Effects of magnesium sulfate on traumatic brain edema in rats

svarietyofneuroprotectiveagentshavebeensynthesized .However ,besidessomeagentspresentlybeingevaluatedinclinicaltrails ,mostofthesecompoundshavelimitedclinicalusebecauseofneurotoxicityandbehavioralsideeffects .Recently ,severalstudiesdemonstratedthattraumaticinjurytothebraincausesadecreaseinmagnesiumconcentrationcorrelatedwithinjuryseverity .1Sincethen ,moreandmoreattentionhasbeen paidtoMgSO4 foritsneuroprotectiveeffects .Magnesiumsulfatehasbeenwidelyusedinclinicalpracticeforalmost 10 0 years.…     

Neuroprotective effects of nimodipine and MK-801 on acute infectious brain edema induced by injection of pertussis bacilli to neocortex of rats

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Effects of magnesium administration on brain edema and blood-brain barrier breakdown after experimental traumatic brain injury in rats

In this study, we examined the effects of magnesium sulfate administration on brain edema and blood-brain barrier breakdown after experimental traumatic brain injury in rats. Seventy-one adult male Sprague-Dawley rats were anesthetized, and experimental closed head trauma was induced by allowing a 450-g weight to fall from a 2-m height onto a metallic disk fixed to the intact skull. Sixty-eight surviving rats were randomly assigned to receive an intraperitoneal bolus of either 750 micromol/kg magnesium sulfate (group 4; n = 30) or 1 mL of saline (group 2; n = 30) 30 minutes after induction of traumatic brain injury; 39 nontraumatized animals received saline (group 1; n = 21) or magnesium sulfate (group 3; n = 18) with an identical protocol of administration. Brain water content and brain tissue specific gravity, as indicators of brain edema, were measured 24 hours after traumatic brain injury. Blood-brain barrier integrity was evaluated quantitatively 24 hours after injury by spectrophotometric assay of Evans blue dye extravasations. In the magnesium-treated injured group, brain water content was significantly reduced (left hemisphere: group 2, 83.2 +/- 0.8; group 4, 78.4 +/- 0.7 [P <.05]; right hemisphere: group 2, 83.1 +/- 0.7; group 4, 78.4 +/- 0.5. [P <.05]) and brain tissue specific gravity was significantly increased (left hemisphere: group 2, 1.0391 +/- 0.0008; group 4, 1.0437 +/- 0.001 [P <.05]; right hemisphere, group 2, 1.0384 +/- 0.001; group 4, 1.0442 +/- 0.005 [P <.05]) compared with the saline-treated injured group. Evans blue dye content in the brain tissue was significantly decreased in the magnesium-treated injured group (left hemisphere: group 2, 0.0204 +/- 0.03; group 4, 0.0013 +/- 0.0002 [P <.05]; right hemisphere: group 2, 0.0064 +/- 0.0009; group 4, 0.0013 +/- 0.0003 [P <.05]) compared with the saline-treated injured group. The findings of the present study support that beneficial effects of magnesium sulfate exist after severe traumatic brain injury in rats. These results also indicate that a blood-brain barrier permeability defect occurs after this model of diffuse traumatic brain injury, and magnesium seems to attenuate this defect.     

谷氨酸受体拮抗剂在严重烧伤大鼠脑组织中的作用

目的 探讨烧伤后谷氨酸对脑组织的影响及谷氨酸受体拮抗剂的作用。方法 采用30％TBSAⅢ度烧伤大鼠模型,伤后2、6、12和24h测定了脑水含量、脑组织K^ 、Na^ 、Ca^2 、Mg^2 和-氧化氮(NO)代谢产物NO2^-／NO3^-浓度,在光镜和电镜下进行形态学和组织化学研究。结果 烧伤后脑水含量升高,脑组织Na^ 、Ca2^ 、NO2^-／NO3^-浓度高于对照组;脑内ATP酶减少;电镜观察毛细血管内皮细胞、神经细胞及胞浆部分线粒体肿胀,毛细血管壁出现胞饮泡。给予谷氨酸受体拮抗剂D-2-氨基-7-磷庚酸脂(D—AP7),可使脑水含量、脑组织Na^ 、Ca^2 、NO2^-／NO3^-浓度降低,毛细血管壁胞饮泡减少,神经细胞肿胀减轻。结论 烧伤后脑微血管通透性增加、组织细胞有缺血性改变和水肿发生。烧伤后脑组织形态及代谢变化与谷氨酸过量释放有关。兴奋毒性作用通过其受体介导,谷氨酸受体拮抗剂D—AP7可减轻烧伤后脑损伤。     

Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats

Blood-brain barrier (BBB) disruption is a critical event leading to vasogenic brain edema and secondary brain damage after cold injury-induced brain trauma. Matrix metalloproteinases (MMPs), a family of proteolytic enzymes which degrade the extracellular matrix, are implicated in BBB disruption in this model. The purpose of this study was to examine the effects of MMI270 (N-hydroxy-2(R)-[(4-methoxysulfony) (3-picolyl)-amino]-3-metylbutaneamide hydrochloride monohydrate), a synthetic nonspecific MMP inhibitor, on cold injury-induced brain edema in rats. Cold injury was induced by applying a copper probe cooled with liquid nitrogen on the parietal skull for 30 sec in 38 rats. Treatment with MMI270, a bolus injection at a dose of 30 mg/kg, was started immediately after the induction of cold injury and was continued for 24 h at a dose of 40 mg/kg/day using an intraperitoneal osmotic minipump (n = 7). In the untreated control group (n = 7), rats were administered a vehicle and implanted with a vehicle-containing osmotic pump. Two percent Evans Blue (EB) in saline (1 mL/kg) was administrated intravenously immediately after the cold injury in another group of rats, six of which were untreated and six of which were treated with MMI270 at the above dose. At 24 h after the cold injury, the brain water content and the BBB permeability to EB were determined. To assess the protective effect of MMI270 on secondary brain lesion after the cold injury, the MMI270-treated rats received a bolus injection at a dose of 30 mg/kg, followed by a continuous administration of MMI270 for 7 days at a dose of 40 mg/kg/day using an osmotic minipump (n = 6). In the untreated control group (n = 6), the rats were administered the vehicle and implanted with a vehicle-containing osmotic pump. At 7 days after cold injury, the secondary brain lesion was assessed using hematoxylin and eosin (H-E) staining. Compared with the untreated control group, treatment with MMI270 significantly reduced the brain water content in the ipsilateral core and intermediate areas (p < 0.05 and p < 0.01) and protected the BBB integrity to EB in the ipsilateral core area (p < 0.05) at 24 h after the cold injury. The secondary lesion was significantly smaller in the MMI270-treated animals compared with the untreated animals (p < 0.05) a 7 days after the cold injury. O kur results indicate that treatment with MMI270 in rats exhibits protection in acute brain edema formation and secondary brain damage by attenuating the BBB permeability after cold injury.     

Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury

Emerging data suggest that matrix metalloproteinase-9 (MMP-9) plays a critical role in the pathophysiology of brain injury. However, the regulatory mechanisms involved in vivo remain unclear. In this study, we focus on a mitogen activated protein kinase (MAPK) pathway that may trigger MMP-9 after traumatic brain injury. We aim to show that inhibition of the extracellular signal regulated kinase (ERK) would attenuate MMP-9 levels, reduce blood-brain barrier damage, and attenuate edema after trauma induced by controlled cortical impact in mouse brain. Western blots showed that phospho-ERK was rapidly upregulated after trauma. Treatment with U0126, which inhibits MEK, the kinase upstream of ERK, effectively prevented the activation of ERK. After trauma, gelatin zymography showed an increase in MMP-9. U0126 significantly reduced trauma-induced MMP-9 levels. Correspondingly, U0126 ameliorated the degradation of the tight junction protein ZO-1, which is an MMP-9 substrate, and significantly attenuated tissue edema. At 7 days after trauma, traumatic lesion volumes were significantly reduced by U0126 compared with saline-treated controls. These data indicate that the ERK MAPK pathway triggers the upregulation in MMP-9 after trauma, and further suggest that targeting the upstream signaling mechanisms that regulate deleterious MMP-9 activity may reveal new therapeutic opportunities for traumatic brain injury.     

Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies

The biochemical mechanisms mediating delayed or secondary tissue injury after central nervous system trauma remain speculative. We have demonstrated previously that traumatic brain injury in rats causes a rapid decline in tissue intracellular free magnesium [Mg]f and total magnesium [Mg]t concentrations, which were significantly correlated with injury severity. In order to examine the relationship between magnesium and traumatic brain injury, we assessed whether (1) magnesium deficiency exacerbates or (2) magnesium treatment improves posttraumatic outcome following fluid-percussion brain injury (2.0-2.4 atm) in rats. Animals placed on magnesium-deficient diet for 14 days showed a 15% decrease in brain [Mg]f as measured by phosphorus (31P) magnetic resonance spectroscopy (MRS). Magnesium deficiency significantly exacerbated neurologic dysfunction and increased mortality following injury when compared to normally fed saline-treated controls. Conversely, pretreatment with magnesium sulfate (0.1 mEq) 15 min before brain injury prevented the fall in [Mg]f observed by 31P MRS in saline-treated animals and significantly improved both cellular bioenergetic state and chronic posttraumatic neurologic outcome. These combined observations suggest that alterations in brain [Mg]f after trauma may play a role in the pathophysiology of traumatic brain injury.     

Inhibition of Src tyrosine kinase and effect on outcomes in a new in vivo model of surgically induced brain injury

OBJECT: Brain tissue at the periphery of a neurosurgical resection site is vulnerable to injury by a variety of mechanisms including direct trauma, edema, hemorrhage, retractor stretch, and electrocautery. The goal in the present study was to develop an in vivo model of surgically induced brain injury and to test an Src tyrosine kinase inhibitor for neuroprotective properties in this model. METHODS: The authors developed a new surgically induced brain injury model in rats. This model involves resection of part of the frontal lobe. Sprague-Dawley male rats weighing between 300 and 350 g were divided randomly into four groups: Group 1, surgical injury with vehicle treatment; Group 2, surgical injury after treatment with PP1 (an Src tyrosine kinase inhibitor with known neuroprotective properties); Group 3, sham surgery; and Group 4, control. Postoperative assessment included blood-brain barrier (BBB) permeability studies, and histological, immunohistochemical, and Western blot analyses. The authors found that surgical injury caused localized edema and disruption of the BBB compared with findings in the sham surgery group. Treatment with PP1 was associated with decreased edema, decreased breakdown of the BBB, decreased expression of both vascular endothelial growth factor and phosphorylated extracellular signal-regulated kinase 1 and 2, and preservation of ZO-1 expression. CONCLUSIONS: In this study the authors describe a simple and reproducible in vivo animal model of surgically induced brain injury. Pretreatment with PP1 results in improved outcomes in this model, which suggests a possible role for Src tyrosine kinase inhibitors as preoperative therapy for planned neurosurgical procedures.     

An experimental study on the occurrence of brain edema after retrograde cerebral perfusion

