Biomedical subjects

Gerald Wolf

Publications and source records attributed to Gerald Wolf.

At least 19 recordsLinked to original sources

PubMed2003

A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk.

A common 936 C/T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels. In our case-control study, we investigated the role of this polymorphism for breast cancer risk. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29.4%) than among patients (17.6%; p = 0.000014). The odds ratio for carriers of a 936T-allele for breast cancer was 0.51 (95% confidence interval 0.38-0.70). Additionally, VEGF plasma levels were determined in 21 nonsmoking post-menopausal controls; carriers of a 936T allele had significantly lower levels (median 23 pg/ml; range 6-50 pg/ml) than noncarriers (37; 21-387; p = 0.034). We conclude that carriers of a VEGF 936T-allele are at decreased risk for breast cancer, this, however, requiring further confirmation in a larger study.

Adult↗

PubMed2003

Immunocytochemical distribution of nitric oxide synthase in the human seminal vesicle: a light and electron microscopical study.

Although nitric oxide (NO) has been proven to be one of the most important non-adrenergic, non-cholinergic mediators in the control of human reproductive tract organs, to date information on the significance of NO-mediated signal transduction in the control of human seminal vesicle (SV) function is still sparse.()Recent investigations have underlined the significance of NO in the maintenance of sperm capacitation and viscosity of the seminal plasma as well as in the control of mammalian seminal vesicle smooth muscle tone. In order to further investigate the functional impact of NO on the regulation of normal SV function, we examined the distribution of NADPH-diaphorase (NADPH-d), endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) in the cellular anatomy of human SV by means of light and electron microscopical immunocytochemistry (LM, EM) in combination with the tyramide signal amplification technique. Human SV were obtained from 15 patients who had undergone surgery for pelvic malignancies (carcinoma of the prostate or urinary bladder). SV specimens were fixed, sectioned and examined by LM and EM for the presence of NAPDH-d, eNOS and nNOS using specific antibodies and advanced staining procedures. LM revealed a dense NADPH-d reaction in glandular epithelial structures, whereas no substantial labeling was detected in the fibromuscular stroma. EM showed that the NADPH-d reaction product was abundantly detectable attached to membranes of the endoplasmic reticulum, mitochondria and the nuclei of glandular epithelial cells. nNOS staining was found in nerve fibers branching within the SV tissue. eNOS staining was present in small vessels but was only observed to a minor degree in glandular and subglandular structures and the smooth muscle stroma. Our results support the hypothesis that human SV is a site of NO production. The distribution of NADPH-d may give rise to the speculation that NO is mainly involved in the regulation of SV secretory activity. The sparse correlation between NADPH-d-, eNOS- and nNOS-staining might hint at the existence of a previously unidentified NOS isoform in human SV.

Adult↗

PubMed2003

Endolacrimal KTP laser-assisted dacryocystorhinostomy.

OBJECTIVE: To describe our experience with potassium-titanyl-phosphate (KTP) laser-assisted dacryocystorhinostomy, controlled via endolacrimal and endonasal endoscopy. The development of miniendoscopes enables endoscopy of the lacrimal drainage system via the lacrimal puncta to visualize the exact site of a stenosis. DESIGN: A case series of 78 patients, with 1-year postoperative follow-up. SETTINGS: A university medical center. PATIENTS: Consecutive sample of 78 adult patients who required surgery for dacryostenosis. INTERVENTION: Endolacrimal use of a KTP laser to perform a bony osteotomy of the lacrimal sac into the nasal cavity. The position for the perforation was controlled by endonasal endoscopy. The procedure was performed under either general or local anesthesia. RESULTS: One year after surgery, 65 (83%) of the 78 patients were free of symptoms. Seven patients experienced intermittent tearing, and 6 had revision surgery because of restenosis. CONCLUSIONS: The success rate of 83% achieved with KTP laser-assisted dacryocystorhinostomy, using miniendoscopes for lacrimal endoscopy to visualize the exact site of obstruction, is better compared with that of prior studies without the use of miniendoscopes (with success rates of 47%-85%). The advantages of this technique are that it is a minimally invasive procedure, requires a short operating time, and avoids use of an external incision.

