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Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study.

Lackner P, Part A, Burger C, Dietmann A, Broessner G, Helbok R, Reindl M, Schmutzhard E, Beer R - Malar. J. (2009)

Bottom Line: The drug had no effect on the course of parasitaemia.The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals.No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at

ABSTRACT

Background: Cerebral malaria (CM) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. Studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine CM indicate promising potential. The current study was conducted to evaluate the efficacy of glatiramer acetate (GA), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of C57Bl/6J mice infected with Plasmodium berghei ANKA.

Methods and results: GA treatment led to a statistically significant lower risk for developing CM (57.7% versus 84.6%) in treated animals. The drug had no effect on the course of parasitaemia. The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals. No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.

Conclusion: These findings support the important role of the host immune response in the pathophysiology of murine CM and might lead to the development of new adjunctive treatment strategies.

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Related in: MedlinePlus

Histological analysis of microhaemorrhages, activated caspase-3 positive cells and brain sequestered leukocytes. Stereological analysis of histology of GA (open bars) and vehicle (filled bars) treated animals. A: Relative of microhaemorrhages affected brain area in moribund CM animals. B: Total number of parenchymal cells immunopositive for activated caspase-3 on day 4 post-infection and in moribund CM animals. C: Total number of brain sequestered leukocytes on day 4 post-infection and in moribund CM animals. Mean values and SEM are shown.
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Figure 3: Histological analysis of microhaemorrhages, activated caspase-3 positive cells and brain sequestered leukocytes. Stereological analysis of histology of GA (open bars) and vehicle (filled bars) treated animals. A: Relative of microhaemorrhages affected brain area in moribund CM animals. B: Total number of parenchymal cells immunopositive for activated caspase-3 on day 4 post-infection and in moribund CM animals. C: Total number of brain sequestered leukocytes on day 4 post-infection and in moribund CM animals. Mean values and SEM are shown.

Mentions: Histopathological changes were quantified by stereological methods. In moribund CM animals the relative haemorrhagic brain area was not significantly different between GA and vehicle treated animals (Figure 3A). The relative number of activated caspase-3 immunopositive brain parenchymal cells on day 4 post-infection and in moribund CM animals was not significantly different between GA and vehicle-treated animals (Figure 3B). On day 11 post-infection no activated caspase-3 immunopositive cells could be observed. Densitometric analysis of Western blots did not show significant difference for activated caspase-3 between GA and vehicle treated mice on day 4 post-infection or in moribund animals.


Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study.

Lackner P, Part A, Burger C, Dietmann A, Broessner G, Helbok R, Reindl M, Schmutzhard E, Beer R - Malar. J. (2009)

Histological analysis of microhaemorrhages, activated caspase-3 positive cells and brain sequestered leukocytes. Stereological analysis of histology of GA (open bars) and vehicle (filled bars) treated animals. A: Relative of microhaemorrhages affected brain area in moribund CM animals. B: Total number of parenchymal cells immunopositive for activated caspase-3 on day 4 post-infection and in moribund CM animals. C: Total number of brain sequestered leukocytes on day 4 post-infection and in moribund CM animals. Mean values and SEM are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651188&req=5

Figure 3: Histological analysis of microhaemorrhages, activated caspase-3 positive cells and brain sequestered leukocytes. Stereological analysis of histology of GA (open bars) and vehicle (filled bars) treated animals. A: Relative of microhaemorrhages affected brain area in moribund CM animals. B: Total number of parenchymal cells immunopositive for activated caspase-3 on day 4 post-infection and in moribund CM animals. C: Total number of brain sequestered leukocytes on day 4 post-infection and in moribund CM animals. Mean values and SEM are shown.
Mentions: Histopathological changes were quantified by stereological methods. In moribund CM animals the relative haemorrhagic brain area was not significantly different between GA and vehicle treated animals (Figure 3A). The relative number of activated caspase-3 immunopositive brain parenchymal cells on day 4 post-infection and in moribund CM animals was not significantly different between GA and vehicle-treated animals (Figure 3B). On day 11 post-infection no activated caspase-3 immunopositive cells could be observed. Densitometric analysis of Western blots did not show significant difference for activated caspase-3 between GA and vehicle treated mice on day 4 post-infection or in moribund animals.

Bottom Line: The drug had no effect on the course of parasitaemia.The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals.No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. peter.lackner@i-med.ac.at

ABSTRACT

Background: Cerebral malaria (CM) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. Studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine CM indicate promising potential. The current study was conducted to evaluate the efficacy of glatiramer acetate (GA), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of C57Bl/6J mice infected with Plasmodium berghei ANKA.

Methods and results: GA treatment led to a statistically significant lower risk for developing CM (57.7% versus 84.6%) in treated animals. The drug had no effect on the course of parasitaemia. The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals. No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.

Conclusion: These findings support the important role of the host immune response in the pathophysiology of murine CM and might lead to the development of new adjunctive treatment strategies.

Show MeSH
Related in: MedlinePlus