To assess the safety of retrograde cerebral perfusion, the occurrence of brain edema after this procedure was investigated. Twenty-eight adult mongrel dogs were divided into three groups that underwent the following treatments: antegrade perfusion (group 1, n=9); retrograde perfusion alone (group 2, n=11); or tetrograde perfusion with drugs (manuitol, thiopental sodium, and methylprednisolone; group 3, n=8). After 90 minutes of cerebral perfusion at 20°C of the pharyngeal temperature, evans blue (EB) was administered to check for disruptions of the blood-brain-barrier (BBB) and brain tissue water content was measured. Intracranial pressure after cerebral perfusion was markedly higher in group 2 than in group 1 (26.4 ± 9.4 vs. 11.2 ± 3.6 mmHg), and brain tissue water content was also significantly higher in group 2 than in group 1 (80.7 ± 2.0 vs. 77.8 ± 0.9%). these data suggested that brain edema was more prominent after retrograde perfusion than after antegrade perfusion. The extent of EB to brain tissue was greater in group 2 than in group 1 (169.8 ± 97.7 vs. 54.7 ± 31.5 μg/dl). The BBB was highly disrupted in group 2 and vasogenic edema appeared after retrograde cerebral perfusion. Maximum intracranial pressure, brain tissue water content and EB concentration were significantly lower in group 3 than in group 2, and did not differ significantly between group 3 and 1. Administration of pharmacologic agents suppressed edema formation and extravasation of EB. We conclude that 90 minutes of retrograde cerebral perfusion at 20°C of the pharyngeal temperature causes brain edema and disrupts the BBB in a manner different from that associated with antegrade perfusion. Mannitol, thiopental sodium, and methylprednisolone prevent these phenomena, indicating that pharmacologic intervention may improve the safety of retrograde cerebral perfusion.     

Mild head injury increasing the brain's vulnerability to a second concussive impact.

OBJECT: Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI. METHODS: Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury. observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta-amyloid or tau were observed in any brain-injured animal. CONCLUSIONS: On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.     

Aquaporin-4 expression in cultured astrocytes after fluid percussion injury

The development of cytotoxic brain edema resulting in increased intracranial pressure is a major cause of death occurring in the early phase of traumatic brain injury (TBI). Such edema predominantly develops as a consequence of astrocyte swelling. We recently documented that fluid percussion injury (FPI) to cultured astrocytes causes cell swelling. Since aquaporin-4 (AQP4) has been strongly implicated in the development of brain edema/astrocyte swelling in various neurological conditions, this study examined the effect of in vitro trauma on AQP4 protein expression in cultured astrocytes. Exposure of astrocytes to FPI resulted in a significant upregulation of AQP4 protein in the plasma membrane due to neosynthesis, as cycloheximide blocked the trauma-induced AQP4 upregulation. Silencing the aqp4 gene by siRNA resulted in a significant reduction in trauma-induced astrocyte swelling, indicating a critical role of AQP4 in this process. We recently documented that oxidative/nitrative stress (ONS), the mitochondrial permeability transition (mPT), and activation of mitogen-activated protein kinases (MAPKs), contribute to trauma-induced astrocyte swelling in culture. We now show that inhibition of these factors reduces the upregulation of AQP4 following trauma. Since TBI has been shown to activate nuclear factor-kappa B (NF-κB), as well as the Na(+),K(+),Cl(-) co-transporter (NKCC), both of which are implicated in brain edema/astrocyte swelling in other conditions, we also examined the effect of BAY 11-7082 and bumetanide, inhibitors of NF-κB and NKCC, respectively, and found that these agents also significantly inhibited the trauma-induced AQP4 upregulation. Our findings show that in vitro trauma upregulates AQP4, and that ONS, MAPKs, mPT, NF-κB, and NKCC are involved in its upregulation.     

Ultrastructural changes in tracheobronchial epithelia following experimental traumatic brain injury in rats: Protective effect of erythropoietin

BACKGROUND: We aimed to demonstrate the time dependent ultrastructural changes in tracheobronchial epithelia after traumatic brain injury. And also, protective effect of erythropoietin was demonstrated. METHODS: We used 56 Wistar-Albino female rats weighing 170 to 200 g. The rats were allocated into 7 groups. First group was the control. The second underwent craniotomy without trauma. The third, fourth, and fifth groups were respectively 2-, 8-, and 24-hour trauma groups. The sixth and seventh groups were respectively treatment (erythropoietin, 1,000 IU/kg) and vehicle (0, 4 ml/rat) groups. Weight-drop method was used for achieving head trauma. Samples were obtained from both trachea and main bronchi. Modified electron microscopic scoring model was used to reveal the ultrastructural changes in both trauma and treatment groups. RESULTS: There was no statistical difference between control and sham groups (p >0.05). Scores of all trauma groups were significantly different from the controls (p <0.05). Trauma produced obvious gradual damage on ultrastructure of the tracheobronchial epithelia. Erythropoietin decreased tracheobronchial scores after traumatic brain injury in significant levels. Erythropoietin attenuated ultrastructural scores for each organelle in significant levels (p <0.05 for each organelle). CONCLUSIONS: The data suggested that ultrastructural damage is obvious at 2 hours deteriorating with time. Erythropoietin protects epithelia against damage after traumatic brain injury. Pharmaceutical lung preservation may help gaining efficacious donor lungs in brain death. But, further time dependent experiments are needed to determine the liability of the donor lung after traumatic brain injury. This fact is to be known for achieving higher graft survival rates.     