Dacryocystitis↗

PubMed2003

Bio-compatibility of type I/III collagen matrix for peripheral nerve reconstruction.

Nerve gaps are usually bridged by autografts. With improving technical methods biocompatible conduits may become an alternative graft to reconstruct nerves. Non-neural conduits fail to support regeneration over larger gaps due to lacking viable Schwann cells. Thus, tissue engineering of nerves is focusing on implantation of viable Schwann cells into suitable scaffolds. In this study, we tested collagen type I/III tubes as a potential nerve guiding matrix. Revascularization, foreign body reaction, biodegradation and Schwann cell settlement were evaluated by immunocytochemistry, light, fluorescence and scanning electron microscopy, after different implantation times. The conduits were completely revascularized between day 5 and 7 post-operatively and well integrated into the host tissue. Host response was characterized by a moderate invasion of ED1/ED2-positive macrophages. Biodegradation of the tubes was slowly enough to maintain a stable support structure for extended regeneration processes. Implanted Schwann cells adhered, survived and proliferated on the inner surface of the conduits and were able to form nerve guiding columns of Büngner. From this results, we conclude that collagen-type I/III can serve as template to design "living" nerve conduits, which may be able to ensure nerve regeneration through extended nerve gaps.

Biocompatible Materials↗

PubMed2003

Citrulline immunohistochemistry may not necessarily identify nitric oxide synthase activity: the pitfall of peptidylarginine deiminase.

Nitric oxide synthase (NOS) converts L-arginine as a substrate to form nitric oxide and the "by-product" citrulline. To characterize NOS activity in the nervous tissue at the single-cell level, citrulline immunostaining is considered to be a suitable means of working on the principle that in brain tissue, due to the incomplete urea cycle, citrulline is produced exclusively by NOS. This assumption is correct for free citrulline but it does not consider the conversion of arginine to citrulline residues of proteins by the calcium-dependent peptidylarginine deiminase (PAD). Using a polyclonal antiserum against citrulline we observed in cerebellar cell cultures immunopositivity in a few, mostly NOS-positive, neurons, in activated microglia, and in oligodendroglia (which under control conditions are in doubt to be able to express NOS), but not in astroglia. Treatment with the excitotoxin kainate substantially enhanced the staining intensity for citrulline in neurons and glial cells. To distinguish between free (NOS-related) and protein-bound (PAD-related) citrulline we blocked NOS activity by 7-nitroindazole or L-N5-(1-iminoethyl)lysine. The results provide evidence that citrulline immunolabeling results partly from PAD-mediated protein citrullination, enhanced pathophysiologically under stimulated conditions by exposure to kainate. Our immunocytochemical observations were corroborated by Western blot analysis showing several bands of citrulline-positive proteins, whose number and staining intensity depended on kainate treatment and calcium ions.

Animals↗

PubMed2003

Cytosolic and mitochondrial glutathione in microglial cells are differentially affected by oxidative/nitrosative stress.

Glutathione (GSH), the major cellular protectant against reactive oxygen and nitrogen species, is compartmentalized in a cytosolic (c) and a mitochondrial (mt) pool. We investigated how c-GSH and mt-GSH are differentially affected by endogenously produced nitric oxide (NO). Microglial cell line (N9) cultures were immunostimulated with lipopolysaccharide/interferon-gamma to elicit the inducible isoform of NO synthase (iNOS). Despite a significant reduction in total GSH, the mt-GSH remained nearly unaffected by iNOS-mediated NO production. To investigate possible consequences of GSH depletion on the mitochondrial membrane potential, we used buthionine sulfoximine (BSO) to reduce separately the c-GSH, whereas ethacrynic acid (EA) was applied to deplete both mt-GSH and c-GSH. The mitochondrial membrane potential was more vulnerable to NO exposure in EA-pretreated cultures than in BSO-pretreated cultures, indicated by a potentiated release of tetramethylrhodamine from mitochondria into the cytosol. To relate the EA-mediated decrease in mitochondrial membrane potential to the oxidant buildup after GSH depletion, we loaded the cells with the oxidant-sensitive fluorochrome 2',7'-dihydrodichlorofluorescein (DCF) diacetate. EA treatment caused an increase in DCF fluorescence over time that was potentiated when the iNOS expression was stimulated. Inhibition of NO production abolished this effect. We conclude that endogenous NO production in microglial cells does not compromise the mt-GSH pool which, in turn, might explain the ability of these cells to combat high-output NO production.

