| Hypoxic-ischemic brain damage(HIBD) resulted from birth asphyxia remains a common causes leading to acute mortality and chronic neurological disability in survivors. Few therapeutic interventions are available for clinical use. Currently experimental cerebral protective interventions for HIBD including pharmacologic agents (for examples: antagonists of excitatory amino acids, calcium channel Mocker, free-radical scavengers, NO synthase inhibitor) but the result was unsatisfactory.In 2000, German scientist Burmester first reported that Neuroglobin (Ngb), Which is protein related to myoglobin and hemoglobin but expressed predominantly in the brain, It was induced by neuronal hypoxia and cerebral ischemia and protected against hypoxic or ischemic neuronal injury. Neuroglobin provides a new idea and sets off review and interesting on neuronal hypoxia in the international context. The central nervous system is particularly susceptible to low-oxygen conditions (hypoxia) that occur under cerebral ischemia, and a reduced supply of oxygen to the brain will inevitably lead to death of the neurons. There were increasing evidences showing that an enhanced expression of neuroglobin can help to sustain cellular respiration would increase the likelihood of neuronal survival under hypoxia and on ischemic injury. Neuroglobin may be involved protective reaction in the cerebral hypoxia.Moderate hypothermia referred to a slight lowering of body temperature (2-6℃) through artificially induced method which in turn produce a marked protection against hypoxic-ischemic damage in central neurons, in 1987, Busto first proposed the concept of mild hypothermia (32-33℃)of brain protection. Many researches found that mild hypothermia can protect local cerebral ischemia and cerebral ischemia. This non-specific and widely affecting manner plus its simple carrying-out, safety and economy might explain why hypothermia is superior to any medicine developed. But hypothermia reduce cerebral edema, inhibit inflammation, Stabilize blood-brain barrier, such as cerebral protection and stability to the exact mechanism is still not clear.Objectives To investigate the expression of neuroglobin after hypoxic-ischemia brain damage in neonatal rats in mild hypothermia and study the cerebral protective mechanism of mild hypothermia.Method One hundred twenty wistar rats of 7 days old were divided into: sham-operated group (n=20), normal temperature hypoxic-ischemia brain damage group (n=50) and mild hypothermia hypoxic-ischemia brain damage group (n=50) randomly. Normal temperature group and mild hypothermia group were divided into 5 subgroups respectively. It was 1, 5,15, 30, 60 minutes after the establishment of rat model, There were 10 neonatal rats in each subgroups. The rat model of brain damage was established by ligaturing bilateral common carotid arteries. The rectal temperature (T_R) of normal temperature group were controlled at range 36-37℃and that of mild hypothermia group were controlled at range 32-33℃.Expression of neuroglobin in the brain tissues was detected by reverse-transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, in order to evaluate whether the level of expression and/or the distribution of neuroglobin is influenced by short-term hypoxia, with particular focus on the Cerebral Cortex in mild hypothermia group.Result In hypothermia group, the expression of neuroglobin mRNA on 1, 5,15, 30min(A: 1.10±0.05, 0.96±0.06, 0.79±0.06, 0.67±0.08) was significantly increased compared with that of the normal temperature group (A :0.98±0.07, 0.81±0.11,0.53±0.08, 0.36±0.04) (P<0.05) after ischemia. The immunohistochemistry suggested that the integral optical density of neuroglobin on 5,15, 30min in hypothermia group, IOD:(23. 26±2.83,32.06±2.58,19.39±3.16)x10~5 was significantly increased compared with that of the normal temperature group, IOD: (19.16±2.16, 25.15±4. 05,13. 78±2. 40) x10~5, (P<0. 05).Conclusion The expression of neuroglobin is more strong in brain tissue and retain a longer period of time after hypoxic-ischemia brain injury of newborn rats, It suggested that it may be one of the cerebral protective mechanism of mild hypothermia increases the expression of neuroglobin. |
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