脑损伤后不同时间给予高渗盐-羟乙基淀粉液的治疗效应

目的探讨在创伤性脑损伤后不同时间给予高渗盐-羟乙基淀粉液(HSH)对脑损伤的影响。方法选用SD大鼠64只,采用Feeney自由落体损伤模型,于伤后早期(伤后10min)和后期(伤后6h)分别经尾静脉注射HSH、生理盐水(4mg/kg),并据此分为四组,24h后处死动物,干湿重法测定脑组织含水量,伊文氏兰(EB)测定对血脑屏障的影响及应用流式细胞仪测定各组对损伤区周围皮质调亡的影响。结果伤后10minHSH10组的脑组织含水量和EB含量略高于NS10组,而皮层脑细胞调亡数明显低于NS10组(P<0.05);伤后6hHSH6组的脑组织含水量、EB含量和皮层脑细胞调亡数均明显低于NS6组(P<0.05);HSH6组的脑组织含水量、EB含量和皮层脑细胞调亡数均明显低于HSH10组(P<0.05)。结论脑损伤早期给予HSH会加重脑水肿,伤后6h给予HSH不会加重脑水肿;无论伤后早期还是晚期给予HSH均可减少皮层脑细胞调亡数,晚期给药效果更佳。     

硫酸镁对脑外伤后兔血中一氧化氮合成酶动态影响的实验研究

目的探探讨硫酸镁的脑保护作用及对脑外伤后兔血中NOS的动态影响.方法新西兰大白兔40只,随机分为对照组和治疗组(硫酸镁组),采用改良Feeney自由落体脑损伤装置制作重型脑外伤模型,脑外伤后对照组给予甘露醇生理盐水静滴,硫酸镁组则在此基础上给予硫酸镁.分别于伤前(0 h)及伤后3 h、12 h、24h、48 h、72 h、96 h、120h检测血浆NOS.结果重型脑外伤后3小时起,硫酸镁治疗组NOS含量较对照组明显下降.治疗组死亡率比对照组死亡率低.结论硫酸镁在脑外伤后早期(5天内),通过抑制NOS升高而起脑保护作用并降低重型脑外伤的死亡率.     

Effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury

Objective:To study the effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury and the possible mechanism.Methods:The middle degree brain injury in rats was made by BIM-III multi-function impacting machine.The brain mitochondrial respiratory function was measured with oxygen electrode and the ultra-structural changes were observed with transmission electron microscope(TEM).Results:1.The brain mitochondrial respiratory stage III and respiration control rate reduced significantly in the untreated groups within 24 and 72 hours.But treated Group A showed certain degree of recovery of respiratiory function;treated Group B showed further improvement.2. Untreated Group,treated Groups A and B had different degrees of mitochondrial ultra-structural damage respectively, which could be attenuated after the treatment with magnesium sulfate.Conclusions:The mitochondrial respiratory function decreases significantly after traumatic brain injury.But it can be apparently improved after magnesium sulfate management along with the attenuated damage of mitochondria discovered by TEM.The longer course of treatment can obtain a better improvement of mitochondrial respiratory function.     

Evaluation of a novel calcium channel blocker, (S)-emopamil, on regional cerebral edema and neurobehavioral function after experimental brain injury.