Buthionine Sulfoximine↗

PubMed2003

Gliap--a novel untypical L-asparaginase localized to rat brain astrocytes.

L-asparaginases catalyse the formation of the neuroactive amino acid L-aspartate by deamination of asparagine. The major pathophysiological significance of L-asparaginase activity is in its clinical use for the treatment of acute lymphatic leukaemia and neoplasias that require asparagine and obtain it from circulating pools. Here we report the identification and characterization of Gliap, a cytosolic L-asparaginase, which is the founding member of a new group of L-asparaginases in mammalia. Structural modelling suggests that Gliap is an atypical mammalian type-I asparaginase inasmuch as it harbours the active centre of a type-I glycosylasparaginase but, like plant-type asparaginases, lacks their auto-proteolytic site and, in addition, exhibits significant type-II L-asparaginase enzymatic activity. Moreover, in contrast to glycosylasparaginases Gliap is enriched in the cytosolic fraction and not in lysosomes. The protein is particularly abundant in liver, testis and brain. In brain Gliap is exclusively expressed in astrocytes and prominently present in structures reminiscent of glial endfeet. These data suggest that Gliap is involved in astroglial production of the neuroactive amino acid L-aspartate.

Amino Acid Sequence↗

PubMed2002

Host responses after acellular muscle basal lamina allografting used as a matrix for tissue engineered nerve grafts1.

BACKGROUND: A nerve gap must be bridged by autologous nerve grafts that serve as scaffold and consist of viable Schwann cells that promote regeneration. Owing to the necessary immunosuppression, nerve allografts remain limited to special cases. Alternatively, tissue engineering of peripheral nerves focuses on the implantation of cultured Schwann cells into suitable scaffolds. We established grafts from Schwann cells and basal lamina from acellular muscles. These grafts offer a regeneration that is comparable to autologous nerve grafts. METHODS: Using a rat model (DALEW.1W strain), the present study evaluates the host response to acellular muscle allografts by assessing cellular reaction major histocompatability (MHC) class I and II, lymphocytes, macrophages. The results were compared to untreated muscle allografts. RESULTS: Macroscopically, the untreated muscles showed a strong inflammatory reaction as a sign of rejection, whereas the acellular muscle offered only minor reactions in the periphery of the graft. Expression of MHC I and II and invasion of CD4/CD8 positive cells and macrophages was pronounced after grafting the untreated muscles. Only a moderate reaction was noted for these parameters after acellular grafting. CONCLUSIONS: The acellular muscle graft is not completely free of cellular response; however the reaction is considered to be moderate and is located only in the periphery. To date, synthetic scaffolds that represent endoneurial tube-like structures and allow sufficient adhesion of Schwann cells and axonal regeneration are not available. The decreased response to acellular muscle allografts offers at least a basis for further experiments.

Animals↗

PubMed2002

NOS-mediated differences in peripheral nerve graft revascularization and regeneration.

Dependence of peripheral nerve revascularization on endogenous nitric oxide supply and consequences for nerve regeneration were investigated using a sciatic nerve graft model in mice lacking one of the nitric oxide synthase (NOS) isoforms. Wild type mice and mice lacking neuronal or inducible NOS exhibited similar revascularization patterns. Perfusion was consistently established 3 days after nerve reconstruction. Mice lacking endothelial NOS showed a delay in revascularization of about 2 days. The regeneration outcome did not reflect these differences. In mice lacking endothelial NOS, axon counts, myelination and recovery of sensory and motor function were comparable to wild type mice, whereas in mice lacking neuronal or inducible NOS a disturbed regeneration was found. Present results demonstrate, that the disturbance of nerve revascularization as result of reduced endothelial NOS-mediated NO supply can be tolerated, possibly by enhanced phagocytic capacity of Schwann cells and/or resident endoneurial macrophages.

Animals↗

PubMed2002

Release patterns of excitatory and inhibitory amino acids within the hypothalamic supraoptic nucleus in response to direct nitric oxide administration during forced swimming in rats.

