Experimental Study On Intracranial Venous Circulatory Disturbance Promoting Damage Of TBI Rats

Objective: Based on laser speckle(LSCI)and magnetic resonance technology,using animal models to observe the changes of cerebral cortex blood flow(CBF)under pressing of traumatic acute subdural hematoma(ASDH)before and after hematoma removal during craniotomy.To explore the effects of changes in intracranial venous circulation secondary to TBI and decompression craniotomy on cerebral blood flow.With making a composite animal model of ASDH and cranial venous venous-outflow obstruction(CVO),to study the pathological mechanism of CVO impairment aggravating damage after trauma from the perspective of imaging and molecular biology,and then reveal the relationship between CVO and neuroinflammation as well as tissue swelling after trauma,providing guidance for clinical treatment.Methods: Firstly,we characterize the anatomical structure of the rat cerebral venous circulation using LSCI,MR vein and vascular reconstruction techniques,and clarify the way that cerebral veins flow out of the cranial cavity in rats.According to the characteristics of intracranial veins of rats,the venous plexus at the left posterior orbital venous plexus and the left petrous hiatus were ligated to form CVO model.The changes in local CBF after obstruction were dynamically observed through LSCI,establishing a theoretical foundation for the next experiment.Secondly,the ASDH rat model was created following the modified Miller method,the high-resolution two-dimensional cerebral cortex blood flow map was obtained by LSCI,the full-field change characteristics of the CBF were observed dynamically.The situation of deep brain venous return of ASDH rats were observed by the magnetic resonance SWI sequence.Combining with intracranial pressure and blood pressure changes,we analyze the influence of ASDH on the characteristics of blood flow parameters in blood vessels.Thirdly,LSCI was used to monitor the dynamic changes of local cerebral blood flow during hematoma removal by simulating the craniotomy in ASDH rats.Comparing to the sham operation group,the changes in cortical arteriovenous and microcirculation compliance before and after hematoma compression were explored.To reveal the internal connection between cerebral venous circulation and intraoperative brain swelling,and to better understand the mechanism of ischemia-reperfusion injury.Finally,on the basis of ASDH animals,intervention of CVO was given to form a composite model.The sham operation group(Sham),CVO group,ASDH group,and ASDH+CVO group were constructed respectively.Neurobehavioral evaluation and determination of brain water content were performed,as well as Evans blue staining and determination of content.Immunofluorescence,Elisa experiment and Western blot were used to detect the expression of inflammatory factors and the expression levels of metalloproteinases ADAM17 and MMP9.The rats in the ASDH+CVO group were intervened with XPro1595 to compare the changes of NF-?B/MMP9 pathway before and after the inhibition of sol TNF.The pathological mechanism of intracranial venous circulatory disorders which aggravated brain tissue damage after trauma was studied from the perspective of imaging and molecular biology.Results: Through the application of LSCI and MRI vascular reconstruction technology in the brain imaging of rats,the intracranial veins of rats mainly return by the external jugular vein.The front of the superior sagittal sinus is not occluded,passing through paired rostral rhinal veins which located on the junction of the telencephalon and the olfactory brain.The veins are connected to the orbital venous plexus on both sides.The back end is connected to the petrosquamous sinus,draining into the posterior facial vein of the external jugular venous system.Ligating the venous plexus at the posterior orbital venous plexus and the venous plexus at the petrous hiatus on one side of the rat can block the intracranial venous-outfolw of local brain.The intracranial hypertension caused by ASDH made blood circulation disorders of cerebral cortex veins on the oppressed and contralateral.The relationship between cerebral venous blood flow and intracranial pressure was not a simple linear correlation.During ASDH craniotomy,compared with the blood flow velocity in arteries and capillaries,the recovery of cortical venous blood flow was delayed.CVO aggravated the neurological deficit in ASDH rats,damaged the blood-brain barrier,decreased the content of tight junction proteins ZO-1 and Occludin between vascular endothelial cells,increased the expression of MMP9,and promoted the increase of the expression level of ADAM17.The intracranial cells were mainly located in microglial cells or macrophages(Iba-1 positive),and led to increased secretion of sol TNF.The activation of the sol TNF/NF-?B/MMP9 pathway resulted in subsequent neuroinflammation and damage.Conclusion: Intracranial hypertension secondary to TBI can cause disorders of cortical venous circulation;CVO promotes the increase of the expression of ADAM17 which caused by immune cells,leading to increased secretion of sol TNF and activation of downstream NF-?B/MMP9 pathways.The activation of sol TNF/NF-?B/MMP9 pathway aggravates neuroinflammation and swelling of brain after TBI.Changes in the functional status of cerebrovascular may be the basis of secondary brain injury.The treatment strategy should shift from simply emphasizing the goal of improving cerebral perfusion to promoting the dynamic balance of the vasculature.