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Urokinase-type plasminogen activator expression by neurons and oligodendrocytes during process outgrowth in developing rat brain.

The expression of tissue- and urokinase-type plasminogen activators has been studied in developing cerebellum, hippocampus, cerebral cortex, olfactory bulb and olfactory mucosa of the rat by in situ hybridization. All identifiable neurons express urokinase mRNA from an early stage in their development, and this expression appears to coincide with the onset of axogenesis. For cerebellar granule cells, both axonal growth and urokinase expression are initiated before they migrate from the external granule layer; for the majority of neocortical neurons, however, both processes are commenced after the cells have migrated to the cortical plate. Neurons continue to express this protease in the adult. The large projection neurons exhibit the highest levels of message, the smaller interneurons having much lower levels except for hippocampal granule cells, which have notably high levels of expression. Glial cells generally do not express urokinase message, except for transient expression by oligodendrocytes in developing fibre tracts during the period of myelination. Thus for both neurons and oligodendrocytes, the onset of urokinase-type plasminogen activator expression coincides with their initiation of major process outgrowth, although neurons maintain this expression in the adult, possibly to retain a degree of synaptic plasticity. In contrast, although high levels of message for the related protease, tissue plasminogen activator, are found in the embryonic floor plate, in postnatal brain it is abundantly expressed only by ventricular ependymal cells and by cells in connective tissue surrounding the olfactory nerve.

Animals↗

Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit.

Experiments have been made to determine the main route by which radio-iodinated albumin reaches deep cervical lymph from cerebrospinal fluid (c.s.f.) in the anaesthetized rabbit. Other factors, influencing drainage through this pathway, have been investigated. After single injection of [125I]albumin into a lateral ventricle of control rabbits, a mean of 14.8% of the radioactivity lost from brain-c.s.f. was recovered during 6 hr in the lymph of the cannulated jugular trunk of one side. Injection of kaolin into the olfactory fossa or sealing of the cribriform plate with cyanoacrylate glue reduced the recovery of [125I]albumin to 3.3% and 1.9% respectively at 2-3 weeks after the procedure designed to block the cribriform plate. This confirms the traditional view that the major connexions between c.s.f. and deep cervical lymph is via prolongations of subarachnoid space around the olfactory nerves, leading into the interstitial spaces of the nasal submucosa. The dense lymphatic plexus in this tissue is known to drain into the retropharyngeal (deep cervical) lymph nodes. Constant infusion of artificial c.s.f. into a lateral ventricle at 10 microliters/min or 30 microliters/min, in order to approximately double or quadruple flow through the system respectively, decreased the recovery of intraventricular [125I]albumin to 8.1% and 6.9% respectively. It also appeared that the increased c.s.f. pressures induced forced relatively more radioactivity from inside the skull into the c.s.f. spaces of the spinal cord. Maintaining the rabbit prone but at 20 degrees from the horizontal caused recoveries of [125I]albumin in lymph of 17.6% (head-up position and 6.6% (head-down). The amounts of radioactivity in nose and spinal cord markedly increased and decreased respectively in the head-down position. They changed in the opposite directions in the head-up position. The amounts of [51Cr]EDTA, [125I]metrizamide and [14C]inulin in deep cervical lymph were negligible after intraventricular injection. Estimations of the ratio of [51Cr]EDTA/[125I]albumin in various tissues on the pathway into lymph, together with measurements of arterio-venous fluxes across the retropharyngeal nodes, indicate that [51Cr]EDTA passed from c.s.f./lymph into blood within both the nose and the lymph nodes.

Albumins↗

Odor discrimination in pigeons.

An operant procedure was employed to investigate odor discrimination in the pigeon. Amyl acetate concentrations of 6-percent saturation in air, and lower, when paired with electric shock markedly reduced key-pecking during the odor stimulus period. Sectioning the olfactory nerves eliminated this selective suppression behavior. After the operation, the suppression was again conditioned when the concentration of amyl acetate was increased to 15-percent saturation in air. This is theoretically possible through mediation by the trigeminal system.

