic lesions

Summary Diencephalic and mesencephalic lesions in albino rats elicited a disturbance of the vaginal oestrous cycle characterized by pseudopregnancy-like prolongation of dioestrus; occasionally decidual responses could be elicited by uterine traumatization. Oestrogen administration on the day before traumatization failed to enhance significantly the frequency of decidual responses in rats with diencephalic lesions, but succeeded in doing so in rats with mesencephalic lesions. It is assumed that the lesions destroy partially the mesencephalo-hypothalamic afferent system containing nerve fibres stimulating the hypothalamic cells producing the luteotrophin (prolactin) inhibiting factor.     

Preoptic-hypothalamic periventricular lesions: impairment of thirst-motivated behavior

To assess the effect of anteroventral third ventricle (AV3V) lesions on thirst-motivated behavior in the rat, the intake of quinine hydrochloride (QHCl) solutions and of QHCl-adulterated food was evaluated. Two-bottle choice tests were also administered to determine if lesions altered the rejection threshold for QHCl solutions. AV3V ablation significantly reduced QHCl solution intake in a one-bottle test, but did not alter the two-bottle preference relationships. Ingestion of QHCl-adulterated food was slightly reduced only if the animals had no prior experience with the taste of QHCl. These findings suggest that AV3V ablation produces deficits in thirst-motivated behavior, and that AV3V periventricular tissue contains elements necessary for the elaboration of normal thirst.     

Central role of microglia in neonatal excitotoxic lesions of the murine periventricular white matter

Periventricular leukomalacia (PVL) is the main cause of neurologic handicap in pre-term infants. The understanding of cellular and molecular mechanisms leading to white matter damage is critical for development of innovative therapeutic strategies for PVL.The pathogenesis of PVL remains unclear but possibly involves glutamate excitotoxicity as an important molecular pathway. We previously described a neonatal mouse model of excitotoxic white matter lesion mimicking human PVL. In the present study, we used this experimental tool to investigate the cellular populations and the glutamate receptor subtypes involved in excitotoxic white matter lesions. Combined immunohistochemical, electron microscopic, and cell death detection data revealed that microglial activation and astrocytic death were the primary responses of white matter to excitotoxic insult. In vitro experiments suggested that microglia activated by ibotenate released soluble factors that kill astrocytes. The use of selective agonists and antagonists of glutamate receptors revealed that N-methyl-D-aspartate (NMDA) receptor activation was essential and sufficient to produce cystic white matter lesions. NMDA receptor immunohistochemistry labeled microglial cells in the neonatal periventricular white matter. The developing white matter displayed a window of sensitivity to excitotoxic damage that was paralleled by the transient presence of NMDA receptor-expressing white matter cells. Assuming that similar pathophysiologic mechanisms are present in human pre- term infants, microglia and NMDA receptors could represent key targets for treatment of PVL.     

The effects of oxytocin and milk removal on milk secretion in the goat

1. When goats were milked each hour after being given a dose of synthetic oxytocin within the range thought to be released by the pituitary, there was a progressive rise in milk yield becoming statistically significant by 5 hr. The effect was reduced if the milk was not removed from the gland each hour.2. Milking transplanted glands each hour without injecting oxytocin also increased milk yield. The yield of the unmilked glands on the same animals was not affected. Massaging the transplanted glands had no effect on the milk yield.3. Oxytocin treatment and, to a lesser extent, frequent milking without oxytocin, altered milk composition. [Na], [Cl] and [non-casein protein] increased; [K] and [lactose] decreased.4. Oxytocin infusions permitted the leakage of [(14)C]lactose from milk to plasma and [(14)C]sucrose from plasma to milk.5. In some goats very small doses of oxytocin caused changes in milk composition and in one such animal these changes were mimicked by the close arterial infusion of bradykinin.6. Reasons are given for believing that the changes in composition are incidental to the main action of oxytocin in expelling milk and could be caused by a small number of leaks between the tight junctions connecting secretory cells.7. The increase in the rate of milk secretion following milk removal is probably of greater physiological significance than the small changes in milk composition and supports Levy's idea of a local negative feed-back via a chemical component of milk.     

