Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.

Clinical significance of low T3 syndrome in different subtypes of cerebral infarction / 中华神经医学杂志

Objective To explore the mechanism underlying the poor prognosis in cerebral infarction (CI) patients with low T3 syndrome by comparing the NIHSS scores in these patients with or without low T3 syndrome.Methods One hundred and sixty-two patients with CI,admitted to our hospital from January 2010 to December 2012,were chosen in our study; the levels of thyroid hormones,including triiodothyronine (T3),four iodine thyronine (T4),thyroid stimulating hormone (TSH),free Triiodothyronine (iT3) and free four iodine thyronine (fT4),were measured by radioimmunoassay.CI lesions and TOAST distribution were determined by cranial MRI,magnetic resonance angiography (MRA) or CT angiography (CTA),and carotid ultrasonography.NIHSS scores at the worst in cerebral infarction inpatients were detected.Results In the 162 patients with CI,29 patients (17.90％) were combined with low T3 symptom and 20 had fT3 level lower than the lowest normal level (2.63 pmol/L); and T4,fT4 and TSH levels were within normal limits.T3,fr3 and TSH levels in patients with low T3 symptom were significantly lower than those of patients without low T3 symptom (P＜0.05).The distribution of TOAST showed no significant difference between patients with low T3 symptom and patients without low T3 symptom (P＞0.05).In patients with large artery atherosclerosis-internal carotid artery,the NIHSS scores at the worst in patients with low T3 level were significantly higher as compared with those in patients with normal T3 levels (P＜0.05).Conclusion The neurologic impairment is more severe in large artery atherosclerosis-intemal carotid artery patients with low T3 level than those without low T3 level,which might be responsible for the poor prognosis of the illness with low T3 syndrome.