**7. References**


Synthetic Glucocorticoids Modulate Function of Neural

Vol.26, No.6, Jun 2007, pp. (935-40).

Vol.14, No.6, Jun 1989, pp. (585-7).

(2529-34).

2001, pp. (57-69).

*Ther*, Vol.24, No.5, Sep-Oct 2007, pp. (1052-60).

Cells: Implications in Autoimmune Neurological Disorders 333

Gonzalez-Castaneda, R.E., Castellanos-Alvarado, E.A., Flores-Marquez, M.R., et al. (2007).

Gonzalez-Perez, O., & Alvarez-Buylla, A. (2011). Oligodendrogenesis in the subventricular zone and the role of epidermal growth factor. *Brain Res Rev*, Jan 12 2011, pp. Gonzalez-Perez, O., Luquin, S., Garcia-Estrada, J., et al. (2007). Deflazacort: a glucocorticoid

Gonzalez-Perez, O., Ramos-Remus, C., Garcia-Estrada, J., et al. (2001). Prednisone induces

Hansson, E. (1989). Regulation of glutamine synthetase synthesis and activity by

Hara, K., Watanabe, K., Miyazaki, S., et al. (1981). Apparent brain atrophy and subdural hematoma following ACTH therapy. *Brain Dev*, Vol.3, No.1, 1981, pp. (45-9). Hauser, J., Dettling-Artho, A., Pilloud, S., et al. (2007). Effects of prenatal dexamethasone

marmoset monkey. *Endocrinology*, Vol.148, No.4, Apr 2007, pp. (1813-22). Hauser, J., Feldon, J., & Pryce, C.R. (2006). Prenatal dexamethasone exposure, postnatal

Haynes, L.E., Griffiths, M.R., Hyde, R.E., et al. (2001). Dexamethasone induces limited

Hill, J.E., Makky, K., Shrestha, L., et al. (2010). Natural and synthetic corticosteroids inhibit uptake(2)-mediated transport in CNS neurons. *Physiol Behav*, Nov 21 2010, pp. Hoppmann, J., Perwitz, N., Meier, B., et al. (2010). The balance between gluco- and

Hu, W., Zhang, M., Czeh, B., et al. (2010). Stress impairs GABAergic network function in the

Huang, W.L., Harper, C.G., Evans, S.F., et al. (2001a). Repeated prenatal corticosteroid

Huang, W.L., Harper, C.G., Evans, S.F., et al. (2001b). Repeated prenatal corticosteroid

Ihrie, R.A., & Alvarez-Buylla, A. (2008). Cells in the astroglial lineage are neural stem cells.

Ji, B., Li, M., Budel, S., et al. (2005). Effect of combined treatment with methylprednisolone

*Neuropsychopharmacology*, Vol.35, No.8, Jul 2010, pp. (1693-707).

sheep. *Int J Dev Neurosci*, Vol.19, No.5, Aug 2001a, pp. (487-93).

rats. *Behav Brain Res*, Vol.175, No.1, Nov 25 2006, pp. (51-61).

*Endocrinol*, Vol.204, No.2, Feb 2010, pp. (153-64).

*Neurosci*, Vol.19, No.4, Jul 2001b, pp. (415-25).

No.3, Aug 2005, pp. (587-94).

*Cell Tissue Res*, Vol.331, No.1, Jan 2008, pp. (179-91).

