<p>Intracerebral Hemorrhage Induced Brain Injury Is Mediated by the Interleukin-12 Receptor in Rats</p>

Abstract

Background: IL-12 inhibition of the endothelial cell functions and angiogenesis is mediated by the cross-talk between the lymphocyte and the endothelial cells, which plays a key role in inhibiting the process of angiogenesis in the eyeballs and in malignant tumors. Methods: We established the intracerebral hemorrhage (ICH) rat model, and IL-12 receptor beta monoclonal antibody was injected into the ICH rats. Western blot, immunofluorescence and RT-qPCR were used to detect the gene expression. Brain water content, EB staining, Garcia test, Beam walking test and wire hanging test were used to assess the injury of brain in ICH rats. Results: IL-12 gene was significantly increase in hematoma border tissue of ICH rats, and IL-12 protein mainly localized in monocytes. Anti-IL-12 treatment with IL-12 monoclonal antibodies could not only significantly decrease the brain water content and EB content in brain tissues of ICH rats, but also significantly increase the score of the Garcia, Beam balance and the Wire hanging test in ICH rats. Moreover, anti-IL-12 treatment significantly decrease the expression of pro-inflammatory gene, inflammatory gene, p-JAK2/JAK2 and p-STAT4/STAT4 protein, but significantly increase the expression anti-inflammatory gene and CD31 protein, and M2 macrophage ratio in hematoma border tissues of ICH rats. In vitro, rmIL-12 inhibited the tube formation of brain microvascular endothelial cells (BMVES) in BMVES and bone marrow-derived monocytes (BMDM) co-culture systems, but not work in a separately cultured BMVES system. In addition, Fedratinib not only reduced p-JAK2/JAK2 and p-STAT4/STAT4 protein expression in BMDM after treating with b-FGF and rmIL-12, but also significantly increased the tube formation of BMVES in BMVES and BMDM co-culture systems after treating with b-FGF and rmIL-12. Conclusion: Blockade of IL-12 receptor attenuated brain injury after ICH in rat by promoting angiogenesis, and the mechanism might be related to blocking IL-12 could inhibit M2 cell activation via the JAK2/STAT4 pathway.

Relationship of Serum IL-12 to Inflammation, Hematoma Volume, and Prognosis in Patients With Intracerebral Hemorrhage

“…As a disease closely related to inflammation, we speculate that IL-12 may be involved in the inflammatory cascade after intracerebral hemorrhage. Consistently, IL-12 was found to be highly expressed in the brain tissue of animal models of cerebral hemorrhage and blocking the activity of IL-12 by antibodies could reduce inflammation and attenuate brain damage caused by cerebral hemorrhage [ 16 ].…”

“…Previous studies have shown that the expression of IL-12 is elevated around the hematoma in animal models of cerebral hemorrhage, and the use of IL-12 receptor monoclonal antibody can alleviate brain injury after intracerebral hemorrhage. Its mechanism is thought to be involved in regulating macrophage activation [ 16 ]. However, no study has investigated serum IL-12 levels in patients with ICH, nor has there been a study investigating the relationship between serum IL-12 levels and circulating inflammation, hematoma volume, early neurological deterioration, and 3-month prognosis in patients with ICH.…”

miR‑30e‑5p attenuates neuronal deficit and inflammation of rats with intracerebral hemorrhage by regulating TLR4

“…The rats underwent BBT, in which they were allowed to walk on a balance beam (square stick; length, 80.0 cm; width, 2.5 cm; 10.0 cm above ground) to walk on. The following six-grade standard was applied ( 28 ): 0, jump on the balance beam and walk without falling; 1, jump on the balance beam with time of falling ≤50%; 2, jump on the balance beam with time of falling >50%; 3, jump on the balance beam with the healthy lateral hind limb with no movement of paralyzed hind limb; 4, sit on the balance beam without walking and 5, fall from the balance beam.…”

Effects and mechanisms of CTRP3 overexpression in secondary brain injury following intracerebral hemorrhage in rats

“…Lower scores are indicative of more serious neuronal damage. In the beam walking test ( 23 ), a square wood bar (590 x 25 mm) was placed 100 mm from the ground. Each rat was allowed to walk on the balance beam.…”