| Background and ObjectiveWhite matter damage in preterm children(especially for 23 weeks-32 weeks of gestation) is the main form of brain damage, mainly as periventricular white matter lesions(PWMD), also known as periventricular leukomalacia(PVL), often left with varying degrees sequelae, including cerebral palsy and cognitive dysfunction.Currently neonatal hypoxic-ischemic encephalopathy(HIE) lack of specific treatment.Melatonin(melatonin, MT) is a pineal gland hormone indole amines, having a high affinity for the central nervous system, easily through the blood-brain barrier. In recent years, found that exogenous melatonin have the prevention and protection on neonatal brain damage caused by hypoxic-ischemic(Hypoxia-ischaemic, HI). At present, the domestic research on MT of neonatal brain injury affects mainly focused on neurons in the gray matter of the brain, the impact of MT PWMD of immature brain has not been reported; abroad, other studies by Nicola J.Robertson showed that the protective effect of melatonin enhances hypothermia on HIE, mechanisms for improving cerebral energy metabolism and inhibition of apoptosis thalamus, basal ganglia and white matter cells. In preterm children, especially 23 weeks-32 weekspremature white matter in children, mainly O4-positive cells are oligodendrocytes that oligodendrocyte precursor cells(OPC), which is preterm children PWMD main target cells. OPC after HI injury, apoptosis, leading to reduction in the number of preterm children PWMD mechanism is an important part. And for MT on PWMD the OPC apoptosis, the number and the impact on long-term white matter myelination at home and abroad are not reported. In this study, PWMD neonatal rat model for the study of this issue discussed to HI-induced premature children PWMD provide a possible method of treatment.Materials and Methods48 healthy 3-day-old clean grade S-D(Sprague-Dawley) rats, weighing 6-9g,male or female, randomly divided into: sham group(SHAM group),hypoxia-ischemia group(HI group) intervention group and melatonin(HI+MT group)were 16( n = 16).SHAM group: only blunt dissection of the left common carotid artery, but not for subsequent ligation and hypoxia;HI Group: First blunt dissection and ligation of newborn rats the left common carotid artery, one hour after the back side maternal, newborn rats into the anoxic compartment made of plexiglass, filled with nitrogen-oxygen mixture(94 % N2,6%O2), time is 2 hours;HI+MT groups: before surgery, after surgery, after surgery 1 hour and 24 hours after surgery, respectively, according to 10 mg / kg intraperitoneal injection of melatonin solution(10mg MT dissolved in ethanol 5ml, 95 ml of normal saline was added, now with the existing), SHAM group, HI group at the same time point were injected volume of the solvent.The rats reared to P5(the day of birth recorded as P1) when 8 in each group were randomly taken by ether inhalation, after moderate anesthesia, from the left ventricle has about 40 m L saline infusion and about 40ml40 g / L of formaldehyde then craniotomy brain, and then fixed 24 ~ 48 h under 40 g / L formaldehyde at room temperature, followed by dehydration and transparent, and then embedded in paraffin,then slice, slice thickness take 3μm, HE staining, O4 immunohistochemistry,Caspase-3 immunohistochemistry brain microstructure all rats, O4-positive cells and the number of cases the expression of Caspase-3; each group after another eight to P17 when anesthetized with ether, as described above sliced, OK HE staining and immunohistochemistry MBP lateral expansion of the situation and MBP expression situation.Results1 2-day-post-operation white matter around the brain ventricles SHAM group operated side was normal, clear staining; HI group structure loose fiber disorder,visible malacia; HI+MT group between the first two groups, O4 positive cells in the SHAM group(76.418±7.333), HI+MT group(58.359±14.571), HI group(43.647±12.887) in order to reduce the difference is statistically significant(P <0.05);the expression of Caspase-3 in the SHAM group(105.627±31.745), HI+MT group(146.329±34.181), HI group(198.337±57.738) sequentially increased, the difference is statistically significant(P <0.05);2 14-day-post-operation the cerebral white matter surgical ventricular lateral ventricle index in SHAM group(0.988±0.236), HI+MT group(1.793±0.418), HI group(2.746±0.678) in order to increase, MBP photometric values in turn decrease(respectively 38.738±9.416,22.832±5.933,13.469±3.729).ConclusionsMelatonin can be caused by a hypoxic ischemic injury in immature white matter play a protective role;the protective effects may be by inhibiting apoptosis of oligodendrocyte precursors, and increase the number of remaining pre-oligodendrocytes body, thus improving brain during the development of white matter myelination. |
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