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In the present study, we investigated whether high-pressure hypotonic saline solution (Hphss) affects the basal level of Nerve Growth Factor (NGF) and expression of receptors in the cochlea, bark earing, retina, and visual cortex.For this study, we used three weeks old female Sprague Dawley (SD) rats (n = 12). Rats were housed in polypropylene cages and were kept under standard conditions (12 h light:12 h dark cycle) with free access to water and food (Purina chow food). A specific dispenser was employed to deliver sterile hypotonic saline at high pressure (pressing emission level (PEL): 7 g/s; emission time (ET): 0.5 s). Rats were divided into two groups: untreated (n = 6) and treated with Hphss (n = 6), three times per day, for 10 consecutive days. Treatment was performed in both nostrils with 50 µl of Hphss using a microsyringe equipped with a plastic tip.We observed a significant enhancement in the level of NGF in the cochlea and bark earing, but not in the retina and visual cortex. This is likely because the nasolacrimal duct pathway does not appear to have an effect on the retina, and the visual cortex appears to be too far from the cribriform plate to be reached by nasal NGF.This treatment can significantly protect and/or delay degeneration of cochlear auditory NGF-target cells. It is free from side effects and can be used in chronic diseases for as long as needed. It remains to be investigated whether the effects of short-term therapy are long-lasting, or if the treatment must be repeated.

Nerve growth factor (NGF) is a neurotrophin which promotes and regulates the survival of neurons in the peripheral nervous system. The aim of this study was to investigate the effect of high-pressure administration of sterile physiological saline isotonic solution (HpPSIS) into nasal cavity of laboratory animals on NGF levels and NGF-receptor expression in the olfactory bulbs and brain.For this study we used three weeks old female Sprague Dawley SD rats (n=48). Rats were divided into two groups, the first one treated delivering physiological saline solution with a normal syringe modified at the extremity to fit the rats' nostril (5 ml) (n=24) and the second one treated spray with HpPSIS (n=24 rats). Rats were treated three times a day either for 5 consecutive days (shorth term treatment) or 10 consecutive days (longer treatment) in both nostrils of HpPSIS delivered at high pressure (pression emission level: PEL: 7 g/sec for emission time ET: 0.5 sec) with a specific forced spray erogator. Untreated rats received a similar manipulation three times a day through a syringe in the nostrils, but no HpPSIS administration.The results of these studies highlight the possibility that endogenous enhancement of NGF by stimulation of NGF-producing cells within the nasal cavities and also in the CNS represent a novel experimental approach to enhance the brain NGF levels with a new therapy. HpPSIS treatment further enhances the presence of NGF in the four brains examined. Indeed, a significant increase of NGF was first observed after 5 days of HpPSIS treatment, compared to HpPSIS untreated rats. The increase was over 25% in the OB, ST, HI and in CX, while 10 days after HpPSIS treatments the levels of NGF were even higher. These differences were statistically significant, p0.05.It was found that forced administration of HpPSIS enhances the presence of these neurotrophic signals, not only in the olfactory bulbs, but also in forebrain cholinergic neurons, which are known to degenerate as result of memory loss and brain aging, including Alzheimer Disease. These findings for the first time in the literature demonstrate the possibility of enhancing the endogenous NGF to protect NGF-damaged neurons. Since the enhanced expression of NGF was first observed after 5 days of treatment and higher after 10 days of treatment, a reasonable hypothesis is that longer HpPSIS treatment might further enhance the level of NGF in brain and olfactory bulbs.

The aging brain is characterized by selective neurochemical changes involving several neural populations. A deficit in the cholinergic system of the basal forebrain is thought to contribute to the development of cognitive symptoms of dementia. Attempts to prevent age-associated cholinergic vulnerability and deterioration therefore represent a crucial point for pharmacotherapy in the elderly. In this paper we provide evidence for the protective effect of nicergoline (Sermion) on the degeneration of cholinergic neurons induced by nerve growth factor deprivation. Nerve growth factor deprivation was induced by colchicine administration in rats 13 and 18 months old. Colchicine induces a rapid and substantial down-regulation of choline acetyltransferase messenger RNA level in the basal forebrain in untreated adult, middle-aged and old rats. Colchicine failed to cause these effects in old rats treated for 120 days with nicergoline 10 mg/kg/day, orally. Moreover, a concomitant increase of both nerve growth factor and brain-derived neurotrophic factor content was measured in the basal forebrain of old, nicergoline-treated rats. Additionally, the level of messenger RNA for the brain isoform of nitric oxide synthase in neurons of the basal forebrain was also increased in these animals. Based on the present findings, nicergoline proved to be an effective drug for preventing neuronal vulnerability due to experimentally induced nerve growth factor deprivation.

