| Backgroud and Objective: Brain edema is a kind of the most common and serious secondary damage after craniocerebral injury, and is also one of important reasons resulting in death and disability of patients with craniocerebral injury. Traumatic brain edema includes cytotoxicity edema and vasogenic edema,but the protecting blood brain barrier (BBB) and alleviating vasogenic brain edema after injuries are more attractive topic in treatment of traumatic brain injury patients because vasogenic brain edema play an important role in traumatic brain edema formation, high intracranial pressure and secondary brain damage. Propofol can reduce cerebral blood flow, decrease intracranial pressure (ICP), and decrease cerebral metabolic requirement for oxygen (CMRO2),and produce the neuropeotective effects in ischemic brain injury,but the study on the influence of propofol on traumatic brain injury is little so far. Therefore, in this study, the effects of propofol on vasogenic brain edema and delayed neuronal apoptosis were explored after brain injury in rats by using a classic model of vasogenic brain edema in order to provide new gists for clinical application of propofol in craniocerebral injury patients. Methods : 1. The animal model of vasogenic brain edema was established by freezer (pre-cold in liquid nitrogen with the temperature at -196℃)-induced brain injury in Wistar rats on the left parietal side of skull of rat for 1 min. 2. Health male Wistar rats were randomly divided into sham-operation groups, brain injury groups treated with saline, brain injury groups with propofol. Propofol was injected intraperitoneally at a dose of 100mg/kg which is equivalent to clinical dose for general anesthesia:50mg/kg propofol was administered ip 15min after brain cold injury, and again with the same dose at 30min after the first injection.Rats were sacrificed at 2, 6, 24 hours after brain cold injury. 3. The permeability of BBB was evaluated by the Evans Blue extravasation methods. 4. The expression of MMP9 mRNA in the rat brains was assayed by RT-PCR technique. 5. The expression of MMP9 protein in the rat brains was detected by immuno-histochemistry,and the pathomorphological changes in brain tissue was observed by HE staining . 6. Brain water content was determined by comparison of wet and dry weight, and MDA content in brain tissue was measured. 7. Apoptosis of neural cells was detected by TUNEL methold and Neurological severity score (NSS) was evaluated 24 hours after brain injury. Results: 1. The extravasation of EB in the ipsilateral intermediate brain area(left side) in groups treated with saline at each time point was significantly higher than that in sham-operation group (Ρ< 0.01), and it reached the peak at 6~24h. The extravasation of EB in the ipsilateral intermediate brain in groups treated with propofol were significantly lower than that in groups treated with saline at 6h and 24h , respectively(Ρ<0.05,Ρ< 0.01). The extravasation of EB in the contralateral brain has no significant change . 2. Brain water content in the ipsilateral intermediate cortex in groups treated with saline at each time point was significantly higher than that in sham-operation group (Ρ< 0.01), and it reached the peak at 24h. Brain water content in groups treated with propofol was significantly lower than that in group treated with normal saline at 6h and 24h , respectively(Ρ<0.05, Ρ< 0.01). Brain water content in the contralateral brain has no significant change . 3. MDA content in brain tissue in group treated with saline were significantly higher than that in sham-operation group at 2 , 6 and 24h ,respectively(Ρ< 0.01). At each time point, MDA content in brain tissue in groups treated with propofol was significantly lower than that in groups treated with saline(Ρ<0.05,Ρ< 0.01,Ρ< 0.01). 4. There was obvious necrosis inside the cold lesion and edema in the cortex surrounding the cold lesion at each time point after cold injury. Compared with groups treated with saline, the pathomorphological change in brain tissue was alleviated evidently in groups treated with propofol. 5. The expression of MMP9 mRNA was weak in the rat brains of sham-operation groups. The expression of MMP9 mRNA increased significantly following cold injury with the peak at 6h. Compared with groups treated with saline, the expression of MMP9 mRNAdecreased significantly in groups treated with propofol at 6h and 24h, respectively(Ρ<0.05, Ρ< 0.01) 6. There was no evident MMP9 protein expression in sham-operation groups. Brain cold injury induced markedly MMP9 protein expression with the peak at 6h. Compared with groups treated with saline, the expression of MMP9 protein decreased significantly in groups treated with propofol at 6h and 24h, respectively(Ρ<0.05, Ρ< 0.01). 7. TUNEL positive cells were hardly observed in the analogous areas in the contralateral hemisphere and in sham-operation groups. A few TUNEL positive cells were detected in the periphery of cortex surrounding the cold lesion in groups treated with saline at 24h.Compared with groups treated with saline, apoptosis index decreased significantly in groups treated with propofol at 24h(Ρ<0.05). 8. Neurological disfunction was observed after brain cold injury. Compared with groups treated with saline, Neurological severity score (NSS) decreased significantly in groups treated with propofol at 24h(Ρ<0.05). No neurological disfunction was observed in sham-operation groups. Conclusion: 1. The model of vasogenic brain edema by cold injury in rats was succeeded, and vasogenic brain edema appeared at the early time after brain injury. 2. It was obvious that delayed neuronal apoptosis as well as neurological disfunction after brain injury in rats occurred. 3. The overproducing of free radicals and the increasing of MMP9 expression may contribute to vasogenic brain edema formation and secondary injury following brain injury. 4. Propofol at the clinical dose for general anesthesia may lighten vasogenic brain edema, reduce delayed neuronal apoptosis and improve neurological disfunction by decreasing lipid peroxidation and MMP9 expression after brain injury. |