Changes in sleep--waking cycle induced by lesions of medialis dorsalis thalamic nuclei in the cat

Bilateral lesions of medialis dorsalis (MD) thalamic nuclei in chronically implanted cats disrupt the sleep-waking cycle by inducing a reduction of both slow-wave and desynchronized sleep and a corresponding increase of wakefulness. Bilateral lesions of the anterior thalamic group produce some postural deficits but no changes in the percentage of sleep and wakefulness. The hypothesis that MD lesions alter the sleep processes by interrupting an anterior forebrain-MD-cortical link has been put forward.     

Elimination of paradoxical sleep by lesions of the pontine gigantocellular tegmental field in the cat.

Bilateral lesions of the pontine gigantocellular tegmental field in the cat resulted in the complete elimination of paradoxical sleep during 3 weeks postoperative recording. The tonic muscular atonia, normally characteristic of this state, was absent. The phasic components, rapid eye movements and ponto-geniculooccipital (PGO) spikes, did not occur in association with an activated EEG, as they normally do in paradoxical sleep. In fact, PGO spikes were virtually absent immediately after the lesion and were only secondarily apparent as isolated phenomena during slow wave sleep to represent in total daily number 5% of normal the first week and 15% of normal the third week after the lesion. These results indicate that neurons whose perikarya and/or processes are located within the pontine gigantocellular tegmental field and which are not part of the noradrenaline locus coeruleus complex, are critical for paradoxical sleep.     

Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study

Twenty-five male alcoholic Korsakoff patients were compared with age and sex-matched non-Korsakoff chronic alcoholics and healthy volunteers on clinical and CT brain scan parameters. The scans were assessed by planimetry, visual grading procedures and computerized analysis. Reliable measures of third ventricular size were developed. The Korsakoff patients had wider third ventricles, larger lateral ventricles and wider interhemispheric fissures than the comparison groups; but sulcal and Sylvian fissure widths were equivalent in Korsakoff and non-Korsakoff alcoholics. The results suggest that, in addition to their well-established diencephalic lesions, many Korsakoff patients have sustained widespread cerebral damage. Shrinkage in the frontal brain regions appears to be especially pronounced. The implications for a dual aetiology of alcoholic Korsakoff's syndrome involving thiamine deficiency and features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed.     

Thermosensory defects after cervical spinal cord lesions in the cat

Summary The behavioural thermosensitivity of cat paws was examined before and/or after restricted uni- and/or bilateral lesions had been made in the spinal cord between the first and fifth cervical segments. Unilateral lesions of the lateral funiculus, which involved at least its whole width at the level of the central canal, reproducibly were found to interfere with the contralateral sensitivity for temperature increases and/or decreases. No corresponding thermosensory deficiencies were found after unilateral lesions involving the ventral spinal quadrant or the dorsal funiculus. Various bilateral and combined lesions were made, but no cat ever developed thermoanaesthesia. The bilateral lesions included bilateral transections of: the middle parts of the lateral funiculi, the dorsal halves of the lateral funiculi, the dorsal funiculi, and the ventral spinal half.Most of our knowledge about peripheral behavioural thermosensitivity after spinal cord injury is based on observations of human patients, especially after anterolateral chordotomies. The present finding of contralateral thermosensory deficiencies after lesions of the middle part of the lateral funiculus fits with some of the clinical reports. The present failure to cause thermoanaesthesia, on the other hand, is inconsistent with the theory of a single ascending spinal pathway for behavioural thermo-sensitivity, which has emanated mainly from the clinical observations.     

Effects of unilateral flocculus lesions on vestibulo-ocular responses in the cat

Unilateral lesions of the cerebellar flocculus were performed in three chronically-implanted adult cats. Following the lesion a spontaneous nystagmus was observed in the dark, with the fast phase directed to the lesioned side. Vestibulo-ocular responses in the dark became asymmetrical. Responses to velocity steps exciting the labyrinth ipsilateral to the lesion were strongly increased. A decrease, although less marked, was observed in the opposite direction. Responses to sinusoidal oscillations in the dark were also asymmetric with respect to both the cumulative eye displacement during rotation in the two directions and the interval between two consecutive reversals of eye movement. These differences were greater at the lower tested frequencies (0.01 HZ) than at the higher (0.1 HZ). Spontaneous nystagmus disappeared in about 10 days and a complete symmetry of the vestibulo-ocular responses was restored in about 3 weeks. It is concluded that a unilateral lesion of the flocculus leads to two separate, but interacting, effects upon vestibulo-ocular responses.