Our acute awareness of the cosmetic, psychosocial and sexual importance of subcutaneous adipose tissue contrasts dramatically with how poorly we have understood the biology of this massive, enigmatic, often ignored and much‐abused skin compartment. Therefore, it is timely to recall the exciting, steadily growing, yet underappreciated body of evidence that subcutaneous adipocytes are so much more than just ‘fat guys’, hanging around passively to conspire, at most, against your desperate attempts to maintain ideal weight. Although the subcutis, quantitatively, tends to represent the dominant architectural component of human skin, conventional wisdom confines its biological key functions to those of energy storage, physical buffer, thermoregulation and thermoinsulation. However, already the distribution of human superficial adipose tissue, by itself, questions how justified the popular belief is that ‘skin fat’ (which actually may be more diverse than often assumed) serves primarily thermoinsulatory purposes. And although the metabolic complications of obesity are well appreciated, our understanding of how exactly subcutaneous adipocytes contribute to extracutaneous disease – and even influence important immune and brain functions! – is far from complete. The increasing insights recently won into subcutaneous adipose tissue as a cytokine depot that regulates innate immunity and cell growth exemplarily serve to illustrate the vast open research expanses that remain to be fully explored in the subcutis. The following public debate carries you from the evolutionary origins and the key functional purposes of adipose tissue, via adipose‐derived stem cells and adipokines straight to the neuroendocrine, immunomodulatory and central nervous effects of signals that originate in the subcutis – perhaps, the most underestimated tissue of the human body. The editors are confident that, at the end, you shall agree: No basic scientist and no doctor with a serious interest in skin, and hardly anyone else in the life sciences, can afford to ignore the subcutaneous adipocyte – beyond its ample impact on beauty, benessence and body mass.

We have studied the neuropathological characteristics of the brain of rats receiving daily intracerebroventricular administration of freshly dissolved human immunodeficiency virus type 1 recombinant protein gp120 (100 ng per rat per day) given for up to 14 days. Histological examination of serial brain sections revealed no apparent gross damage to the cortex or hippocampus, nor did cell counting yield significant neuronal cell loss. However, the viral protein caused after 7 and 14 days of treatment DNA fragmentation in 10% of brain cortical neurons. Interestingly, reduced neuronal nitric oxide synthase (NOS) expression along with significant increases in nerve growth factor (NGF) were observed in the hippocampus, where gp120 did not cause neuronal damage. No changes in NGF and NOS expression were seen in the cortex, where cell death is likely to be of the apoptotic type. The present data demonstrate that gp120-induced cortical cell death is associated with the lack of increase of NGF in the cerebral cortex and suggest that the latter may be important for the expression of neuropathology in the rat brain. By contrast, enhanced levels of NGF may prevent or delay neuronal death in the hippocampus, where reduced NOS expression may be a reflection of a subcellular insult inflicted by the viral protein.

Type 1 diabetes mellitus (DM), a "classical" result of a pancreatic-beta cell damage, is associated with various metabolic, neuronal, endocrine and immune alterations at cellular, tissue and organ levels. Nerve growth factor (NGF) is one of the most extensively studied neurotrophic factors, which is produced and released by numerous cells including the pancreatic beta cells. NGF plays an important role during brain development and may be able to delay or even reverse damaged forebrain cholinergic neurons that undergo degeneration in aged animals and in Alzheimer's disease (AD). Recent reports indicate that experimentally induced DM in rodents can cause brain biochemical and molecular alterations similar to those observed in sporadic AD. Given the importance of NGF in the pathophysiology of brain cholinergic neurons, we looked for NGF changes in the pancreas and brain of diabetic rats. The aim of this study was, therefore, to investigate the effect of streptozotocin-induced DM on NGF and NGF receptor expression in pancreas and brain. The results showed that DM is associated with altered NGF, NGF-receptor expression in both pancreas and brain.

