T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors/Interferon Regulatory Factor/P53 Upregulated Modulator of Apoptosis/Dynamin‐1‐Like Protein Pathway

Abstract

Background and Purpose. T0901317, a liver X receptor (LXR) agonist, is widely used to explore the functions of LXRs. T0901317 exerts antiapoptotic effects in many central nervous system disease models. Our aim was to detect the role of T0901317 in neuronal apoptosis in early brain injury after subarachnoid hemorrhage. Methods. Subarachnoid hemorrhage (SAH) models of Sprague-Dawley rats were established with perforation method. T0901317 was injected intraperitoneally 1-hour post-SAH. GSK2033, an inhibitor of LXRs, and interferon regulatory factor (IRF-1) CRISPR activation were injected intracerebroventricularly to evaluate potential signaling pathway. The severity of SAH, neurobehavior test in both short- and long-term and apoptosis was measured with Western blot and immunofluorescence staining. Results. Expression of LXR-α and IRF-1 increased and peaked at 24 h post-SAH, while LXR-β remained unaffected in SAH+vehicle group compared with Sham group. Post-SAH T0901317 treatment attenuated neuronal impairments in both short- and long-term and decreased neuronal apoptosis, the expression of IRF-1, P53 upregulated modulator of apoptosis (PUMA), dynamin-1-like protein (Drp1), Bcl-2-associated X protein (Bax) and cleaved caspase-3, and increasing B-cell lymphoma 2 (Bcl-2) at 24 h from modeling. GSK2033 inhibited LXRs and reversed T0901317’s neuroprotective effects. IRF-1 CRISPR activation upregulated the expression of IRF-1 and abolished the treatment effects of T0901317. Conclusion. T0901317 attenuated neuronal apoptosis via LXRs/IRF-1/PUMA/Drp1 pathway in SAH rats.

Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway

“…In the present study, activation of the RARα promoted M1-to-M2 phenotypic polarization of microglia in an in vitro model of SAH. Apoptosis, as an important regulatory mechanism of cell death, is involved in the pathological processes underlying many diseases ( 46 , 47 ). Activation of the RARα with Am80 significantly suppressed neuronal apoptosis after SAH; this was consistent with previous research ( 14 ) and suggests that the activation of RARα attenuates the neurotoxic effects of activated microglia by suppressing the production of inflammatory cytokines.…”

Cycloastragenol Confers Cerebral Protection after Subarachnoid Hemorrhage by Suppressing Oxidative Insults and Neuroinflammation via the SIRT1 Signaling Pathway

“…Accumulating evidence has revealed that oxidative damage and inflammatory response play critical roles in the pathogenesis of SAH [ 25 – 29 ]. Diminishing oxidative damage and inflammatory response could significantly improve neurological outcome after SAH [ 30 – 33 ].…”

ASK1 inhibitor NQDI‑1 decreases oxidative stress and neuroapoptosis via the ASK1/p38 and JNK signaling pathway in early brain injury after subarachnoid hemorrhage in rats

“…Modified Garcia score and the beam balance score were used to assess the short-term neurological function 24 h after SAH. The modified Garcia score was divided into six categories as follows: Voluntary movement, voluntary limb movement, forepaw extension, climbing ability, somatosensory responses and tentacle response, each of which was scored individually and summed to give a total score ranging from 3–18 ( 25 ). Higher scores were considered to indicate better neurological function.…”