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Updated: Jan 5, 2026
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
Acute Downregulation of Novel Hypothalamic Protein Sushi Repeat-Containing Protein X-Linked 2 after Experimental
Mehwish Anwer1, Leonardo Lara-Valderrabano1, Jenni Karttunen1
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Abstract:
Traumatic brain injury (TBI) causes damage to the hypothalamo-hypophyseal axis, leading to endocrine dysregulation in up to 40% of TBI patients. Hence, there is an urgent need to identify non-invasive biomarkers for TBI-associated hypothalamo-hypophyseal pathology. Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel hypothalamic protein expressed in both rat and human brain. Our objective was to investigate the effect of acquired brain injury on plasma SRPX2 protein levels and SRPX2 expression in the brain. We induced severe lateral fluid-percussion injury in adult male rats and investigated changes in SRPX2 expression at 2 h, 6 h, 24 h, 48 h, 72 h, 5 days, 7 days, 14 days, 1 month, and 3 months post-injury. The plasma SRPX2 level was assessed by Western blot analysis. Hypothalamic SRPX2-immunoreactive neuronal numbers were estimated from immunostained preparations. At 2 h post-TBI, plasma SRPX2 levels were markedly decreased compared with the naïve group (area under the curve = 1.00, p < 0.05). Severe TBI caused a reduction in the number of hypothalamic SRPX2-immunoreactive neurons bilaterally at 2 h post-TBI compared with naïve group (5032 ± 527 vs. 9440 ± 351, p < 0.05). At 1 month after severe TBI, however, the brain and plasma SRPX2 levels were comparable between the TBI and naïve groups (p > 0.05). Unsupervised hierarchical clustering using SRPX2 expression differentiated animals into injured and uninjured clusters. Our findings indicate that TBI leads to an acute reduction in SRPX2 protein expression and reduced plasma SRPX2 level may serve as a candidate biomarker of hypothalamic injury.
Insights
Traumatic brain injury (TBI) acutely reduces plasma Sushi repeat-containing protein X-linked 2 (SRPX2) levels and hypothalamic expression. Reduced plasma SRPX2 may serve as a biomarker for TBI-induced hypothalamo-hypophyseal injury.
Area of Science:
- Neuroscience
- Endocrinology
- Biomarker Discovery
Background:
- Traumatic brain injury (TBI) frequently damages the hypothalamo-hypophyseal axis, causing endocrine dysregulation in up to 40% of patients.
- There is a critical need for non-invasive biomarkers to detect TBI-associated hypothalamo-hypophyseal pathology.
- Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel hypothalamic protein found in both rat and human brains.
Purpose of the Study:
- To investigate the impact of acquired brain injury on plasma SRPX2 protein levels.
- To examine changes in SRPX2 expression within the brain following TBI.
- To evaluate the potential of SRPX2 as a biomarker for TBI-induced hypothalamic injury.
Main Methods:
- Severe lateral fluid-percussion injury was induced in adult male rats.
- Plasma SRPX2 levels were measured using Western blot analysis at various time points post-injury.
- Hypothalamic SRPX2-immunoreactive neuronal counts were determined via immunostaining.
Main Results:
- Plasma SRPX2 levels were significantly decreased at 2 hours post-TBI compared to controls.
- A reduction in hypothalamic SRPX2-immunoreactive neurons was observed bilaterally at 2 hours post-TBI.
- By 1 month post-TBI, plasma and brain SRPX2 levels returned to levels comparable to the control group.
- Hierarchical clustering based on SRPX2 expression successfully differentiated injured from uninjured animals.
Conclusions:
- TBI causes an acute reduction in SRPX2 protein expression in both plasma and the hypothalamus.
- Decreased plasma SRPX2 levels show potential as an early, non-invasive biomarker for hypothalamic injury following TBI.
- SRPX2 expression patterns can distinguish between TBI-affected and unaffected individuals.