The effect of direct intrahypothalamic nitric oxide (NO) administration on the release of selected amino acids in the hypothalamic supraoptic nucleus (SON) with and without concomitant forced swimming was investigated. Adult male Wistar rats were chronically fitted with U-shaped microdialysis probes in the SON and forced to swim for 10-min in 20-degree C warm water. Thirty-min microdialysis samples were collected before, during and after the forced swimming period while NO was administered into the SON via microdialysis. The results show that NO administration in combination with forced swimming affects the release of aspartate, glutamate, taurine, and gamma aminobutyric acid (GABA) in different patterns. Whereas the release of the excitatory amino acids aspartate and glutamate was triggered only during NO administration and forced swimming, the inhibitory amino acids GABA and taurine were found in the extracellular fluid in increased concentrations also after the treatment. These data indicate that NO administration differently affects the release of excitatory and inhibitory amino acids within the SON. Thus, SON neurons which contain high concentrations of neuronal NO synthase, might contribute to the regulation of their own secretory activity by releasing NO that controls the orchestrated release of excitatory and inhibitory amino acids from axon terminals of afferences and interneurons as well as release from glial cells.

Animals↗

PubMed2002

Differences in peripheral nerve degeneration/regeneration between wild-type and neuronal nitric oxide synthase knockout mice.

Nitric oxide (NO), a unique biological messenger molecule, is synthesized by three isoforms of the enzyme NO synthase (NOS) and diffuses from the site of production across cellular membranes. A postulated role for NO in degeneration and regeneration of peripheral nerves has been explored in a sciatic nerve model comparing wild-type mice and mice lacking neuronal NOS after transection and microsurgical repair. In NOS knockout mice, regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). In the regenerated nerve, pruning of uncontrolled sprouts was disturbed, leading to an enhanced number of axons, whereas remyelination seemed to be less affected. Delayed regeneration was associated with a delayed recovery of sensor and motor function. In such a context, possible NO targets are neurofilaments and myelin sheaths of the interrupted axon, filopodia of the growth cone, newly formed neuromuscular endplates, and Schwann cells in the distal nerve stump. The results presented suggest that 1) local release of NO following peripheral nerve injury is a crucial factor in degeneration/regeneration, 2) success of fiber regeneration in the peripheral nervous system depends on a regular WD, and 3) manipulation of NO supply may offer interesting therapeutic options for treatment of peripheral nerve lesions.

Animals↗

PubMed2002

[SAPHO syndrome: case report of an 18-year-old man and review of the literature].

We report about an 18-year-old man, suffering from acne on his face and trunk and complaining about indefinite bone pains--without any trauma. SAPHO-syndrome was diagnosed which consists of synovitis, acne, pustulosis, hyperostosis and osteitis. Five types of this syndrome can be differentiated: spondarthritis hyperostotica pustulo-psoriatica, chronic recurrent multifocal osteomyelitis, inflammatory chest wall syndrome, isolated sternocostoclavicular hyperostosis, and the combined form of acne-associated spondarthritis and chronic recurrent osteomyelitis. Although the sapho-syndrome is very rare, it should be considered a possible diagnosis in the case of indefinite bone pains in combination with acne, pustulosis and hyperostosis.

Acne Vulgaris↗

PubMed2002

Oxidative stress in glial cultures: detection by DAF-2 fluorescence used as a tool to measure peroxynitrite rather than nitric oxide.

4,5-diaminofluorescein diacetate (DAF-2DA) is widely used as a fluorescent probe to detect endogenously produced nitric oxide (NO). Recent reports that refer to the high sensitivity of DAF-2 toward NO prompted us to test its efficiency and specificity in a mixed murine primary glial culture model, in which the NO-synthesizing enzyme inducible nitric oxide synthase (iNOS) is expressed by stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Cultures were loaded with DAF-2DA and the fluorescence was measured using confocal microscopy. NO production in the cultures was determined using the ozone/chemiluminescence technique. Due to the extremely high photosensitivity of DAF-2, low laser intensities were used to avoid artifacts. No difference in DAF-2 fluorescence was observed in NO-producing cultures compared to control cultures, whereas the NO/peroxynitrite-sensitive dye 2,7-dihydrodichlorofluorescein (DCF) showed a significant fluorescence increase specifically in microglia cells. A detectable gain in fluorescence was seen when NO-containing buffer was added to the DAF-2DA-loaded cells with a minimum NO concentration at 7.7 microM. An additional gain of DAF-2 fluorescence was obtained when the cells were depleted of glutathione (GSH) with L-buthionine S,R-sulfoximine (BSO). Hence, we monitored the change in DAF-2 fluorescence intensity in the presence of NO and O(-*)(2) in a cell-free solution. The fluorescence due to NO was indeed larger when O(-*)(2) was added, implying a higher sensitivity of DAF-2 for peroxynitrite. Nevertheless, our results also indicate that measurement of DCF fluorescence is a better tool for monitoring intracellular changes in the levels of NO and/or peroxynitrite than DAF-2.

