An immunohistochemical and fine-structural analysis of peptidergic hypothalamic neurosecretory axon regeneration into the leptomeninges of the rat.

Regeneration of severed hypothalamic peptidergic neurosecretory axons into the ventral pia-arachnoid was observed in rats at the light microscopic and fine-structural levels. A temporal increase occurred in the number of neurophysin-positive axons regenerating into the leptomeninges for distances up to 3.3 mm by 40 days post-lesioning. A consistent pattern of parallel, meshed and clustered axons, occurring either singly or in bundles, was present within the connective tissue, while plexus and bundles were observed in association with leptomeningeal blood vessels. Axons were characterized by preterminal and terminal dilatations. Neurosecretory granulated vesicles occurred throughout axons. The presence of microvesicles at contact points with basal lamina suggests the possibility of hormone release. Most axons were arranged as fascicles associated closely with basal lamina-bounded support cells whose thin lamellar processes wrapped single axons or fascicles of axons. We conclude, therefore, that cellular and intercellular leptomeningeal microenvironments support and sustain the growth and regeneration of transected neurosecretory axons.

Neurosecretory axon regeneration into intrahypothalamic neural lobe allografts: neurophysin immunohistochemistry and fine structure.

Neural lobe allografts placed stereotactically into the hypothalamo-neurohypophysial tract between the paraventricular and supraoptic nuclei were investigated between 5 and 70 days post-transplantation (dpt). They contained temporally increasing numbers of neurophysin-positive axons. At the fine structural level, endogenous neurosecretory axons had virtually disappeared from successful (vascularized) grafts by 5 dpt. At this time, single host neurosecretory axons and especially numerous growth cones were associated with pituicyte processes and/or scalloped basal lamina scaffolds. Axon terminals containing neurosecretory granulated vesicles and microvesicles were present only occasionally at 5 dpt but became much more numerous subsequently. These terminals were associated with pituicytes and abutted the parenchymal basal lamina of pericapillary connective tissue spaces. In addition, beginning at 10 dpt, neurolemmocyte-like cells were associated with neurosecretory axons. At 70 dpt, the fine structural characteristics of grafted neural lobes were virtually indistinguishable from those of intact controls, except for the presence of occasional areas of more extensive connective tissue, nonfenestrated capillaries and neurolemmocyte-like cells.

Fine structural characteristics of neurophysin-positive perivascular plexus that develop in the rat hypothalamus following interruption of the hypothalamo-neurohypophysial tract.

Transection of neurosecretory axons of the hypothalamo-neurohypophysial tract within the hypothalamus by stereotactic grafts of various tissues or knife cuts induced the development of neurophysin-positive plexus around arterioles, venules and capillaries in the vicinity of these grafts or cuts. These plexus ranged from single axons to densely woven networks and tended to increase progressively with time after experimental intervention. At the fine structural level, typical neurosecretory axon profiles were either abutting the perivascular connective tissue space or located within it. They were usually accompanied by astrocyte processes or microglial cells. Many of these axons had extensive contact with the surrounding basal lamina at which point clusters of microvesicles reminiscent of axon terminals in the neural lobe were present.

Insulin-induced elevation of hypothalamic norepinephrine turnover persists after glucorestoration unless feeding occurs.

We employed a delayed feeding paradigm to assess regional brain catecholamine changes associated with insulin-elicited glucoprivic feeding. This paradigm makes use of the recent discovery that glucoprivic challenges significantly enhance food intake even when food is withheld until other signs of glucoprivation have abated. Using this paradigm we attempted to temporally dissociate the neurochemical events associated with the ingestive response from other potentially confounding consequences of insulin or glucoprivation. We found a high degree of congruence between elevated hypothalamic norepinephrine (NE) turnover (estimated by the change in transmitter concentration after synthesis inhibition) and the persistence of hunger, both during and after apparent glucoprivation. In the absence of food, hypothalamic NE turnover was enhanced during insulin-induced glucoprivation and this increase persisted into the postglucoprivic period. A brief feeding bout, either during glucoprivation or postglucoprivically, rapidly normalized NE turnover rates. Moreover, brief access (30 min) to a limited quantity of food (2.5 g) during glucoprivation abolished both the elevated turnover and the feeding response otherwise observed postglucoprivically. Turnover of catecholamines in the telencephalon was also enhanced after insulin, but the increased activity did not persist into the postglucoprivic period and, in addition, was not altered in any consistent manner by food intake. These findings strengthen the view that hypothalamic NE neurons are involved in the mediation of glucoprivic feeding.

Anticonvulsant properties of ropizine in epileptic and nonepileptic beagle dogs.

Studies were conducted on a colony of purebred beagle dogs. Animals with spontaneous seizures were classed as epileptic beagles (EB). Those without spontaneous seizures were termed nonepileptic beagles (NEB). The median convulsant current for maximal electroshock seizure (MES) threshold was 175(194-158)mA for EB and 390 (417-364) mA for NEB. Similarly the median convulsant dose of pentylenetetrazol (PTZ) was 7.9 (10.1-6.2) mg/kg for EB and 20.2 (24.2-17.6) mg/kg for NEB. Following pretreatment with graded doses of ropizine (SC 13504), the median protective dose against MES was 6.0(9.2-3.9) mg/kg in EB and 3.2(4.8-2.1) mg/kg in NEB. Based on the incidence of ataxia, EB had a median toxic dose (TD50) of 14.0(16.5-11.9) mg/kg, while in NEB it was 18.0(23.6-13.7)mg/kg. The TD50 doses were unable to protect against a convulsive dose of PTZ. It is concluded first that ropizine may have anti-grand mal activity but apparently lacks an anti-petit mal action. Secondly, EB are more sensitive than NEB to the convulsive effects of electric current and PTZ, yet less responsive to the anticonvulsant actions of ropizine.