Cholecystokinin-8 (CCK-8), the small peptide initially described as a gastric factor involved in the regulation of feeding behavior, is today recognized as one of the most abundant neurotransmitters/ neuropeptides in brain and is an important signal factor for the peripheral and central nervous systems. In the past twenty years, many studies have focused on possible clinical applications of this peptide and its receptor ligands in psychiatric diseases and gastrointestinal pathologies. Recently it has been suggested that CCK-8 may also have a neuroprotective role, thus opening a new field of interest around the physiology and the pharmacology of this neuropeptide and its receptors. It has been demonstrated that CCK-8 counteracts neuronal deficit following chemical or surgical lesions in both the central and peripheral nervous systems and that Nerve Growth factor (NGF) is involved in the CCK-induced recovery process. By using selective CCK receptor antagonists it has been demonstrated that CCK-8, when injected intraperitoneally, has the ability to stimulate NGF synthesis in brain and peripheral organs by a mechanism that involves the activation of CCK receptors. As has been widely reported, NGF is an essential survival and differentiative factor for selective neuronal populations of the PNS and CNS and plays a role in the events of degeneration and repair of the nervous system in diseases with different etiologies, e.g. neurodegenerative and autoimmune diseases as well as diabetes-associated pathologies. The possibility of using NGF in therapy has been evaluated and systemic and intracerebral NGF treatment have been tested in patients and animal models. Although the results of these studies are encouraging, the difficulty to predict and/or eliminate the side effects of NGF/NGF antibody treatment has made it difficult to fully evaluate the potential of the beneficial effects. In this context recent results obtained in our laboratories may offer a new prospective for the pharmacological approaches to the diseases associated with altered NGF production and functions. The data of our recent observations on NGF and CCK-8 is covered in this review.

The biological effects of Nerve Growth Factor (NGF) are primarily mediated via its high affinity receptor-TrkA. In the present study, we examined the effect of experimental autoimmune encephalomyelitis (EAE) upon the expression of TrkA in neuronal and non-neuronal cells of the spinal cord of Lewis rats during the acute (14 days postimmunization) and chronic (12 months postimmunization) phases of the disease. In the normal spinal cord, both of mature and aged rats, we found TrkA immunoreaction (TrkA-IR) in the motoneurons of the Rexed lamina IX and in both oligo- and astroglia cells. In the acute phase of the disease, we found a reduction of TrkA immunoreactivity in motoneurons and its up-regulation in oligodendroglia, mainly in the white matter. We also confirmed our previous findings concerning the up-regulation of TrkA-IR in astroglia. Both neuronal and non-neuronal changes of TrkA immunoreactivity had a transient character: they were not seen in the chronic phase of the disease. Our results suggest that both neuronal and glial TrkA expression changes depend on inflammation. Moreover, our data indicate that, during the acute phase of EAE, the glial cells become more receptive to NGF, pointing to glia as an important target for pharmacological manipulations, particularly for exogenously administered NGF.

Stress is elicited by environmental, social or pathological conditions occurring during the life of animals and humans that determine changes in the nervous, endocrine and immune systems. In the present review, we present data supporting the hypothesis that stress-related events both in animal models and humans are characterized by modifications of endogenous nerve growth factor (NGF) synthesis and/or utilization. Stress inducing alteration in NGF synthesis and/or utilization appears to be more severe during neurogenesis and in early postnatal life. However, NGF endogenously released during stress may promote remodeling of damaged tissues following acute and/or chronic stressful events.

Despite extensive research on the pathogenesis of polycystic ovary syndrome (PCOS), there is still disagreement on the underlying mechanisms. The rat model for experimentally induced polycystic ovaries (PCO)-produced by a single injection of estradiol valerate-has similarities with human PCOS, and both are associated with hyperactivity in the sympathetic nervous system. Nerve growth factor (NGF) is known to serve as a neurotrophin for both the sympathetic and the sensory nervous systems and to enhance the activity of catecholaminergic and possibly other neuron types. Electro-acupuncture (EA) is known to reduce hyperactivity in the sympathetic nervous system. For these reasons, the model was used in the present study to investigate the effects of EA (12 treatments, approximately 25 min each, over 30 days) by analyzing NGF in the central nervous system and the endocrine organs, including the ovaries. The main findings in the present study were first, that significantly higher concentrations of NGF were found in the ovaries and the adrenal glands in the rats in the PCO model than in the control rats that were only injected with the vehicle (oil or NaCl). Second, that repeated EA treatments in PCO rats resulted in concentrations of NGF in the ovaries that were significantly lower than those in non-EA-treated PCO rats but were within a normal range that did not differ from those in the untreated oil and NaCl control groups. The results in the present study provide support for the theory that EA inhibits hyperactivity in the sympathetic nervous system.