Animals↗

PubMed2002

Differential distribution of spermidine/spermine-like immunoreactivity in neurons of the adult rat brain.

The polyamines spermidine and spermine are small, widely distributed polycations. In the brain, they confer rectification properties upon inwardly rectifying potassium channels and Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptors and also modify functional properties of N-methyl-D-aspartate receptors. Therefore, functional roles of spermidine/spermine in the adult brain will depend on the colocalization of the spermidine/spermine-sensitive receptors/channels and the polyamines either in the same or in closely associated cell types. We previously immunocytochemically demonstrated a prominent localization of spermidine/spermine in glial cells, especially astrocytes (Laube and Veh [ 1997] Glia 19:171-179). In contrast to the commonly accepted assumption of a ubiquitous distribution of polyamines in various cell types, in neurons of the rat brain, we detected a highly diverse spermidine/spermine-like immunoreactivity. The immunoreactivity in neurons and neuropil throughout the rat brain is listed according to intensity in arbitrary groups. The strongest neuronal staining was observed in the hypothalamic paraventricular, supraoptic, and accessory neurosecretory nuclei. Strong cytoplasmic staining was also evident in some motor and somatosensory areas such as the Me5 nucleus of the mesencephalic trigeminal tract, the nucleus ruber, and the large motor neurons of the spinal cord ventral horn. In contrast, in most cortical and hippocampal regions spermidine/spermine-like immunoreactivity in neurons was relatively weak, whereas in these areas, the labeling pattern was dominated by a diffuse neuropil labeling. In addition to spermidine/spermine immunocytochemistry, ornithine decarboxylase labeling was performed and the resulting labeling patterns were compared. The prominent localization of spermidine/spermine in neurosecretory neurons might point to a functional role different from channel/receptor modification. In these neurons, polyamines might be involved in secretory processes.

Animals↗

PubMed2002

Life imaging of peroxynitrite in rat microglial and astroglial cells: Role of superoxide and antioxidants.

Free radicals, such as superoxide and nitric oxide, are known to play a role in a number of inflammatory and degenerative brain diseases, in which resident microglia upregulate the inducible nitric oxide synthase (iNOS) and thus produce large amounts of nitric oxide. Simultaneously, microglia generate superoxide mainly via NADPH-oxidase, which reacts at a diffusion-limited rate with nitric oxide to form the powerful oxidant peroxynitrite. We used mixed astroglial/microglial cultures to study the effects of iNOS induction by lipopolysaccharide and interferon-gamma on free radical formation. Using the fluorogenic compound 2,7-dihydrodichlorofluorescein diacetate, we monitored cellular peroxynitrite formation by confocal laser microscopy. Peroxynitrite formation in continuously nitric oxide-producing microglial cells was rather limited. However, activation of the superoxide-generating enzyme NADPH-oxidase dramatically increased DCF fluorescence within a few minutes. We conclude that superoxide is the limiting factor for peroxynitrite formation. Since the formation and oxidant activity of peroxynitrite depends strongly on the availability of cellular antioxidants, we investigated the capacity of several compounds to influence peroxynitrite formation. Among the substances under investigation in this study, glutathione and the synthetic compound ebselen had a major effect on preventing peroxynitrite formation, whereas ascorbate failed to decrease peroxynitrite levels.

Animals↗

PubMed2002

Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells.

