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The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice

, : The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. Proceedings of the National Academy of Sciences of the United States of America 102(52): 19045-19050

Neurotrophins (NTs) such as BDNF, NT-3, and NT-4 are important modulators of neuronal function and survival. Their expression in the CNS after various insults is thus of major therapeutic consequence. Glatiramer acetate [(GA) Copaxone], an approved drug for the treatment of multiple sclerosis, has been shown to induce Th2/3 cells that accumulate in the CNS, expressing in situ antiinflammatory cytokines and BDNF. In the present study, we investigated whether s.c. injections of GA, applied at various stages of experimental autoimmune encephalomyelitis, affect the expression of NTs, particularly BDNF, in the brain. In untreated experimental autoimmune encephalomyelitis mice, the expression of NTs was elevated shortly after disease appearance but subsequently declined below that of naive mice. In contrast, GA treatment led to sustained augmentation in the expression of BDNF, NT-3, and NT-4 in various brain regions as demonstrated by histological analysis of immunostained brain sections. GA treatment, even when started 45 days after disease induction, restored the impaired level of NTs to that of healthy mice. BDNF elevation after GA treatment was demonstrated on both protein and mRNA levels. Prominent staining was manifested not only by infiltrating GA-induced T cells, but also by CNS resident cells (neurons and astrocytes), indicative of a bystander therapeutic effect. Of importance, in GA-treated mice, intense BDNIF expression was manifested by neuronal progenitors that migrated into lesions in injured regions. These results indicate that the immunomodulator GA exerts not only an antiinflammatory effect, but also enhances neuroprotection and regeneration of neural elements in the diseased brain.


PMID: 16365293

DOI: 10.1073/pnas.0509438102

Other references

Weiland D.; Mondon C.; Reaven G., 1978: Prolongation of insulin removal by perfused liver from hyper insulinemic rats. Clinical Research 26(2): 133A

Fischer-Colbrie, R.; Wohlfarter, T.; Schmid, K.W.; Grino, M.; Winkler, H., 1989: Dexamethasone induces an increased biosynthesis of chromogranin A in rat pituitary gland. The influence of dexamethasone on the regulation of the biosynthesis of chromogranins A and B, two proteins originally described in adrenal chromaffin granules, was investigated in the rat pituitary gland. Dexamethasone increased chromogranin A le...

Maiden, M.F.; Tanner, A.; McArdle, S.; Najpauer, K.; Goodson, J.M., 1991: Tetracycline fiber therapy monitored by DNA probe and cultural methods. Oligonucleotide DNA probe and selective cultural methods were compared in their ability to monitor 6 putative periodontal pathogens in a study evaluating local tetracycline fiber therapy. Subgingival plaque was sampled from 4 sites in each of 20 s...

Ohnishi S.T., 1989: Method of treating hemoglobinopathy us patent 4851404 july 25 1989. Official Gazette of the United States Patent & Trademark Office Patents 1104(4): 2687

Knipling, Edward B., 1967: Effect of leaf aging on water deficit-water potential relationships of dogwood leaves growing in two environments. Water deficit-water potential relationships were determined at approximately monthly intervals from May to Aug. on leaves collected from dogwood trees growing in 2 environments. The relationships were not the same for leaves of different ages or f...

Martin, J.E.; Jacobson, A.P.; Miklos, J.A., 1993: Michigan's public health program for indoor radon. American Journal of Public Health 83(10): 1488-1489

Fritsch Volker, 1950: Einige funkgeologische Untersuchungen nach der Ersatzkapazitaets- und Ausbreitungs-methode mit nahem Sender und die Moeglichkeit einer indirekten Anzeige tiefer elektrischer Diskontinuitaeten. Discusses some of the problems connected with radiogeological prospecting for deep-seated structures, especially zones of tectonic disturbance.

Sandbu, R.; Khamis, H.; Gustavsson, S.; Haglund, U., 2002: Long-term results of antireflux surgery indicate the need for a randomized clinical trial. Well conducted, comparative trials of laparoscopic versus open antireflux surgery with an adequate patient enrollment are few and they do not demonstrate obvious advantages for the laparoscopic approach except for a marginal gain in shorter hospit...

Wethey, D.S.; Zimmer Faust, R.K.; Pentcheff, N.D.; Finelli, C., 1993: How odor plumes are used in the field A crustacean predator and its prey. American Zoologist 33(5): 112A

Szymaniec, J.; Zielinski, M., 1977: Palliative analgesic treatment in neoplastic diseases. Wiadomosci Lekarskie 30(7): 535-538