Protective effect of miconazole on rat myelin sheaths following premature infant cerebral white matter injury

Abstract

The aim of the present study was to investigate the protective effects of miconazole on myelin sheaths following cerebral white matter damage (WMD) in premature infant rats. Sprague Dawley rats (3-days-old) were randomly divided into four groups (n=30 each) as follows: Sham surgery group, WMD model group, 10 mg/kg/day treatment group and 40 mg/kg/day treatment group. A cerebral white matter lesion model was created by ligating the right common carotid artery for 80 min. Treatment groups were administered with 10 or 40 mg/kg miconazole at 4–8 days following birth (early treatment group) or 5–11 days following birth (late treatment group). Rats in the model group received the same concentration of dimethylsulfoxide. Myelin basic protein (MBP) immunohistochemical staining and western blotting were used to detect the expression of cerebral white matter-specific MBP, and changes in myelin structure were observed using transmission electron microscopy. No swelling or necrosis was observed in the corpus callosum of the sham group rats, whereas rats in the model group demonstrated edema, loose structure, fiber disorder, inflammatory gliocytes and selective white matter lesions. Following treatment with miconazole, MBP expression in the corpus callosum was significantly higher compared with the model group. Furthermore, in the model group, myelin sheaths in the corpus callosum were loose with small vacuoles, there was a marked decrease in thickness and structural damage was observed. Conversely, a marked improvement in myelination was observed in the treatment group. The results of the present study suggest that miconazole is able to promote formation of the myelin sheath to ameliorate premature cerebral white matter lesions caused by ischemia or hypoxia in rats.

ZJU-37 Promoted OPC Survival and Myelination in a Rat Neonatal White Matter Injury Model With hOPC Graft 

“…Previous research has shown that the neonatal rat WMI model display decreased motor function and impaired spatial working memory [11,40]. In the present study, we provided in vivo evidence that ZJU-37 combined with hOPCs improved cognitive and motor function compared to ZJU-37 or OPCs alone in WMI rats, as shown by behavioural tests.…”

Mouse Nr2f1 haploinsufficiency unveils new pathological mechanisms of a human optic atrophy syndrome

“…Miconazole and Clobetasol act as two potent inducers of oligodendrocyte differentiation, as they trigger fast maturation of MBP + cells in both physiological and pathological conditions (Najm et al , ; Su et al , ). Given our observations, we asked whether a similar treatment could be of use in the BBSOA mouse model of optic neuropathy.…”

“…This is in accordance with ON hypomyelination at P8, although with different severities between HET and KO , and in HET mutants at P28. Strikingly, postnatal treatment with Miconazole, a potent inducer of oligodendrocyte differentiation in several brain regions (Najm et al , ; Su et al , ), efficiently rescues the myelination grade of Nr2f1 mutants via ERK signaling activation, showing that this chemical drug can counteract hypomyelination in the context of the BBSOA mouse model. This is a first step not only in understanding the pathophysiological features of a complex syndrome, but also in proposing possible therapeutic approaches.…”

Clinical efficacy of gangliosides on premature infants suffering from white matter damage and its effect on the levels of IL‑6, NSE and S100β

“…White matter damage of premature infants is one of the most common causes of cerebral palsy, audiovisual obstacles, intelligence development retardation, epilepsy, learning difficulty and other brain damage syndromes, which seriously influence their quality of life (10). Prior studies have shown that there is a close relation between the occurrence of newborn brain damage and the fetal age (especially related to the low cerebrovascular developmental maturity of premature infants) (11).…”