The bridging of nerve gaps is still one of the major problems in peripheral nerve surgery. The present experiment describes our attempt to engineer different biologic nerve grafts in a rat sciatic nerve model: cultured isogenic Schwann cells were implanted into 2-cm autologous acellular nerve grafts or autologous predegenerated nerve grafts. Autologous nerve grafts and predegenerated or acellular nerve grafts without implanted Schwann cells served as controls. The regenerated nerves were assessed histologically and morphometrically after 6 weeks. Predegenerated grafts showed results superior in regard to axon count and histologic appearance in comparison to standard grafts and acellular grafts. The acellular nerve grafts showed the worst histologic picture, but axon counts were in the range of standard grafts. The implantation of Schwann cells did not yield significant improvements in any group. In conclusion, the status of activation of Schwann cells and the stadium of Wallerian degeneration in a nerve graft might be key factors for regeneration, rather than total number of Schwann cells. Predegenerated nerve grafts are therefore superior to standard grafts in the rat model. Acellular grafts are able to bridge nerve gaps of up to 2 cm in the rat model, but even the addition of cultivated Schwann cells did not lead to results as good as in the group with autologous nerve grafts.

Animals↗

PubMed2002

Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts.

To overcome the problems of limited donor nerves for nerve reconstruction, we established nerve grafts made from cultured Schwann cells and basal lamina from acellular muscle and used them to bridge a 2-cm defect of the rat sciatic nerve. Due to their basal lamina and to viable Schwann cells, these grafts allow regeneration that is comparable to autologous nerve grafts. In order to enhance regeneration, insulin-like growth factor (IGF-I) was locally applied via osmotic pumps. Autologous nerve grafts with and without IGF-I served as controls. Muscle weight ratio was significantly increased in the autograft group treated with IGF-I compared to the group with no treatment; no effect was evident in the tissue-engineered grafts. Autografts with IGF-I application revealed a significantly increased axon count and an improved g-ratio as indicator for "maturity" of axons compared to autografts without IGF-I. IGF-I application to the engineered grafts resulted in a decreased axon count compared to grafts without IGF-I. The g-ratio, however, revealed no significant difference between the groups. Local administration of IGF-I improves axonal regeneration in regular nerve grafts, but not in tissue-engineered grafts. Seemingly, in these grafts the interactive feedback mechanisms of neuron, glial cell, and extracellular matrix are not established, and IGF-I cannot exert its action as a pleiotrophic signal.

Animals↗

PubMed2002

Nitric oxide affects the phosphorylation state of microtubule-associated protein 2 (MAP-2) and neurofilament: an immunocytochemical study in the brain of rats and neuronal nitric oxide synthase (nNOS)-knockouts.

Alterations in function and specific cellular location of cytoskeletal elements are characterized by changes in their phosphorylation state. On this background we studied immunocytochemically the distribution pattern of neurofilament (NF) in its phosphorylated (P-NF) and nonphosphorylated (NP-NF) form and of microtubule-associated protein-2 (MAP-2) in the rat and mouse brain. Neurons that are strongly positive for neuronal nitric oxide synthase (nNOS)-immunoreactivity (IR) showed, interestingly, neither P-NF- nor MAP-2-IR. In contrast, nNOS-negative neuronal cell elements exhibited an intense IR and specific location for both antigens throughout the brain. As a model we chose the dorsolateral tegmental nucleus (LDT) of knockout (nNOS(-/-)) mice in which the main splice isoform nNOSalpha is lacking, but a low nNOS-activity persists, apparently due to the splice isoforms nNOSbeta and gamma. The principal neurons of such nNOS(-/-)-mice, which are equivalent to the nNOS-containing neurons in the LDT of wild-type mice exhibited a decreased nitrotyrosine-IR and an increased phosphotyrosine-IR if compared to those of wild-type mice. The same neurons failed to show NF-IR and MAP-2-IR, though. When the residual nNOS activity in nNOS(-/-)-mice was inhibited by treatment with N-omega-nitro-L-arginine methyl ester (L-NAME) the principal neurons displayed a moderate MAP-2 and NF-staining. NO and NO-derived oxygen species are suggested to modulate the balance between the activities of kinases and phosphatases, thus changing phosphorylation levels for NF, MAP-2, and, possibly, other proteins in neurons and adjacent cell elements.

Animals↗