Sleep contributes to the maintenance of overall health and well-being. There are a growing number of patients who have headache disorders that are significantly affected by poor sleep. This is a paradoxical relationship, whereby sleep deprivation or excess sleep leads to a worsening of headaches, yet sleep onset also alleviates ongoing headache pain. Currently, the mechanism of action remains controversial and poorly understood. The glymphatic system is a newly discovered perivascular network that encompasses the whole brain and is responsible for removing toxic proteins and waste metabolites from the brain as well as replenishing nutrition and energy. Recent studies have suggested that glymphatic dysfunction is a common underlying etiology of sleep disorders and headache pain. This study reviews the current literature on the relationship between the glymphatic system, sleep, and headaches, discusses their roles, and proposes acupuncture as a non-invasive way to focus on the glymphatic function to improve sleep quality and alleviate headache pain.

Ischemic stroke (IS) has been associated with an impairment in glymphatic function. Xuefu Zhuyu Decoction (XFZYD) is widely used in the prevention and treatment of ischemic stroke. We hypothesized that Xuefu Zhuyu decoction pretreatment could attenuate early neurological deficits after ischemic stroke by enhancing the function of the glymphatic system. To prove our hypothesis, we carried out temporary middle cerebral artery occlusion and reperfusion surgery on C57BL/6 mice and then measured neurological score, infarct size and performed hematoxylin-eosin staining to assess stroke outcomes after 24 h of reperfusion. Subsequently, we injected fluorescent tracers in to the cisterna magna and evaluated tracer distribution in coronal brain sections. The polarization of aquaporin-4 (AQP4), colocalization of aquaporin-4, α-dystroglycan, β-dystroglycan and agrin were determined by immunofluorescence. Our research showed that pretreatment with Xuefu Zhuyu decoction significantly alleviated neurological scores, neurological deficits and pathological abnormalities in a mouse model of ischemic stroke. Importantly, Xuefu Zhuyu decoction pretreatment enhanced cerebrospinal fluid influx, protected aquaporin-4 depolarization and promoted the colocalization of aquaporin-4 with its anchoring proteins in the brain. Our findings highlight novel mechanisms underlying the neuroprotective effect of Xuefu Zhuyu decoction pretreatment on ischemic stroke-induced brain damage through the glymphatic system. Xuefu Zhuyu decoction pretreatment may offer a promising approach to slow the onset and progression of ischemic stroke.

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines’ prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.

Background: This research sought to systematically evaluate the clinical effects of traditional Chinese medicine (TCM) intervention in the treatment of diabetic nephropathy (DN) and analyze changes in thyroid function in patients with DN. Methods: The PubMed, Embase, Medline, Ovid, Springer, and self-built databases were searched to screen literature on TCM intervention and the treatment of DN published from the establishment of the databases to January 1, 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was then employed to assess the risk of bias in literature, and Review Manager 5.3 was utilized for the meta-analysis. Results: A total of 20 randomized controlled trials (RCTs) were included in the study, involving 3,566 subjects, and meta-analysis results showed that the clinical treatment efficiency of the experimental group was dramatically higher than the control group [MD =6.22, 95% confidence interval (CI): 3.77–10.25, Z=7.17, P<0.00001]. Moreover, the serum creatinine (Scr), blood urea nitrogen (BUN), urine protein excretion rate (UAER), 24 h postoperative urine protein quantification, and tumor necrosis factor-alpha (TNF-α) of patients after TCM intervention were all remarkably inferior to those of the control group as seen in the following results: Scr, MD =−8.69, 95% CI: −9.92 to −7.47, Z=13.94, P<0.00001; BUN, MD =−1.74, 95% CI: − 2.48 to −1.00, Z=4.6, P<0.00001; UAER, MD =−26.16, 95% CI: −46.89 to −5.44, Z=2.47, P=0.01; 24 h postoperative urine protein quantification, MD =−0.54, 95% CI: −0.68 to −0.4, Z=7.4, P<0.00001; TNF-α, MD =−5.3, 95% CI: −9.15 to −1.46, Z=2.7, P=0.007; and high sensitivity C-reactive protein (hs-CRP), MD =−1.34, 95% CI: −1.9 to −0.78, Z=4.66, P<0.00001. Discussion: TCM intervention in DN is effective in treating the clinical symptoms of patients with this disease and has ideal therapeutic effects.