Development Of A Rat Model For Studying Blast-induced Traumatic Brain Injury And The Neuroprotective Effect Of Emodin On It

Background and ObjectiveWith the development of the science and technology and the use of all kinds of new type weapons, the number of man suffered from explosion is over the man suffered from gunshot during modern war. Explosion is becoming the main type of wound(accounts for the 70%-90% of all wounds).Explosion injury is becoming the research emphasis of modern firearm injury.The main problem in the study of cerebral firearm injury is how to establish an animal model of which the traumatic condition not only corresponds with the reality of clinical craniocerebral trauma but also is observed continuely and can be treated in time.If the survival time of the model is too short,there is no way to study the pathophysiology and pathomorphology of it with more details.To choose the suitable model to do prospective study can futher help increase the clinical remedy level.Now there comes no ideal experimental animal model used for studying blast-induced traumatic brain injury in our world.The spherical explosive has stable dynamite dosage.Its explosion parameter is identified and the explosion detonation energy can be controlled.The spherical dynamite explodes with flexibilite primacord.The detonating point locates at the end of flexibilite primacord at the center of dynamite.The blast wave is spherical and the distribution of pressure field has isotropy.It imitates the blast wave produced by explosion.During detonating the powder burns thoroughly.It does not produce fragments and has no detonation remnants.The animal model established in this experiment can be corresponded with the mechanism of primary effect of the blast wave produced by the explosive weapons.The other interaction factors are shielded successfully and the wound agent is simple.The best advantage of thid model is that it can simulate different degree cerebral explosion injuries through adjusting the dynamite dosage of the spherical explosive(dynamite energy)and changing the distance between the animal and the vulnerating device(vulnerating energy).To produce blast-induced traumatic brain injury animal model,meanwhile,we observed the change of neuron specific enolase (NSE) and traumatic brain edema (TBE)in rat brain tissues after cranio-cerebral explosive wound, observe the protective effects of emodin on the wounded brain.Methods1. To develope a unique rat model to simulate blast effects that commonly occur on the battlefield. An electric detonator with the equivalent of 400 mg TNT was developed as the explosive source. The detonator's peak overpressure and impulse of explosion shock determined the explosion intensity in a distance-dependent manner. Ninety-six male adult Sprague-Dawley rats were randomly divided into four groups: 7.5-cm, 10-cm, 15-cm, and control groups. The rat was fixed in a specially designed cabin with an adjustable aperture showing the frontal, parietal, and occipital part of the head exposed to explosion; the eyes, ears, mouth, and nose were protected by the cabin. After each explosion, we assessed the physiologic, neuropathologic, and neurobehavioral consequences of blast injury. Changes of brain tissue water content and neuron-specific enolase (NSE) expression were detected.2. 78 adult SD rats were randomly divided into three groups: normal contrast group, model group, and emodin treatment group. There were 6 observational time points in each group: 6 h, 12 h, 1 d, 3 d, 5 d, 7 d with 6 rats in each time point. Cerebral blast injury models were produced except normal contrast group, and emodin was given 30 min after wounded (10 mg/kg·d intraperitoneal injection). After explosion, the breathes and behaviors of damaged rats were recorded. Levels of neuron specific enolase (NSE) in the serum and brain water content were measured at different time points. Meanwhile, the numbers of NSE immunohistochemical reactive cells were accounted in the cortex.Results1. The results in 10-cm group show that 87% rats developed apnea, limb seizure, poor appetite, and limpness. Diffuse subarachnoid hemorrhage and edema could be seen within the brain parenchyma, which showed loss of integrity. Capillary damage and enlarged intercellular and vascular space in cortex, along with tattered nerve fiber were observed. These findings demonstrate that we have provided a reliable and reproducible blast-induced TBI model in rats.2. The level of NSE in serum and brain water content of model group and emodin treatment group was obviously higher than pre-injury at most time points (P<0.01), and it reached the peak at 24 h after injury, then, it began to decrease, and still higher than pre-injury at 5 d. The number of NSE immunohistochemical reactive cells in the cortex was significantly decreased. The emodin group has a similar tendency compare with the control group but had an earlier peak time at 12 h after injury and reached normal level at 3 d after injury.Conclusion1. we have developed reliable experimental apparatus for studying cerebral blast injury in a rat model.2. Emodin presents protective effects on wounded brain in rats with cerebral blast injury.