Establishment Of Acute Subdural Hematoma In Modified Rat Model And Experimental Study Of Its Natural Course

Objective To improve and establish a stable and efficient acute subdural hematoma rat model and explore the relative pathophysiological mechanism during this dynamic change of hematoma absorption.Methods The experiment used 150 adult male Wistar rats which were randomly divided into 2 different modeling groups.There were 5 injury control rats and 20 modeling rats in traditional modeling group. Based on traditional model, the craniotomy, subdural imbedding metal needle under micromanipulation and sealing the position before subdural injection using 300μl non-heparinized autologous blood. Then the integral brain was detached for HE staining to observe the pathological features of the hematoma after sacrifice on day 2 and 6.There were 5 injury control rats and 120 modeling rats in modified modeling group. The modified model used drilled craniotomy and bone imbedding with vinyl plastic catheter. Behavioral tests were assessed to evaluate neurological deficits before blood induction and during a two week follow up period and magnetic resonance imaging was used to observe the dynamic change of hematoma; Then the integral hematoma was detached for HE staining to observe the histomorphological features of the hematoma, neomembrane and cortex on 2nd,4th,6th,8th,10th,14th day (n=20/group); The dynamic changes of the hematoma and cortex and the pathological characteristics of neovascularization was detected through CD31 immunohistochemistry method and transmission electron microscope observation.Results The modified model was associated with mean percentage success of 73.33%(88/120), failure of 11.67%(14/120) and the mortality of 15.00%(18/120) versus the traditional model was 15.00%(3/20),55.00%(11/20) and 30.00%(6/20) respectively. All animals with subdural hematoma had severe sensorimotor deficits immediately after surgery, but showed signs of improvements over the follow up period. In successful modeling rats, blood clots were covered with hyperblastosis and there were many infiltrated inflammatory cells and vascular sinusoidal channels in early stage after modeling(≤4d)without significant changes of the neovascularization(P>0.05);Then the newly formed channels were gradually mature and the microvessel density significantly increased compared with day 2(P< 0.05)and achieved to the peak at 8 day after operation; Finally, the microvessel density declined to the baseline level paralleling to the degeneration of the neomembrane.The change of hematoma showed a non-linear reduction which was significantly accelerated on day 8 after surgery (P<0.01)and the hematoma finally disappeared on day 14.The volume of hematoma was closely correlated with the neomembrane neovascularization (r=-0.750,P=0.000).In contrast,hematoma was disappeared earlierly and damage on cortex was severe in failure modeling rats without formatting the typical neomembrane. There was no obvious damage in cortex in control groups using these two different modeling methods.Conclusion The improved model seems simple, reproducible and higher successful rate comparing with traditional modeling groups.The original injury in rat modeling plays critical roles in the result of successful model or not. The formation of neomembrane and the neovascularization in neomembrane play critical roles in the hematoma absorption. Successfully modeling rats associated with definite behavioral features and hematoma structural characteristic.The improved subdural hematoma rat model should be useful in elucidating the relative factors during its dynamic change.