Deflazacort induced stronger immunosuppression than expected. *Clin Rheumatol*,

with few metabolic adverse effects but important immunosuppressive activity. *Adv* 

anxiety and glial cerebral changes in rats. *J Rheumatol*, Vol.28, No.11, Nov 2001, pp.

glucocorticoids and adrenoceptor activation in astroglial cells. *Neurochem Res*,

treatment on postnatal physical, endocrine, and social development in the common

development, and adulthood prepulse inhibition and latent inhibition in Wistar

apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders. *Neuroscience*, Vol.104, No.1,

mineralo-corticoid action critically determines inflammatory adipocyte responses. *J* 

hippocampus by activating nongenomic glucocorticoid receptors and affecting the integrity of the parvalbumin-expressing neuronal network.

administration delays astrocyte and capillary tight junction maturation in fetal

administration delays myelination of the corpus callosum in fetal sheep. *Int J Dev* 

and soluble Nogo-66 receptor after rat spinal cord injury. *Eur J Neurosci*, Vol.22,


Bender, B.G., Lerner, J.A., & Poland, J.E. (1991). Association between corticosteroids and

Bentson, J., Reza, M., Winter, J., et al. (1978). Steroids and apparent cerebral atrophy on

Black, H.E. (1988). The effects of steroids upon the gastrointestinal tract. *Toxicol Pathol*,

Bohn, M.C., Howard, E., Vielkind, U., et al. (1991). Glial cells express both mineralocorticoid

Bridges, N., Slais, K., & Sykova, E. (2008). The effects of chronic corticosterone on

Buckingham, J.C. (2006). Glucocorticoids: exemplars of multi-tasking. *Br J Pharmacol*, Vol.147

Crossin, K.L., Tai, M.H., Krushel, L.A., et al. (1997). Glucocorticoid receptor pathways are

Cucullo, L., Hallene, K., Dini, G., et al. (2004). Glycerophosphoinositol and dexamethasone

Chen, X., Hu, X., Zou, Y., et al. (2009). Combined treatment with minocycline and

de Kloet, E.R. (2003). Hormones, brain and stress. *Endocr Regul*, Vol.37, No.2, Jun 2003, pp.

de Kloet, E.R., Oitzl, M.S., & Joels, M. (1999). Stress and cognition: are corticosteroids good

De Kloet, E.R., Vreugdenhil, E., Oitzl, M.S., et al. (1998). Brain corticosteroid receptor balance in health and disease. *Endocr Rev*, Vol.19, No.3, Jun 1998, pp. (269-301). de Sousa, N.G., Santa-Marta, C., & Morais-Almeida, M. (2010). Systemic corticosteroid

Emgard, M., Paradisi, M., Pirondi, S., et al. (2007). Prenatal glucocorticoid exposure affects

Fietta, P., Fietta, P., & Delsante, G. (2009). Central nervous system effects of natural and

Glybina, I.V., Kennedy, A., Ashton, P., et al. (2010). Intravitreous delivery of the

rats. *Invest Ophthalmol Vis Sci*, Vol.51, No.8, Aug 2010, pp. (4243-52). Gomez, C.M., Higuero, N.C., Moral de Gregorio, A., et al. (2002). Urticaria-angioedema by

deflazacort. *Allergy*, Vol.57, No.4, Apr 2002, pp. (370-1).

*Neurobiol Exp (Wars)*, Vol.68, No.2, 2008, pp. (131-8).

barrier. *Brain Res*, Vol.997, No.2, Feb 6 2004, pp. (147-51).

mice. *J Neuroimmunol*, Vol.210, No.1-2, May 29 2009, pp. (22-9).

or bad guys? *Trends Neurosci*, Vol.22, No.10, Oct 1999, pp. (422-6).

May 1991, pp. (414-9).

Vol.16, No.2, 1988, pp. (213-22).

Suppl 1, Jan 2006, pp. (S258-68).

Vol.94, No.6, Mar 18 1997, pp. (2687-92).

23).

(105-11).

(51-68).

(529-32).

22).