We have previously reported that administration of Thymosin alpha 1 (T-alpha1) can enhance the level of the Nerve Growth Factor and the distribution of its receptor in the developing Central Nervous System (CNS) of rat. To further explore the role of T-alpha1 and verify its presence in cells of rat CNS, we carried out an immunohistochemical study using a polyclonal antibody against T-alpha1. T-alpha1 immunoreactivity was found mainly in neurons of the hippocampus and spinal cord and in several small cells, resembling glial cells, of specific regions of the brain. Moreover, to study whether cerebral cells were receptive to T-alpha1, we injected iodinated T-alpha1 (125I-T-alpha1) i.c.v.. 125I-T-alpha1 labelled neurons were observed in the hypothalamus and septal nuclei. Our results indicate that specific neuronal populations in the rat CNS are able to express and respond to T-alpha1.

It has been reported that maternal ethanol consumption leads to deficits in the limbic areas involved in cognitive functions and interferes with synthesis and utilization of neurotrophins. In the present study, it was hypothesized that prenatal alcohol intake might induce neuroanatomical alterations in the entorhinal cortex (EC). We also investigated the possible EC involvement of brain nerve growth factor (NGF), the first neurotrophin to be isolated, during such pathological events. To test this hypothesis, we used pregnant mice exposed to ethanol during EC neurogenesis (starting about gestational day 8). Our data show that prenatal alcohol intake in male mice alters the EC neuronal growth and differentiation. These morphological alterations are accompanied by an altered NGF level in the EC of prenatal alcohol-treated mice. We also found a decrease in choline acetyltransferase- and neuropeptide Y-immunopositive neurons in the EC of alcohol-exposed mice. However, the relationship between neuronal damage induced in the EC by ethanol, low presence of NGF, and the possible functional and behavioral consequences remains to be elucidated.

Numerous studies published in the last two decades provide evidence that nerve growth factor (NGF), a polypeptide originally discovered because of its neurotrophic activity, acts on a variety of cells of the immune system, including mast cells, eosinophils, and B and T lymphocytes. NGF has been shown to increase during inflammatory responses, autoimmune disorders, parasitic infections, and allergic diseases. Moreover, stress, which is characterized also by activation of a variety of immune cells, causes a significant increase in basal plasma NGF levels. Recently published studies reveal that hematopoietic progenitor cells seem to be able to produce and/or respond to NGF. We report these data and discuss the hypothesis of the possible implication of NGF on the functional activities of immune cells.

The effect of subchronic intracerebroventricular injection of the human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given daily for up to seven consecutive days) on interleukin-1beta expression was studied by immunohistochemistry in the brain of adult rats. In comparison to control, bovine serum albumin (300 ng, given intracerebroventricularly for up to seven days) -treated animals (n=6), interleukin-1beta immunoreactivity increased in the brain cortex and hippocampus of rats (n=6) receiving a single injection of the viral protein 24 h before analysis with more substantial increases being observed in these regions of the brain (n=6) after seven days treatment. Double-labelling immunofluorescence experiments support a neuronal and, possibly, a microglial cell origin for gp120-enhanced interleukin-1beta expression. Transmission electron microscopy analysis of brain tissue sections revealed that combination treatments (given intracerebroventricularly daily for seven days) with gp120 (100 ng) and interleukin-1 receptor antagonist (80 ng) or with the interleukin converting enzyme inhibitor II (100 pmol), but not with leupeptin (100 pmol), prevented apoptotic death of rat (n=6/group) brain cortical cells typically elicited by the viral protein. These data demonstrate that gp120 enhances interleukin-1beta expression in the brain and this may be involved in the mechanism underlying apoptosis induced by gp120 in the brain cortex of rat. Further support to this hypothesis comes from the evidence that intracerebroventricular injection of murine recombinant interleukin-1beta (200 U, given daily for seven consecutive days) produces DNA fragmentation in the brain cortex of rat (n=6). Interestingly, the latter treatment enhanced nerve growth factor level in the hippocampus but not in the cerebral cortex and this coincides with a similar effect recently reported in identical brain areas of rats treated likewise with gp120. In conclusion, the present data demonstrate that treatment with gp120 enhances interleukin-1beta expression and this participates in the mechanism of apoptotic cell death in the brain cortex of rat. By contrast, in the hippocampus, gp120-enhanced interleukin-1beta expression elevates nerve growth factor that may prevent or delay apoptosis in this plastic region of the rat brain.

