Brain multiplicity

Carmustine is a bicyclohexylnitrosourea (BCNU, Fig. 3) with broad spectrum of antineoplastic activity (e.g., lymphomas, multiple myeloma, sarcomas, brain tumors, gastrointestinal tumors, melanomas). At doses of 80-200 mg/m2 it is given i.v. at 6 week s intervals. 

Human GAL1 receptor mRNA has been detected in multiple cell and tissue samples including Bowes melanoma cells, brain, gastrointestinal tract (from esophagus to rectum), heart, prostate, and testes. Rat GAL1 mRNA was detected in olfactory regions, many hypothalamic nuclei (including supraoptic nucleus),... 

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Cheeran MC, Hu S, Sheng WS, Rashid A, Peterson PK, Lokensgard JR (2005) Differential responses of human brain cells to West Nile virus infection. J Neurovirol 11 512-524 Cudrici C, Ito T, Zafranskaia E, Niculescu F, Mullen KM, Vlaicu S, Judge SI, Calabresi PA, Rus H (2007) Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis. Exp Mol Pathol 83 198-206... 

Kmmbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E (2006) Chemokines in multiple sclerosis CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129 200-211... 

McCandless EE, Wang Q, Woerner BM, Harper JM, Klein RS (2006) CXCL12 Umits inflammation by localizing mononuclear infiltrates to the perivascular space during experimental autoimmune encephalomyelitis. J Immunol 177 8053-8064 McCandless EE, Piccio L, Woerner BM, Schmidt RE, Rubin JB, Cross AH, Klein RS (2008a) Pathologic expression of CXCL12 at the blood brain barrier correlates with severity of multiple sclerosis. Am J Pathol... 

McCandless EE, Budde M, Lees JR, Dorsey D, Lyng E, Klein RS (2009) IL-IR signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyehtis. J Immunol 183(l) 613-620 McEarland HE, Martin R (2007) Multiple sclerosis a complicated picture of autoimmunity. Nat Immunol 8 913-919... 

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