2007, pp. (112-21).

psychologic change in hospitalized asthmatic children. *Ann Allergy*, Vol.66, No.5,

computed tomography scans. *J Comput Assist Tomogr*, Vol.2, No.1, Jan 1978, pp. (16-

and glucocorticoid receptors. *J Steroid Biochem Mol Biol*, Vol.40, No.1-3, 1991, pp.

hippocampal astrocyte numbers: a comparison of male and female Wistar rats. *Acta* 

involved in the inhibition of astrocyte proliferation. *Proc Natl Acad Sci U S A*,

improve transendothelial electrical resistance in an in vitro study of the blood-brain

prednisone attenuates experimental autoimmune encephalomyelitis in C57 BL/6

hypersensitivity in children. *J Investig Allergol Clin Immunol*, Vol.20, No.6, 2010, pp.

learning and vulnerability of cholinergic neurons. *Neurobiol Aging*, Vol.28, No.1, Jan

synthetic glucocorticoids. *Psychiatry Clin Neurosci*, Vol.63, No.5, Oct 2009, pp. (613-

corticosteroid fluocinolone acetonide attenuates retinal degeneration in S334ter-4


Synthetic Glucocorticoids Modulate Function of Neural

Vol.26, No.1, Mar 1999, pp. (12-21).

*Clin Immunol*, Vol.127, No.2, Feb 2011, pp. (524-8).

*Investig Med*, Vol.50, No.6, Nov 2002, pp. (458-64).

Vol.136, No.5, May 1995, pp. (2066-73).

No.2, Jan 19 2007, pp. (482-94).

Vol.18, No.1, 2005, pp. (41-78).

No.2, Aug 2005, pp. (289-300).

pp. (860-9).

pp. (1719-23).

Toronto.

Cells: Implications in Autoimmune Neurological Disorders 335

Niu, H., Hinkle, D.A., & Wise, P.M. (1997). Dexamethasone regulates basic fibroblast growth

astrocytes. *Brain Res Mol Brain Res*, Vol.51, No.1-2, Nov 1997, pp. (97-105). O'Callaghan, J.P., Brinton, R.E., & McEwen, B.S. (1991). Glucocorticoids regulate the

Pousset, F., Cremona, S., Dantzer, R., et al. (1999). Interleukin-4 and interleukin-10 regulate

Prager, E.M., Brielmaier, J., Bergstrom, H.C., et al. (2010). Localization of mineralocorticoid receptors at mammalian synapses. *PLoS One*, Vol.5, No.12, 2010, pp. (e14344). Rachid, R., Leslie, D., Schneider, L., et al. (2011). Hypersensitivity to systemic

Ramos-Remus, C., Gonzalez-Castaneda, R.E., Gonzalez-Perez, O., et al. (2002). Prednisone

Reagan, L.P., Rosell, D.R., Wood, G.E., et al. (2004). Chronic restraint stress up-regulates

Sabolek, M., Herborg, A., Schwarz, J., et al. (2006). Dexamethasone blocks astroglial

Sandau, U.S., & Handa, R.J. (2007). Glucocorticoids exacerbate hypoxia-induced expression

Schimmer, B.P., & George, S.R. (1998). Adrenocortical steroid hormones. In *Principles of* 

Schmidt, L.A., Fox, N.A., Goldberg, M.C., et al. (1999). Effects of acute prednisone

Silverman, M.N., Pearce, B.D., Biron, C.A., et al. (2005). Immune modulation of the

Spataro, L., Dilgen, J., Retterer, S., et al. (2005). Dexamethasone treatment reduces astroglia

Tegethoff, M., Pryce, C., & Meinlschmidt, G. (2009). Effects of intrauterine exposure to

*Psychoneuroendocrinology*, Vol.24, No.4, May 1999, pp. (461-83).

factor, nerve growth factor and S100beta expression in cultured hippocampal

synthesis of glial fibrillary acidic protein in intact and adrenalectomized rats but do not affect its expression following brain injury. *J Neurochem*, Vol.57, No.3, Sep 1991,

IL1-beta induced mouse primary astrocyte activation: a comparative study. *Glia*,

corticosteroids: an infrequent but potentially life-threatening condition. *J Allergy* 

induces cognitive dysfunction, neuronal degeneration, and reactive gliosis in rats. *J* 

GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptine. *Proc Natl Acad Sci U S A*, Vol.101, No.7, Feb 17 2004, pp. (2179-84). Rozovsky, I., Laping, N.J., Krohn, K., et al. (1995). Transcriptional regulation of glial

fibrillary acidic protein by corticosterone in rat astrocytes in vitro is influenced by the duration of time in culture and by astrocyte-neuron interactions. *Endocrinology*,

differentiation from neural precursor cells. *Neuroreport*, Vol.17, No.16, Nov 6 2006,

of the pro-apoptotic gene Bnip3 in the developing cortex. *Neuroscience*, Vol.144,

*medical pharmacology*, (Kalant, H., et al., Eds.), pp. 634-646. Saunders Elsevier,

administration on memory, attention and emotion in healthy human adults.

hypothalamic-pituitary-adrenal (HPA) axis during viral infection. *Viral Immunol*,

responses to inserted neuroprosthetic devices in rat neocortex. *Exp Neurol*, Vol.194,

synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary-

Keenan, P.A., Jacobson, M.W., Soleymani, R.M., et al. (1996). The effect on memory of chronic prednisone treatment in patients with systemic disease. *Neurology*, Vol.47, No.6, Dec 1996, pp. (1396-402).

Kettenmann, H., & Ransom, B.R. (2005). Neuroglia. Oxford University Press, New York.


Keenan, P.A., Jacobson, M.W., Soleymani, R.M., et al. (1996). The effect on memory of

Krushel, L.A., Tai, M.H., Cunningham, B.A., et al. (1998). Neural cell adhesion molecule (N-

Lambert, K.G., Gerecke, K.M., Quadros, P.S., et al. (2000). Activity-stress increases density of

Liberman, A.C., Castro, C.N., Noguerol, M.A., et al. (2010). Molecular Mechanisms of

Liu, W.L., Lee, Y.H., Tsai, S.Y., et al. (2008). Methylprednisolone inhibits the expression of

Lowenberg, M., Tuynman, J., Bilderbeek, J., et al. (2005). Rapid immunosuppressive effects

Lowenberg, M., Verhaar, A.P., Bilderbeek, J., et al. (2006). Glucocorticoids cause rapid

Marques, A.H., Silverman, M.N., & Sternberg, E.M. (2009). Glucocorticoid dysregulations

McArthur, S., McHale, E., Dalley, J.W., et al. (2005). Altered mesencephalic dopaminergic

McLeod, J.D., & Bolton, C. (1995). Dexamethasone induces an increase in intracellular and

Navarro Llanos, A., Elizalde Eguinoa, J., Boto de los Bueys, B., et al. (1996). [Toxic epidermal

Neigh, G.N., Owens, M.J., Taylor, W.R., et al. (2010). Changes in the vascular area fraction of

adult stress. *J Cereb Blood Flow Metab*, Vol.30, No.6, Jun 2010, pp. (1100-4). Nichols, N.R., Agolley, D., Zieba, M., et al. (2005). Glucocorticoid regulation of glial

exposure. *J Neuroendocrinol*, Vol.17, No.8, Aug 2005, pp. (475-82).

Kettenmann, H., & Ransom, B.R. (2005). Neuroglia. Oxford University Press, New York. King, D.J., Brunton, J., & Barr, R.D. (1988). The influence of corticosteroids on human

No.6, Dec 1996, pp. (1396-402).

1988, pp. (313-5).

2000, pp. (275-84).

pp. (1703-10).

Vol.1179, Oct 2009, pp. (1-18).

*Reviews*, Vol.6, No.4, 2010, pp. (371-380).

astrocytes. *Glia*, Vol.56, No.13, Oct 2008, pp. (1390-400).

FYN. *EMBO Rep*, Vol.7, No.10, Oct 2006, pp. (1023-9).

*Mol Neurobiol*, Vol.15, No.2, Apr 1995, pp. (193-205).