Background: Several studies provide evidence that nerve growth factor (NGF) has an expanding role in neuroimmune interactions. Methods: We review our data on circulation levels of NGF in allergic diseases as well as on the relationships between this neurotrophin and primary and secondary effector cells of allergic inflammation. Results: In vernal keratoconjunctivitis, a close relationship exists between the increased NGF plasma values and the number of mast cells infiltrating the conjunctiva. NGF serum values are also increased in other allergic diseases and asthma, and are related to the severity of the inflammatory process and disease. Human CD4+ T cell clones (preferentially of activated Th2 type) produce and release NGF, and express high–affinity NGF receptors. NGF is preformed in and can act on human peripheral blood eosinophils to preferentially release inflammatory mediators. Immunoreactivity for high affinity NGF receptors is present both in basal epithelial cells and in the inflamed stroma of the allergic conjunctiva. Topical administration of NGF results in a complete healing of neurotophic corneal ulcers in man, thus suggesting a profound effect of NGF on human fibroblasts and extracellular matrix. Conclusion: Data presented suggest that NGF is an important molecule in allergic inflammation and tissue remodelling occurring in allergic diseases.

We have previously shown that the level of nerve growth factor (NGF) undergoes significant changes in the cerebrospinal fluid of patients with Multiple Sclerosis and in the brain of rats affected by Experimental Allergic Encephalomyelitis (EAE). The functional significance of the endogenous disregulation of NGF is not known, though recent studies seem to suggest that NGF might be associated with the ability of oligodendrocytes (OLs) to produce and/or utilise NGF. The aim of the present study was therefore to investigate whether NGF is involved in the development and differentiation of cells of the subventricular zone (SVz) which arbors undifferentiated cells that can give rise to OLs. The results show that NGF injected into the brain of developing rats and of rats affected by EAE is retrogradely transported from the SVz to the brain parenchyma. These findings suggest that during the early phase of brain development and during EAE, NGF, along with other growth factors, is implicated in growth and/or differentiation of OLs and in protecting neuronal injury. The possible functional role of NGF in these events has been discussed.

Fas is a receptor of the tumor necrosis factor (TNF)/ nerve growth factor (NGF) receptor superfamily that mediates apoptosis and some inflammatory changes. As the central administration of TNF is known to activate the hypothalamus-pituitary-adrenal axis (HPAA) and to induce peripheral responses including induction of serum interleukin (IL)-6 and serum amyloid A (SAA), we investigated the effects of intracerebroventricular (i.c.v.) administration of agonist anti-Fas monoclonal antibody Jo2. Centrally administered anti-Fas (1 microg/mouse, i.c.v.) induced elevated levels of corticosterone, IL-6, and SAA comparable to those observed after i.c.v. administration of recombinant murine TNF. On the other hand, administration of murine NGF did not elevate serum corticosterone or IL-6, but induced SAA. Thus, Fas can trigger a centrally mediated anti-inflammatory response (HPAA activation) and induce a peripheral acute-phase response comparable to that induced with TNF, whereas NGF induces only acute-phase proteins.

Nerve growth factor (NGF) is the first discovered and best known neurotrophic factor and is required for the survival and differentiation of a variety of neuronal cell types in both the peripheral and central nervous system. Recent studies indicate that NGF is synthesized by cells of immune system lineage and that its level increases during inflammatory responses, while cytokines such as interleukin-1 beta and tumor necrosis factor-alpha are potent inducers of NGF secretion. The role played by NGF on cells of the immune system was strengthened by recent evidence demonstrating that cells normally present in inflammatory tissues, such as mast cells and lymphocytes, express NGF receptors and are receptive to the action of NGF. Studies carried out in our and other laboratories showed that NGF is expressed in the synovial fluid of patients with rheumatoid arthritis and other forms of chronic arthritis, as well as in the synovium of pharmacologically-induced arthritis in animal models. Moreover, arthritic transgenic mice which carry and express the human tumor necrosis factor-gene also showed elevated levels of NGF. Significant increases in NGF levels have been found in the sera of patients with systemic lupus erythematosus and in the dermis of patients affected by systemic sclerosis. In this paper the hypothesis that NGF is involved in the pathophysiology of autoimmune rheumatic arthritis is discussed.

