Effect of Liraglutide on brain water content and Neuroscore after TBI.

<p>A: Ipsilateral total water content of the 6 mm coronal sample area (Ipsi-Total) and corresponding contralateral region (Ctrl-Total) 48 hours following controlled cortical impact (CCI). Total water content increased significantly in vehicle treated animals compared to Sham. However, water content was mitigated significantly in animals treated with Liraglutide 200 μg/kg BID. B: Subregion water content of contralateral and ipsilateral areas 48 hours after CCI. Liraglutide 200 μg/kg BID significantly mitigated cerebral water content in the ipsilateral hippocampus and thalamus after CCI. C: Composite Neuroscore test was calculated through a battery of six sub-tests 48 hours after CCI, with a score of maximum 21 points. Values in A and B are means ± SEM. *:p<0.05, **:p<0.01. Values in C are presented as median and error bars indicate the 25^th and 75^th percentile. Abbreviations: LIR75—Liraglutide 75 μg/kg; n = 10, LIR200—Liraglutide 200 μg/kg; n = 10, vehicle n = 10 and Sham n = 4.</p

Experimental outline.

<p>Flow diagram of the three experiments. The colored dots indicate treatment with a subcutaneous dose of Liraglutide 75 μg/kg (LIR75), Liraglutide 200 μg/kg (LIR200) or vehicle. Abbreviations: Controlled cortical impact (CCI), days (d), experiment (exp), Paw-placement test (PP-test).</p

Effect of Liraglutide on normal brain water content and Neuroscore.

<p>Water content in the uninjured naive brain was unaffected by Liraglutide 200 μg/kg 48 hours after CCI. Values are means ± SEM. B: There was no effect of Liraglutide on Neuroscore in naive animals. Values are median with 25^th and 75^th percentile.</p

Effects on lesion volume and delayed neuronal death 7 days post-injury.

<p>A: Illustration of representative lesions by NeuN stained coronal sections from rats treated either with vehicle or Liraglutide for two days. The successive coronal sections range from +2.2 to -6.8 mm from bregma. B: Calculated cortical lesion volume (mm³). C: Calculated lesion volume in the ipsilateral thalamus (mm³). D: NeuN stained coronal section -2.8 mm from bregma illustrating the 5 regions of interest (ROI) chosen for investigation of FJC+ cells within the thalamus. Each ROI represents a counting frame at 10X. E: Demonstration of counting frame with FJC+ cells 7 days after CCI. F: Degenerating neurons shown at 20X. G: The average number of FJC+ cells for the 5 ROI’s was unaffected by Liraglutide treatment for the first 2 days post injury. *:p<0.05. Values are means ± SEM.</p

Paw placement and Circling test (experiment 2 and 3).

<p>Performance of vehicle- and Liraglutide-treated rats in Circling test 2 days (A) and 7 days (B) after controlled cortical impact (CCI), and limb-placing ability for 2 days (C) and 7 days (D) after CCI. The normal score before injury is 2 for circling test and 4 for paw placement test. Values are presented as median and error bars indicate the 25^th and 75^th percentile, #:p<0.05.</p

Evans blue exudation.

<p>A: Analysis of Evans Blue extravasation (μg/mg of dry brain tissue) 48 hours after CCI in rats. Treatment with Liraglutide 200 μg/kg BID significantly reduced Evans Blue extravasation in both hemispheres. B: Illustration of coronal sections through the contusion center illustrates Evans blue distribution throughout the rat brain. Evans blue extravasation is particularly prominent in the pericontusional cortex, hippocampus and upper thalamus. Values are mean ± SEM. *:p<0.05.</p

MOESM6 of Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation

Additional file 6: Table S6. Regulated genes involved in development in all experimental groups classified by gene ontology. Abbreviations: D—dobutamine; LPS—lipopolysaccharide; OGD—oxygen–glucose-deprivation

MOESM3 of Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation

Additional file 3: Table S3. Regulated genes involved in mechanisms of cell death and cell survival in all experimental groups classified by gene ontology. Abbreviations: D—dobutamine; LPS—lipopolysaccharide; OGD—oxygen–glucose-deprivation

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Additional file 7: Table S7. Regulated genes involved in cytoskeleton and extracellular matrix dynamics in all experimental groups classified by gene ontology. Abbreviations: D—dobutamine; LPS—lipopolysaccharide; OGD—oxygen–glucose-deprivation

MOESM5 of Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation

Additional file 5: Table S5. Regulated genes involved in growth and cell cycle related mechanisms in all experimental groups classified by gene ontology. Abbreviations: D—dobutamine; LPS—lipopolysaccharide; OGD—oxygen–glucose-deprivation