Intracerebroventricular angiotensin II increases arterial blood pressure in rhesus monkeys by stimulation of pituitary hormones and the sympathetic nervous system

Summary Intracerebroventricular injections of angiotensin II in anesthetized rhesus monkeys increase systemic blood pressure and heart rate. These effects are accompanied by an increase in plasma ADH, cortisol, adrenaline and noradrenaline. Angiotensin II may participate in central mechanisms of blood pressure regulation by its stimulatory effect on the sympathetic nervous system, on ADH and on ACTH release in primates.     

Effect ofSchistosoma mansoni on plasma cholinesterase activity in rhesus monkeys

Summary A significant reduction in plasma cholinesterase activity at a time when fecal egg counts indicated a patent infection has been found in a limited study with schistosome infected Rhesus monkeys.     

Degeneration of the peripheral and central nervous system in vitamin-B12-deficient monkeys

Resumen Monos cautivos mantenidos en una dieta vegetariana presentaron niveles séricos de vitamina B₁₂ reducidos y lesiones en el sistema nervioso central semejantes a las de la «degeneración combinada sub aguda» del humano. Los nervios periféricos mostraron desmielinización segmentaria, compatible con un compromiso de las células de Schwann al azar. Usualmente hubo remielinización segmentaria, asociada a veces con degeneración axónica (walleriana). No se encontró evidencia de remielinización o de regeneración axónica que pudiera ser atribuída totalmente al tratamiento con vitamina B₁₂.     

A central nervous system effect of a non-hallucinatory lysergic acid derivative

Zusammenfassung Ähnlich wie Serotonin und LSD-25 vermindert BOL-148, ein Lysergsäurederivat, das keine Halluzinationen erzeugt, die durch den Balken fortgeleiteten, postsynaptischen Potentiale. Vorbehandlung mit BOL-148 macht das Versuchstier für ungefähr eine Stunde unempfindlich gegen Serotonin. BOL-148 blockiert anscheinend im Zentralnervensystem wie auch in der Peripherie den Serotonineffekt. Es wird versucht, zu erklären, weshalb diese Droge keine Halluzinationen bewirkt.     

On the catechol amine levels in blood plasma after stimulation of the sympathoadrenal system

Zusammenfassung Stimulation des sympathicoadrenalen Systems der atropinisierten Katze mit Carbacholin ergab signifikante Mengen von Adrenalin und Noradrenalin im Blutplasma. Bei intakter Nebenniere dominierte Adrenalin, nach Adrenalektomie Noradrenalin. Die Freisetzung von Adrenalin oder Noradrenalin unterblieb bei mit Reserpin vorbehandelten adrenalektomierten Tieren.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 micrograms of 18-OH-DOC dissolved in 0.5 ml of a 4:1 saline Cremophor-EL solution were injected i.v. A decrease of 55.7 +/- 6.1% in the amplitude of the EPs was observed with the hormone 16.3 min +/- 2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min +/- 6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

Summary The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 g of 18-OH-DOC dissolved in 0.5 ml of a 41 saline Cremophor-EL solution were injected i.v. A decrease of 55.7±6.1% in the amplitude of the EPs was observed with the hormone 16.3 min±2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min±6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

Multitasking with neurotensin in the central nervous system

The 13-amino acid peptide neurotensin (NT) was discovered over 30 years ago and has been implicated in a wide variety of neurotransmitter and endocrine functions. This review focuses on four areas where there has been substantial recent progress in understanding NT signaling and several functions of the endogenous peptide. The first area concerns the functional activation of the high-affinity NT receptor, NTR-1, including the delineation of the NT binding pocket and receptor domains involved in functional coupling to intracellular signaling pathways. The development of NT receptor antagonists and the application of genetic and molecular genetic approaches have accelerated progress in understanding NT function in several areas, including the involvement of NT in antipsychotic drug actions, psychostimulant sensitization and the modulation of pain, and these are reviewed in that order. There is now substantial evidence indicating that NT is required for certain antipsychotic drug actions and that the peptide plays a key role in stress-induced analgesia.Received 18 March 2005; received after revision 9 May 2005; accepted 23 May 2005     

The potential therapeutic role of statins in central nervous system autoimmune disorders

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.Received 17 April 2003; received after revision 21 May 2003; accepted 22 May 2003     

Heat shock response in the central nervous system

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemis stress confers protection from a subsequent ischemic insult.     

The role of apolipoprotein E in lipid metabolism in the central nervous system

The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover, although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004     

Neurotrophins and neuronal differentiation in the central nervous system

The central nervous system requires the proper formation of exquisitely precise circuits to function properly. These neuronal circuits are assembled during development by the formation of synaptic connections between hundreds of thousands of differentiating neurons. For these circuits to form correctly, neurons must elaborate precisely patterned axonal and dendritic arbors. Although the cellular and molecular mechanisms that guide neuronal differentiation and formation of connections remain mostly unknown, the neurotrophins have emerged recently as attractive candidates for regulating neuronal differentiation in the developing brain. The experiments reviewed here provide strong support for a bifunctional role for the neurotrophins in axonal and dendritic growth and are consistent with the exciting possibility that the neurotrophins might mediate activity-dependent synaptic plasticity.