The presence of Nerve Growth Factor (NGF) and the expression of low- and high-affinity NGF receptor were investigated in prenatal, postnatal and pregnant rats. Using ELISA and immunohistochemistry it was found that both NGF and its receptors are present in the medulla of the thymus and are more strongly expressed in pre- and early postnatal life and nearly absent in adult and ageing rats. It was also found that during pregnancy, which is characterised by an involution of the cortex and hypertrophy of the medulla, the level of NGF in the thymus increases. The present study showed not only that NGF is produced in a specific compartment of the thymus, the medulla, but that its synthesis declines with age, following thymus involution. These results suggest that NGF may be critically involved in the proliferation and differentiation of thymic cells.

In a previous study it was shown that the levels of NGF in the cerebrospinal fluid of patients affected by multiple sclerosis (MS) increase during the acute phase of the disease and decrease in the remission phase. In the present study, using an animal model of MS, we investigate whether any changes in NGF levels occur in brains of rats affected by Experimental Allergic Encephalomyelitis (EAE). The results show an enhanced level of NGF in the thalamus and spinal cord and a numerical increase of mast cells (MCs) expressing mRNA-NGF localized in these two regions. These observations suggest that NGF is involved in EAE and that MCs contribute to the local increase of NGF.

In the adult mammalian central nervous system (CNS) the nerve growth factor (NGF) has thus far been associated mainly with the metabolic support and pathophysiology of cholinergic basal forebrain (CBF) neurons. Recently, however, the presence of NGF and NGF mRNA has been demonstrated in the hypothalamus of adult mice. In addition there have been reports on the stimulation of the pituitary-adrenocortical axis by NGF. These and other findings suggest the involvement of NGF in hypothalamic functioning. The aim of the present study was to improve immunohistochemical methodologies for the investigation of NGF and NGF-receptor (NGF-r) in the hypothalamus of adult rats. Our results show NGF and NGF-r expression in various regions of the hypothalamus. Moreover, in some areas, distribution and morphology of immunoreactive neurons suggest neuronal colocalization of the two markers. To study the function of NGF in the hypothalamus, anti-NGF antibody was injected in the area of the paraventricular nucleus. We did not, however, find an effect of treatment on NGF-r immunoreactive neurons in this area.

Recent studies have demonstrated that the action of nerve growth factor (NGF) is not restricted to neuronal cells but also affects cells of the immune system. In a previous work on the effect of NGF on the chick embryo bursa of Fabricius both in vivo and in vitro, we observed that NGF prolongs bursal cell survival in vitro. In the present study we report that the increase of viable cells in NGF-treated cultures is not due to a proliferative effect of NGF on bursal cells but to a reduction of cell mortality. The morphological analysis revealed that bursal cells in cultures die by apoptosis, which was also shown by the typical pattern of DNA fragmentation, a hallmark of this cell death process. It is concluded that NGF, with an action similar to that described in sympathetic neurons and PC12, could retard bursal cell death by influencing apoptosis.

In the present study the effect of alcohol consumption on brain nerve growth factor (NGF) and the NGF-target cells of adult male rats and pups exposed prenatally to ethanol is evaluated. It is hypothesized that NGF, a trophic agent for the survival and maintenance of basal forebrain cholinergic neurons, might be affected by the neurodegenerative events which occur during ethanol consumption. To test this hypothesis, we used adult rats exposed to ethanol for 16 weeks and pregnant rats exposed to ethanol for six days. Our experiments show that ethanol ingestion causes a reduction of NGF in the hippocampus, of choline acetyltransferase activity in both the septum and hippocampus, and in the distribution of NGF receptor in the basal forebrain cholinergic neurons. The results indicate that the damaging effect of alcohol on forebrain cholinergic neurons is also associated with impairment of central NGF-target structures.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the septum and hippocampus of the rat brain 7 days following partial electrolytic lesion (2 mA, 30 s) of the septohippocampal pathways or after single intraventricular administration of 15 U of interleukin-1 beta (IL-1 beta). A double immunostaining technique which allowed a simultaneous localization of NGF-LIR and that of astroglia marker glial fibrillary acidic protein was used. Our data show that after both treatments, apart from neuronal localization of NGF-LIR typical for normal brain, many astrocytes both in the septum and hippocampus became NGF-like immunoreactive. Besides, NGF-LIR often formed a "halo" reaction around astrocytes. These results support the notion that activated in vivo brain astrocytes may, just as astrocytes growing in vitro, synthesize and secrete NGF-like molecules. Our findings may be of importance in considerations concerning trophic support to the cholinergic neurons of the basal forebrain nuclei whose impaired function is essentially responsible for some cognitive deficits in neurodegenerative diseases such as Alzheimer disease.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the intact adult rat brain at the level of the hippocampus and the septum. Immunolabelling for NGF combined with counterstaining with cresyl violet and double immunostaining technique, which allowed simultaneous localization of NGF-LIR and that of astroglial marker -GFAP, were used. The data indicate neuronal localization of NGF-like immunoreactivity and a lack of colocalization of NGF-LIR with the immunoreactivity of GFAP in the hippocampus. These data are consistent with in situ hybridization results for NGF and immunocytochemical results for pro-NGF localization obtained by others. At the septal level, apart from neuronal localization of NGF-LIR, single NGF-like immunoreactive astrocytes have been observed. This suggests that, although to a very small extent, in vivo intact brain astrocytes may, just as astrocytes growing in vitro, synthesize NGF-like molecules. This finding may be of importance in better understanding the trophic support for NGF responsive cholinergic neurones in the brain.