*Brain Res Rev*, Vol.48, No.2, Apr 2005, pp. (287-301).

Vol.106, No.15, Apr 20 1996, pp. (599).

6).

chronic prednisone treatment in patients with systemic disease. *Neurology*, Vol.47,

erythropoiesis. An in vivo study. *Am J Pediatr Hematol Oncol*, Vol.10, No.4, Winter

CAM) domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation. *Proc Natl Acad Sci U S A*, Vol.95, No.5, Mar 3 1998, pp. (2592-

GFAP-immunoreactive astrocytes in the rat hippocampus. *Stress*, Vol.3, No.4, Nov

Glucocorticoids Action: From Basic Research to Clinical. *Current Immunology* 

glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated

of glucocorticoids mediated through Lck and Fyn. *Blood*, Vol.106, No.5, Sep 1 2005,

dissociation of a T-cell-receptor-associated protein complex containing LCK and

and their clinical correlates. From receptors to therapeutics. *Ann N Y Acad Sci*,

populations in adulthood as a consequence of brief perinatal glucocorticoid

membrane-associated lipocortin-1 (annexin-1) in rat astrocyte primary cultures. *Cell* 

necrolysis in a patient treated with high doses of deflazacort]. *Med Clin (Barc)*,

the hippocampus and amygdala are induced by prenatal dexamethasone and/or

responses during hippocampal neurodegeneration and regeneration. *Brain Res* 


adrenal axis function in humans: a systematic review. *Endocr Rev*, Vol.30, No.7, Dec 2009, pp. (753-89).

**17** 

*Greece* 

**Intravenous Immunoglobulins in** 

**and Novel Clinical Applications** 

*Neurological Department, Laiko General Hospital of Athens* 

Konstantina G. Yiannopoulou

**Neurological Diseases: Established** 

Over the last decade, high-dose polyclonal intravenous immunoglobulin (IVIg) is used increasingly in the management of autoimmune conditions of the central and peripheral nervous system. Despite the expanded use of IVIg, the consensus on its optimal use is insufficient. Currently chronic idiopathic demyelinating polyneuropathy (CIDP), Guillain – Barre syndrome (GBS) and multifocal motor neuropathy (MMN) are the three major immune neuropathies, in which the latest evidence strongly supports the use of IVIg as a first-line therapy. In addition to these disorders, there is a rising number of other neurological indications in which IVIg has been used as a therapy, even though the available evidence-based data are relatively sparse and less convincing. Due to increasing costs of this treatment and relative shortage of products, careful selection of patients who

In this paper the current literature on the use of IVIG in treatment of neurological diseases has been reviewed and evidence-based recommendations, as well as less convincing data

Currently CIDP, GBS and MMN are the three major immune neuropathies, in which the latest evidence strongly supports the use of IVIg as a first-line therapy (level A recommendation). However, questions remain regarding the dose, timing and duration of IVIg treatment in these disorders. The efficacy of IVIg has been also proven in some paraneoplastic neuropathies (level B) (European Federation of Neurology Society [EFNS] task force, 2008; Elovaara & Hietaharju, 2010). There are other peripheral neuropathies in which there are reports of the efficacy of IVIg. These include diabetic amyotrophy, vasculitic peripheral neuropathy and painful sensory neuropathy associated with Sjogren's syndrome. The evidence for these conditions has been insufficient to earn a recommendation for the use

GBS is an autoimmune disorder of the peripheral nervous system. The incidence of GBS is approximately two per 100 000/year in adults. It may lead to respiratory failure requiring

will benefit from IVIg is extremely important (Elovaara & Hietaharju, 2010).

and future possibilities for its use in these disorders are presented.

of IVIg from national or international guidelines (Hughes et al, 2009).

**2. IVIg in therapy of autoimmune neuropathies** 

**2.1 Guillan-barre syndrome (GBS)** 

**1. Introduction** 