Acetates↗

Pathogenesis of Borna disease in rats: evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation.

Borna disease virus is an uncharacterized agent that causes sporadic but fatal neurological disease in horses and sheep in Europe. Studies of the infection in rats have shown that the agent has a strict tropism for neural tissues, in which it persists indefinitely. Inoculated rats developed encephalitis after an incubation period of 17 to 90 days. This report shows that the incubation period is the time required for transport of the agent in dendritic-axonal processes from the site of inoculation to the hippocampus. The immune responses to the agent had no effect on replication or transport of the virus. The neural conduit to the brain was proven by intranasal inoculation of virus that resulted in rapid transport of the agent via olfactory nerves to the hippocampus and in development of disease in 20 days. Virus inoculation into the feet resulted in spread along nerve fibers from neuron to neuron. There was sequential replication in neurons of the dorsal root ganglia adjacent to the lumbar spinal cord, the gracilis nucleus in the medulla, and pyramidal cells in the cerebral cortex, followed by infection of the hippocampal neurons and onset of disease. This progression required 50 to 60 days. The exclusiveness of the neural conduit was proven by failure to cause infection after injection of the virus intravenously or into the feet of neurectomized rats.

Animals↗

Primary amoebic meningoencephalitis in Britain.

Primary amoebic meningoencephalitis is caused by amoebae of the genera Naegleria and Hartmannella (Acanthamoeba), which ordinarily are free-living saprophytes. The infection may be acquired from fresh water-for example, while bathing-the amoebae invading the nasal mucosa and reaching the meninges and brain along the olfactory nerve filaments. The disease is designated "primary" to distinguish it from meningocerebral infection caused by the parasitic amoebae, particularly Entamoeba histolytica, which invade the central nervous system only as a result of dissemination in the blood stream from lesions in other parts of the body.During histological reappraisal of old specimens in a medical museum in London an instance of amoebic meningoencephalitis histologically indistinguishable from the published cases has been found. The specimen dates from 1909. The patient was said to be from Essex. What may have been another case, seen in Northern Ireland in 1937, is also described briefly. These observations may indicate that this disease occurs in the British Isles.Primary amoebic meningoencephalitis should be considered in the differential diagnosis of every case of acute meningitis.

Adolescent↗

Olfactory impairment in motor neuron disease: a pilot study.

The ability to identify smells was tested in nine males and six females with motor neuron disease (MND) of varying severity, using the University of Pennsylvania Smell Identification Test (UPSIT). The olfactory impairment found in MND patients compared with age and sex matched controls is statistically significant at the 0.005 level. The relationship with Parkinson's disease, with Alzheimer's dementia and the possible aetiological implications of this new aspect of the MND are discussed.

Aged↗

Drainage of interstitial fluid from different regions of rat brain.

Studies were carried out in anesthetized rats comparing dynamics and pathways of interstitial fluid (ISF) drainage from different regions of brain. Rates of drainage from brain and flow into cerebrospinal fluid (CSF) were estimated from the efflux from brain and influx into CSF of radioiodinated albumin (RISA) following microinjection into caudate nucleus, internal capsule, or midbrain: pathways of flow through the subarachnoid space and into lymph were traced from the distribution of horseradish peroxidase and/or Evans blue-labeled albumin after injection into brain. ISF drainage rates (mul X g brain-1 X min-1) estimated for the three injection sites were 0.18, 0.19, and 0.29, respectively. Flow of ISF into bulk CSF sampled from the cisterna magna accounted for 60-75% of efflux from midbrain but only 10-15% of efflux from caudate nucleus or internal capsule. RISA was concentrated in the subarachnoid space, relative to bulk CSF, in sleeves of adventitial tissue surrounding pericerebral arteries, possibly accounting for the low recovery of isotope from bulk CSF. From the subarachnoid space, some fluid drained via olfactory nerve sheaths to retropharyngeal lymph nodes.

Animals↗