The effect of levocarnitine acetyl on neurite regeneration was evaluated following administration of 6-hydroxydopamine which caused a selective degeneration of peripheral catecholaminergic neurites in the irides of newborn and young rats. Levocarnitine acetyl 20 mg/kg body weight was administered either subcutaneously to newborn rats for 20 days or dissolved in drinking water to young rats for 90 days. Treatment with levocarnitine acetyl promoted neurite outgrowth following axotomy in both groups, thus demonstrating a stimulatory role of the substance in nerve regeneration of the peripheral nervous system. The results further confirm that levocarnitine acetyl is endowed with therapeutical efficacy in peripheral neuropathies.

The effect of adrenal gland hormones on brain NGF-producing cells and on NGF target cells was studied in young adult rats. The results showed that adrenalectomy causes a decrease in the NGF level in the hippocampus and of choline acetyltransferase in the septum. These studies suggest that adrenal gland hormones are involved in the regulation of NGF in specific brain structures.

Concomitatn daily treatment of rats immediately after birth with NGF and 6-OHDA for a period of 2-4 weeks, results in a volume increase of sympathetic ganglia of thirty times that of controls and 2.3 that of NGF treated littermates, at three weeks of age. Studies at the light, fluorescent and electron-microscope, showed that this overall enlargement is due to increase in size and number of sympathetic neurons and, to an even higher extent, to profuse production and branching of collaterals from postganglionic adrenergic nerve fibers. These axonal collaterals find accomodation inside the ganglia where they displace nerve cells and build a thick fibrillar capsule around the same ganglia. The survival in excellent conditions of sympathetic nerve cells treated with NGF but prevented by 6-OHDA from establishing anatomical and functional connections with their end organs, suggests that the growth factor find access to its target cells through the plasms membrane which envelops the cell perikarya. The extraordinary production of collaterals by chemically axotomized sympathetic fibers, brings to light growth potentialities of these fibers which materialize only upon disconnection of their endings from peripheral tissues. These results uncover a new facet of the interaction between nerve fibers and innervated tissues.

Objectives. The aim of our study was to investigate the role of cholecystokinin-8 (CCK-8), which is able to induce the synthesis of nerve growth factor (NGF), in the joint inflammation of carrageenan-injected rats. Methods. Adult rats were injected in the ankle joint with carrageenan, with or without CCK-8 or a CCK receptor antagonist ( proglumide), and tissue swelling, NGF levels and NGF mRNA expression were assessed. Results. Expression of NGF and NGF mRNA increased transiently after carrageenan injection. This effect was not altered by CCK-8 injection but was inhibited by the CCK receptor antagonist. The decrease in NGF level after treatment with the antagonist was concurrent with an increase in paw swelling. Conclusions. The results demonstrate that, whereas CCK-8 has no anti-inflammatory action in carrageenan-injected animals, proglumide induces a worsening of inflammation and reduces the expression of both NGF and NGF mRNA in inflamed ankle joints. Our data point to a regulatory action of CCK-8 on NGF synthesis during acute synovitis and suggest a role for NGF in the healing phase of inflammation.