The neuroprotective effect of pretreatment with carbon dots from Crinis Carbonisatus (carbonized human hair) against cerebral ischemia reperfusion injury

Abstract

Background Cerebral infarction and cerebral hemorrhage, also known as “stroke”, is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years. Results In this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity. Conclusion CrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs. Graphic abstract

Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia/reperfusion injury

“…Other studies also reported that the hyperphosphorylation of tau increases during MCAO/R in animal models ( Dong et al, 2014 ; Fujii et al, 2017 ). Tnf was also reported to be significantly upregulated in MCAO/R animal models and OGD/R cell models ( Li et al, 2019 ; Zhang et al, 2021a ; Zhou et al, 2021 ). Moreover, it was reported that miR-181a-5p was highly expressed in serum of ischemic stroke patients, brain tissues of MCAO/R mice, and an oxygen-glucose-deprivation/reoxygenation (OGD/R) N2a cell model ( Ouyang et al, 2012 ; Wu et al, 2017 ; Song et al, 2021 ).…”

“…Many studies have demonstrated that the inhibition of TNF signaling pathways may have neuroprotective effects against cerebral I/R injury. For example, Zhang et al showed that preconditioning with Carbonisatus significantly decreased the levels of TNF-α and IL-6, reduced ischemic lesion volume, and improved neurological deficits in MCAO/R rats ( Zhang et al, 2021a ).…”

Protective Effects of Carbon Dots Derived from Armeniacae Semen Amarum Carbonisata Against Acute Lung Injury Induced by Lipopolysaccharides in Rats

“…Through preparatory work, our investigation group has demonstrated that CDs are the material basis for the activity of charcoal drugs. We have reported that the carbonisata-derived CDs of charcoal drugs such as Junci Medulla 31 have remarkable anti-haemorrhage effects and CDs derived from Crinis Carbonisatus 32 perform neuroprotective effect on cerebral ischemia and reperfusion injury. In addition, Aurantii fructus immaturus 14 carbonisata-derived carbon dots have anti-hyperuricaemic and anti-gouty arthritis activity, which can diminish serum uric acid by restraining xanthine oxidase activity in hyperuricaemic rats and in vitro.…”

Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy

“…More importantly, although collagen plays a key role in cell-ECM adhesion, another two components of ECM (namely, fibronectin and integrin) are needed as well, since the establishment of the cell-ECM connections is via the binding of fibronectin to collagen and cell-surface integrin [ 11 ]. With excellent biocompatibility, strong fluorescence properties, and nanoscale size, carbon dots (CDots) as an emerging class of carbon-based nanomaterials have great potential in various biomedical applications, including anti-inflammation [ 32 ], bacteriostasis [ 33 ], bioimaging [ 34 ] and so on [ 35 , 36 ]. A majority of CDots are usually prepared from the organic precursors with carbonyl and amine groups through amidation reaction similar to the formation of peptide bond in protein.…”