The authors investigated the effects of a novel calcium channel blocker, (S)-emopamil, on cerebral edema and neurobehavioral and memory function following experimental fluid-percussion brain injury in the rat. Two independent experiments were performed to evaluate the effects of this compound on cardiovascular variables and postinjury cerebral edema (increases in tissue water content), and on cognitive deficits and neurological motor function following brain injury. Treatment with (S)-emopamil significantly reduced focal brain edema at 48 hours after brain injury. Profound memory dysfunction induced by brain injury was significantly attenuated following (S)-emopamil treatment. In addition, (S)-emopamil also attenuated the deficits in motor function that were observed over a 2-week period following brain injury. These results suggest that changes in calcium homeostasis may play an important role in the pathogenesis of trauma to the central nervous system and that the calcium channel blocker (S)-emopamil might be a useful compound for the treatment of traumatic brain injury.     

Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury

OBJECT: Cytidine 5'-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI. METHODS: After anesthesia had been induced in Sprague-Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet-dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight-10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5'-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/ kg of CDPC significantly decreased brain edema and BBB breakdown. CONCLUSIONS: This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.     

Effect of AVP on brain edema following traumatic brain injury

Objective: To evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema. Methods: A total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS≤8) and moderate traumatic brain injury group ( MTBI, GCS >8). Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group) and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan. Results: plasma AVP levels (ng/L) were (mean±SD): control, 3. 06±1. 49; MTBI, 38. 12±7. 25; and STBI, 66. 61±17. 10. The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P<0. 01). And the AVP level was correlated with the severity (STBI r =0.919, P < 0.01; MTBI r = 0.724, P < 0.01) and the duration of brain edema (STBI r = 0. 790, P < 0. 01; MTBI r = 0. 712, P<0.01). Conclusions: The plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.     

Interstitial photoradiation injury of normal brain.

The effect on normal brain of continuous interstitial laser irradiation at 630 nm through an implanted cylindrical-shape, diffusion-tipped optical fiber was studied in the rat. Brain water content in the laser irradiation area (LIA) and Evans blue (EB) dye content in selected areas of the brain were measured for different laser power outputs from 0 to 250 mW after 5 minutes of photoradiation. The degree and nature of tissue damage was examined histologically and correlated with the laser power level. There is significant brain damage, blood brain barrier (BBB) disruption, and brain edema in LIA for laser power outputs in excess of 100 mW from the diffusion tip (p less than 0.001). Brain edema in the LIA is strongly correlated with BBB disruption indicated by the presence of EB. Histologically, the cortical surface was more susceptible than deeper white matter regions to interstitial laser irradiation. Possible indirect mechanisms of brain injury from interstitial laser irradiation are discussed.     

Lubeluzole following traumatic brain injury in the rat.

Lubeluzole, a novel nitric oxide synthase (NOS) pathway modulator, was shown to be neuroprotective in cerebral ischemia as studied in animal models and clinical trials. The present study investigated the effect of lubeluzole on contusion volume and brain edema following traumatic brain injury. Sprague-Dawley rats (n = 36) were subjected to cortical impact injury. Lubeluzole (0.8 mg/kg i.v.; n = 18) or a corresponding volume of vehicle (n = 18) was injected 15 and 75 minutes following trauma. Animals were sacrificed 24 hours following trauma. Contusion volume was measured planimetrically from coronal slices stained with hematoxylin and eosin. In this group, T2-weighted magnetic resonance imaging (MRI) was also performed 90 minutes and 6 and 24 hours after trauma. Hemispheric swelling and water content were determined gravimetrically 24 hours after trauma. In this group, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were monitored for 30 minutes before sacrifice. Lubeluzole did not reduce contusion volume, hemispheric swelling, or water content. ICP, MABP, and the resulting CPP did not differ between treated and untreated rats 24 hours after injury. T2-weighted MRI revealed a higher volume of edema at 90 minutes after trauma in treated rats. However, at 6 and 24 hours after trauma, no significant difference was discernible. Under these experimental conditions, lubeluzole fails to exert beneficial effects following experimental traumatic brain injury (TBI).