An In Silico Analysis Reveals Sustained Upregulation of Neuroprotective Genes in the Post-Stroke Human Brain

Abstract

Ischemic stroke is a cerebrovascular disease caused by an interruption of blood flow to the brain, thus determining a lack of oxygen and nutrient supply. The ischemic event leads to the activation of several molecular signaling pathways involved in inflammation and the production of reactive oxygen species, causing irreversible neuronal damage. Several studies have focused on the acute phase of ischemic stroke. It is not clear if this traumatic event can influence some of the molecular processes in the affected area even years after the clinical event. In our study, we performed an in silico analysis using freely available raw data with the purpose of evaluating the transcriptomic state of post-mortem brain tissue. The samples were taken from non-fatal ischemic stroke patients, meaning that they suffered an ischemic stroke and lived for a period of about 2 years after the event. These samples were compared with healthy controls. The aim was to evaluate possible recovery processes useful to mitigating neuronal damage and the detrimental consequences of stroke. Our results highlighted differentially expressed genes codifying for proteins along with long non-coding genes with anti-inflammatory and anti-oxidant functions. This suggests that even after an amount of time from the ischemic insult, different neuroprotective mechanisms are activated to ameliorate brain conditions and repair post-stroke neuronal injury.

Keywords: human brain; in silico analysis; ischemic stroke; neuroinflammation; neuroprotection; oxidative stress; post-stroke; transcriptome.

Figure 1

PCA of samples retrieved in PRJNA242801 differentiated by the healthy (red) and stroke (blue) groups. PC1 strongly splits the SRR1206045, SRR1206046, and SRR1206047 samples from the remaining samples, highlighting a variance of 78%. Instead, the PC2 cluster split all of the samples quite well even if SRR1206040 is a bit of a distance away but with a small variance of just 7%.

Figure 2

PCA of the final cohort with samples differentiated into the healthy (red) and the stroke (blue) groups. PC1 has very little variance between the samples (only 42%), so the two groups are comparable.

Figure 3

The expression level of each of the 23 DEGs identified in the comparative analysis between the healthy and stroke groups for each sample in the blue palette. The expression level of the counts was scaled from 0 to 1 and then normalized in a log scale of the normalized expression level count. Transcripts not expressed in a sample are painted in gray. From left to right the blue palettes represent samples SRR1206035, SRR1206036, SRR1206037, SRR1206038, SRR1206039, SRR1206040, SRR1206041, SRR1206042, SRR1206043, and SRR1206044. The comparative analysis shows upregulated DEGs in the red palette and downregulated DEGs in the green palette.

Figure 4

Classification of the DEGs involved in stroke. In the figure, we highlighted how the DEGs found in stroke can be included in the main categories “Neuroprotection”, “Brain reorganization”, “Inflammation and stress”, and “Long non coding”. Red DEGs are more expressed after stroke while green DEGs are less expressed after stroke.