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. 2022 Dec 1;12(1):20788.
doi: 10.1038/s41598-022-24481-2.

Increase in repulsive guidance molecule-a (RGMa) in lacunar and cortical stroke patients is related to the severity of the insult

Aijaz Parray  1 , Naveed Akhtar  1 , Ghulam Jeelani Pir  1 , Sajitha V Pananchikkal  1 , Raheem Ayadathil  1 , Fayaz Ahmad Mir  2 , Reny Francis  1 , Ahmed Own  1 , Ashfaq Shuaib  3
Affiliations

Increase in repulsive guidance molecule-a (RGMa) in lacunar and cortical stroke patients is related to the severity of the insult

Aijaz Parray et al. Sci Rep. .

Abstract

Repulsive guidance molecule-a (RGMa) inhibits angiogenesis and increases inflammation. Animal models of cerebral ischemia have shown that an increased expression of RGMa leads to larger infarction and its inhibition attenuates effects of ischemia. We report on the relationship of RGMa to stroke types and severity. This is a prospective study in patients admitted to the stroke service in Qatar. We collected the clinical determinants, including NIHSS at admission, imaging and outcome at discharge and 90-days. RGMa levels were determined by measuring mRNA levels extracted from peripheral blood mononuclear cells (PBMCs) within 24 h of onset and at 5 days. There were 90 patients (lacunar: 64, cortical: 26) and 35 age-matched controls. RGMa mRNA levels were significantly higher in the stroke patients: day 1: 1.007 ± 0.13 versus 2.152 ± 0.19 [p < 0.001] and day-5: 3.939 ± 0.36 [p < 0.0001]) and significantly higher in patients with severe stroke (NIHSS ≥ 8) compared to milder symptoms (NIHSS < 8) at day 1 (NIHSS ≥ 8: 2.563 ± 0.36; NIHSS < 8: 1.947 ± 0.2) and day 5 (NIHSS ≥ 8: 5.25 ± 0.62; NIHSS < 8: 3.259 ± 0.419). Cortical stroke patients had marginally higher RGMa mRNA levels compared to lacunar stroke at day 1 (cortical stroke: 2.621 ± 0.46 vs lacunar stroke: 1.961 ± 0.19) and day 5 (cortical stroke: 4.295 ± 0.76 vs lacunar stroke: 3.774 ± 0.39). In conclusion, there is an increase in the level of RGMa mRNA in patients with acute stroke and seen in patients with lacunar and cortical stroke. The increase in RGMa mRNA levels is related to the severity of the stroke and increases over the initial 5 days. Further studies are required to determine the effects of the increase in RGMa on stroke recovery.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
RGMA mRNA levels in control vs stroke patients on stroke onset (day1) and 5 days post stroke (day5). Data was normalized and represented as fold units (mean ± SEM). One-way ANOVA with Tukey’s test was used for multiple comparison (p < 0.05 was considered statistically significant).
Figure 2
Figure 2
Relative RGMA mRNA levels in stroke sub-types (lacunar vs cortical) on stroke onset (day1) and 5 days post stroke (day5) in comparison to control. Data was normalized and represented as fold units (mean ± SEM). One-way ANOVA with Tukey’s test was used for multiple comparison (p < 0.05 was considered statistically significant).
Figure 3
Figure 3
Relative RGMA mRNA levels in stroke sub-types, mild (NIHSS < 8) vs more severe stroke (NIHSS ≥ 8) on stroke onset (day1) and 5 days post stroke (day5). Data was normalized and represented as fold units (mean ± SEM). t-test was used for comparison between the stroke sub-groups (p < 0.05 was considered statistically significant).
Figure 4
Figure 4
Relative RGMA mRNA levels in stroke SVD vs stroke no SVD on stroke onset (day1) and 5 days post stroke (day5). Data was normalized and represented as fold units (mean ± SEM). One-way ANOVA with Tukey’s test was used for multiple comparison (p < 0.05 was considered statistically significant; ns, not significant).
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