Puerarin was shown to exert anti-oxidative and anti-ferroptosis effects in multiple diseases. The goal of this study was to explore the neuroprotective effect of puerarin on early brain injury (EBI) after subarachnoid hemorrhage (SAH) in rats. A total of 177 adult male Sprague Dawley rats were used. SAH was included via endovascular perforation. Intranasal puerarin or intracerebroventricular dorsomorphin (AMPK inhibitor) and SR18292 (PGC1α inhibitor) were administered. The protein levels of pAMPK, PGC1α, Nrf2, 4HNE, HO1, MDA, ACSL4, GSSG, and iron concentration in the ipsilateral hemisphere were significantly increased, whereas SOD, GPX4, and GSH were decreased at 24 h after SAH. Moreover, puerarin treatment significantly increased the protein levels of pAMPK, PGC1α, Nrf2, HO1, SOD, GPX4, and GSH, but decreased the levels of 4HNE, MDA, ACSL4, GSSG, and iron concentration in the ipsilateral hemisphere at 24 h after SAH. Dorsomorphin or SR18292 partially abolished the beneficial effects of puerarin exerted on neurological dysfunction, oxidative stress injury, and ferroptosis. In conclusion, puerarin improved neurobehavioral impairments and attenuated oxidative-stress-induced brain ferroptosis after SAH in rats. The neuroprotection acted through the activation of the AMPK/PGC1α/Nrf2-signaling pathway. Thus, puerarin may serve as new therapeutics against EBI in SAH patients.

The goal of our study was to explore the significant association between a non-protein coding single nucleotide polymorphism (SNP) rs4977574 of CDKN2BAS gene and coronary heart disease (CHD). A total of 590 CHD cases and 482 non-CHD controls were involved in the present association study. A strong association of rs4977574 with CHD was observed in females (genotype: p = 0.002; allele: p = 0.002, odd ratio (OR) = 1.57, 95% confidential interval (CI) = 1.18–2.08). Moreover, rs4977574 was more likely to be a risk variant of CHD under the recessive model in females (χ² = 10.29, p = 0.003, OR = 2.14, 95% CI = 1.31–2.77). A breakdown analysis by age had shown that there was an 87% increased risk of CHD for females younger than 65 years (genotype: χ² = 14.64, degrees of freedom (df) = 2, p = 0.0002; allele: χ² = 11.31, df = 1, p = 0.0008, OR = 1.87, 95% CI = 1.30–2.70). Similar observation was also found in males younger than 65 years (genotype: χ² = 8.63, df = 2, p = 0.04; allele: χ² = 7.55, df = 1, p = 0.006, OR = 1.45, 95% CI = 1.11–1.90). p values were adjusted by age, sex, smoking, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Meta-analysis of 23 studies among 36,452 cases and 39,781 controls showed a strong association between rs4977574 and the risk of CHD (p < 0.0001, OR = 1.27, 95% CI = 1.22–1.31).

Peripheral nerve injuries have become a common clinical disease with poor prognosis and complicated treatments. The development of tissue engineering pointed a promising direction to produce nerve conduits for nerve regeneration. Electrical and mechanical stimulations have been incorporated with tissue engineering, since such external stimulations could promote nerve cell proliferation, migration and differentiation. However, the combination of electrical and mechanical stimulations (electromechanical stimulation) and its effects on neuron proliferation and axon outgrowth have been rarely investigated. Herein, silver nanowires (AgNWs) embedded polydimethylsiloxane (PDMS) electrodes were developed to study the effects of electromechanical stimulation on rat pheochromocytoma cells (PC12 cells) behaviors. AgNWs/PDMS electrodes demonstrated good biocompatibility and established a stable electric field during mechanical stretching. PC12 cells showed enhanced proliferation rate and axon outgrowth under electrical stimulation alone, and the cell number significantly increased with higher electrical stimulation intensity. The involvement of mechanical stretching in electrical stimulation reduced the cell proliferation rate and axon outgrowth, compared with the case of electrical stimulation alone. Interestingly, the cellular axons outgrowth was found to depend on the stretching direction, where the axons prefer to align perpendicularly to the stretch direction. These results suggested that AgNWs/PDMS electrodes provide an in vitro platform to investigate the effects of electromechanical stimulation on nerve cell behaviors and can be potentially used for nerve regeneration in the future.

Caspases are an evolutionarily conserved family of proteases responsible for mediating and initiating cell death signals. In the past, the dysregulated activation of caspases was reported to play diverse but equally essential roles in neurodegenerative diseases, such as brain injury and neuroinflammatory diseases. A subarachnoid hemorrhage (SAH) is a traumatic event that is either immediately lethal or induces a high risk of stroke and neurological deficits. Currently, the prognosis of SAH after treatment is not ideal. Early brain injury (EBI) is considered one of the main factors contributing to the poor prognosis of SAH. The mechanisms of EBI are complex and associated with oxidative stress, neuroinflammation, blood‐brain barrier disruption, and cell death. Based on mounting evidence, caspases are involved in neuronal apoptosis or death, endothelial cell apoptosis, and increased inflammatory cytokine‐induced by apoptosis, pyroptosis, and necroptosis in the initial stages after SAH. Caspases can simultaneously mediate multiple death modes and regulate each other. Caspase inhibitors (including XIAP, VX‐765, and Z‐VAD‐FMK) play an essential role in ameliorating EBI after SAH. In this review, we explore the related pathways mediated by caspases and their reciprocal regulation patterns after SAH. Furthermore, we focus on the extensive crosstalk of caspases as a potential area of research on therapeutic strategies for treating EBI after SAH.

The superior sagittal sinus (SSS) and transverse sinus are the major dural sinuses that receive a considerable amount of venous drainage. The occlusion of them has been suggested to cause intracranial hypertension, hemorrhage, and lead to potentially fatal consequences. We reported a 35-year-old woman with headache presented to our emergency department with a decreased level of consciousness and epileptic seizures. The examination of speech, higher mental function, and cranial nerve were normal. Computed tomography (CT) demonstrated both subarachnoid and intraparenchymal hemorrhage and brain edema at the right temporal lobe accompanied by high density shadow in the right transverse sinus. Digital subtraction angiography (DSA) revealed extensive thrombosis of the SSS and bilateral transverse sinus. The SSS and transverse sinus thrombosis, accompanied by right temporal lobe hemorrhage, subarachnoid hemorrhage (SAH). An emergent mechanical thrombectomy by placed Solitair AB stent in the SSS, respectively, passed left and right sigmoid sinus–transverse sinus route. We removed the most clots, DSA revealed recanalization of the SSS and left transverse sinus was seen with normalization of the venous outflow, the occlusion of right transverse sinus was still present. There were 4 hours after patient back to neurosurgical intensive care unit (NICU), patient appeared anisocoria (R/L:4.0/2.5 mm), bilateral light reflexes disappeared, then we took a CT reexamination revealed intraparenchymal hemorrhage increased, brain edema was aggravated at the left temporal lobe, and mild midline shift. Subsequently, we performed decompressive hemicraniectomy and puncture the hematoma supplemented by B ultrasonic. Anticoagulation treatment was initiated 24 hours after surgery, and follow-up DSA showed gradually improved patency in the SSS and bilateral transverse sinus. Despite occlusion of the SSS and bilateral transverse sinus, patient's symptoms resolved after the operations and he was discharged without complications. The favorable clinical outcome after complete occlusion of the SSS and transverse sinus, accompanied by right temporal lobe hemorrhage, SAH has rarely been reported and it might be explained by our timely surgical intervention and development of compensatory cerebral collateral circulation.