Early antiinflammatory therapy attenuates brain damage after sah in rats

Han

Biotechnology & Biotechnological Equipment

et al. 2020

The study aimed to identify key genes involved in cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). GSE46696 of basilar arteries of SAH mice and normal controls were downloaded from the Gene Expression Omnibus (GEO). Integrated microarray analysis was performed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analyses of DEGs were performed with ClueGO. The protein-protein interaction (PPI) networks were constructed using Cytoscape software. A total of 4103 DEGs were identified; among them, 254 DEGs (63 up-regulated genes and 191 down-regulated genes) showed significant differences at p < 0.05. GO analysis showed that the identified DEGs were over-represented in 16 GO terms. KEGG pathway analysis showed that pathways in immune inflammation were significantly enriched pathways for DEGs. DEGs with relatively frequent interactions after CVS secondary to SAH included MIKI,

Section: Resultsmentioning

confidence: 99%

Gene expression profiles and related immune-inflammatory factors in the cerebral arteries in mouse models of subarachnoid haemorrhage

Han

Biotechnology & Biotechnological Equipment

et al. 2020

“…Considering an inflammatory response due to aSAH, a neuroprotective effect of early treatment with anti-inflammatory drugs as corticosteroids showed a diminished brain damage and a reduced mortality in a rat model [ 56 ]. Even a non-significant trend to improved neurological recovery could be demonstrated.…”

Section: Role Of Neuroinflammation In Asahmentioning

confidence: 99%

Neuroprotective Strategies in Aneurysmal Subarachnoid Hemorrhage (aSAH)

Weiland

Beez

Westermaier

et al. 2021

IJMS

Self Cite

Aneurysmal subarachnoid hemorrhage (aSAH) remains a disease with high mortality and morbidity. Since treating vasospasm has not inevitably led to an improvement in outcome, the actual emphasis is on finding neuroprotective therapies in the early phase following aSAH to prevent secondary brain injury in the later phase of disease. Within the early phase, neuroinflammation, thromboinflammation, disturbances in brain metabolism and early neuroprotective therapies directed against delayed cerebral ischemia (DCI) came into focus. Herein, the role of neuroinflammation, thromboinflammation and metabolism in aSAH is depicted. Potential neuroprotective strategies regarding neuroinflammation target microglia activation, metalloproteases, autophagy and the pathway via Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1), NF-κB and finally the release of cytokines like TNFα or IL-1. Following the link to thromboinflammation, potential neuroprotective therapies try to target microthrombus formation, platelets and platelet receptors as well as clot clearance and immune cell infiltration. Potential neuroprotective strategies regarding metabolism try to re-balance the mismatch of energy need and supply following aSAH, for example, in restoring fuel to the TCA cycle or bypassing distinct energy pathways. Overall, this review addresses current neuroprotective strategies in aSAH, hopefully leading to future translational therapy options to prevent secondary brain injury.

Iron-chelating agent alleviates chronic hydrocephalus in an experimental model of subarachnoid hemorrhage

Havryliv,

Smolanka,

Smolanka

et al. 2024

INJ

Background. The iron-chelating agent is being tested in this research to see whether or not it may aid rats with experimental communicating hydrocephalus caused by an intraventricular blood clot. Subarachnoid hemorrhage (SAH) causes chronic post-hemorrhagic hydrocephalus (CPHH) in one-third of patients, and up to 45 % of patients require permanent cerebrospinal fluid diversion during follow-up, with about 50 % shunt failures within a year. Hemoglobin degradation products induce subarachnoid fibrosis and consequent hydrocephalus, with iron as a critical factor. Iron-chelating agents reduce iron overload after SAH. Materials and methods. Our study used Wistar rats weighing 250–500 g. The first group (the controls) was without surgery. In the sham group, 0.15 ml of normal saline was administered into the cisterna magna, followed by a second injection 48 hours later. A 0.15 ml blood injection into cisterna magna was followed by a 0.15 ml blood injection 48 hours later, which was performed in the third treatment group, a blood group minus minocycline (BGMM). The fourth double hemorrhagic group (blood group plus minocycline — BGPM) received iron-chelating agent — minocycline. Transcranial ultrasonography was used in all groups, assessing the Levene index (LI) in the rats before and after surgery. CPHH was defined as a ventricular index above the 97th percentile of the pre-intervention LI (1.297). Morphological signs of SAH (blood in subarachnoid space and ventricular wall damage) were evaluated histologically. Results. Ninety-seven operations were done in 50 rats with a 15% posthemorrhagic postoperative mortality. Hydrocephalus in the BGMM group occurred in 56 % of rats, according to the ultrasonography, and all had SAH features with ependymal integrity disruption, according to histological investigations. The introduction of minocycline in the BGPM group prevented an increase in LI after autologous blood injection (similar values of preoperative mean LI = 1.079 ± 0.096 and postoperative mean LI = 1.034 ± 0.058). The difference between BGMM and BGPM groups was highly significant, with a mean of 0.179 ± 0.029, t(41) = 6.12, p < 0.00001. Conclusions. Based on the findings, minocycline alleviates ventriculomegaly in rats. The data suggests that iron-chelating agents may be utilized to treat and prevent CPHH. By illustrating vascular disorders, the technology may become more valuable.