1.Incomplete Protective Effects Of Minocycline On Traumatic Brain Injury In Rats And Mice 2.Distinct Roles Of Cysteinyl Leukotriene Receptor Type 1 And Type 2 In Oxygen Glucose Deprivation-induced PC12 Cell Death

Traumatic brain injury is a common cause for the mortality and disability in adults. Up to date, there are no effective therapeutic drugs for clinical treatment of traumatic brain injury. Minocycline, a semisynthetic tetracycline derivative, can pass through brain-blood barrier. It has been reported that minocycline has neuroprotective effect against brain ischemia and anti-inflammatory effects. It can inhibit the activation of microglia cells and the excitotoxicity in the brain. It also inhibits apoptosis-related caspase-1 and caspase-3 expression, as well as inducible NOS and p38 MAPK. Minocycline exerts neuroprotective effect on central nervous degenerative disorders such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis;it also protects against spinal cord injury, brain ischemic injury and the injury in intracerebral hemorrhage. In addition, evidence shows that minocycline has neuroprotective effect on closed head traumatic injury in mice.Experimental traumatic brain injury model is designed to reliably and validly reproduce the clinical sequelae of traumatic brain injury, but there is still no model can precisely mimic the human traumatic brain injury. Thus, to systemically evaluate the neuroprotective effect of minocycline on traumatic brain injury, we used three experimental traumatic brain injury models, rat weigt-drop traumatic injury, mouse closed head traumatic injury and mouse cold-induced brain injury. Minocycline (45mg/kg, ip) was administered twice daily for 2 d before the operation, 30 min before and 1 h after the operation, and once daily for 2 d following the operation (totally 8 doses in 5 days). After the operation, the behavioral alteration was observed daily, lesion area and survival neuron density were measured at the end of the experiments (14 d after the injuries).For rat weight-drop traumatic injury, the injury induced obvious neurological dysfunction, brain edema and neuron loss. Minocycline promoted the recovery of hindlimb motor activity (inclined board angle) and inhibited the enlargement of the injured hemisphere (indicating the inhibition of brain edema), but did not alter the other indexes. For mouse closed head traumatic injury, the injury decreased the survival neurons in the hippocampus and cortex, caused learning and remember disturbance in a step through test, but did not cause obvious neurological dysfunction. Minocycline reduced the neuron loss and improved the learning and remember ability. For mouse cold-induced brain injury, the injury was relative small and did not cause any neurological change and learning and remember disturbance;but the injury induced obvious morphological disturbance in the cortex. Minocycline reduced the death rate and the lesion area after cold-induced injury, but did not inhibit the neuron loss within the lesion area.Thus we conclude that minocycline has incomplete neuroprotective effects on three different models of traumatic brain injury in rats and mice. Due to the differences in animal species, injury severity and compensation after injury, each traumatic brain injury model has its own characteristics and minocycline exhibits different efficacies in the three models.