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.     

Attenuation of brain edema, blood-brain barrier breakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-D-aspartate receptor antagonist, after experimental traumatic brain injury in rats

OBJECTIVE: Traumatic brain injury (TBI) has been shown to induce a significant change in polyamine metabolism. Polyamines and polyamine-dependent calcium influx play an important role in mediating the effects of excitotoxic amino acids at the N-methyl-D-aspartate (NMDA) receptor site. We studied the effects of ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, on brain edema formation, blood-brain barrier breakdown, and volume of injury after TBI. METHODS: Experimental TBI was induced in Sprague-Dawley rats by a controlled cortical impact device, functioning at a velocity of 3 m/s to produce a 2-mm deformation. Ifenprodil or saline (10 mg/kg) was injected intraperitoneally immediately after the cortical impact injury and then every 90 minutes until 6 hours after TBI. Blood-brain barrier breakdown was evaluated quantitatively 6 hours after injury by fluorometric assay of Evans blue extravasation. Brain water content, an indicator of brain edema, was measured with the wet-dry method 24 hours after TBI. Injury volume was quantitated from the brain slices stained with 2% cresyl violet solution 7 days after TBI. RESULTS: Blood-brain barrier breakdown was significantly lower in the traumatic cortex of the ifenprodil-treated group than in the saline-treated group (84.4 +/- 26.8 microg/g versus 161.8 +/- 27 microg/g, respectively, P < 0.05). Brain edema was significantly reduced in the cortex of the ifenprodil-treated group relative to that in the saline-treated group (80.9 +/- 0.5% versus 82.4 +/- 0.6% respectively, P < 0.05). Ifenprodil treatment reduced injury volume significantly (14.9 +/- 8.1 mm3 versus 24.4 +/- 6.7 mm3, P < 0.05). CONCLUSION: The polyamine-site NMDA receptor antagonist ifenprodil affords significant neuroprotection in a controlled cortical impact brain injury model and may hold promise for the discovery and treatment of the mechanism of delayed neurological deficits after TBI.     

Ghrelin prevents disruption of the blood-brain barrier after traumatic brain injury

Significant effort has been focused on reducing neuronal damage from post-traumatic brain injury (TBI) inflammation and blood-brain barrier (BBB)-mediated edema. The orexigenic hormone ghrelin decreases inflammation in sepsis models, and has recently been shown to be neuroprotective following subarachnoid hemorrhage. We hypothesized that ghrelin modulates cerebral vascular permeability and mediates BBB breakdown following TBI. Using a weight-drop model, TBI was created in three groups of mice: sham, TBI, and TBI/ghrelin. The BBB was investigated by examining its permeability to FITC-dextran and through quantification of perivascualar aquaporin-4 (AQP-4). Finally, we immunoblotted for serum S100B as a marker of brain injury. Compared to sham, TBI caused significant histologic neuronal degeneration, increases in vascular permeability, perivascular expression of AQP-4, and serum levels of S100B. Treatment with ghrelin mitigated these effects; after TBI, ghrelin-treated mice had vascular permeability and perivascular AQP-4 and S100B levels that were similar to sham. Our data suggest that ghrelin prevents BBB disruption after TBI. This is evident by a decrease in vascular permeability that is linked to a decrease in AQP-4. This decrease in vascular permeability may diminish post-TBI brain tissue damage was evident by decreased S100B.     

Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury

Objective：To explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier （BBB） in rats following traumatic brain injury （TBI）.Methods： A total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups：sham-operation,TBI and Xingnaojing injection was set up by the improved device of Feeney＇s weightcontent and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery.Results： In sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%±1.22%and 5.13μg±0.71μg. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days （83.49%±0.54%, 82.74%±0.72%, 80.22%±0.68%, 79.21%±0.60%）, being significantly higher than that in sham operation group （P〈0.05）. Evans blue content was increased in TBI group （16.54 μg±0.60 μg, 14.92μg±0.71μg, 12.44 μg ±0.92μg, 10.14μg±0.52 μg） as compared with sham-operation group（P〈0.05）. After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group （81.91%±1.04%, 80.38%±0.72%, 79.54%±0.58%,78.60%±0.77%, P〈0.05）. Xingnaojing injection also reduced the leakage of BBB as compared with TBI group （15.11 μg± 0.63 μg, 13.62 μg±0.85μg, 10.06 μg±0.67 μg, 9.54 μg±0.41 μg,P〈0.05）.Conclusion： Xingnaojing injection could alleviate cerebral edema following TBI via reducing permeability ofBBB.     

Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury

Objective:To explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier (BBB) in rats following traumatic brain injury (TBI).Methods: A total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups:sham-operation,TBI and Xingnaojing injection was set up by the improved device of Feeney's weightcontent and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery.Results: In sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%±1.22%and 5.13μg±0.71μg. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days (83.49%±0.54%, 82.74%±0.72%, 80.22%±0.68%, 79.21%±0.60%), being significantly higher than that in sham operation group (P<0.05). Evans blue content was increased in TBI group (16.54 μg±0.60 μg, 14.92μg±0.71μg, 12.44 μg ±0.92μg, 10.14μg±0.52 μg) as compared with sham-operation group(P<0.05). After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group (81.91%±1.04%, 80.38%±0.72%, 79.54%±0.58%,78.60%±0.77%, P<0.05). Xingnaojing injection also reduced the leakage of BBB as compared with TBI group (15.11 μg± 0.63 μg, 13.62 μg±0.85μg, 10.06 μg±0.67 μg, 9.54 μg±0.41 μg,P<0.05).Conclusion: Xingnaojing injection could alleviate cerebral edema following TBI via reducing permeability ofBBB.     

Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury

Objective:To explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier (BBB) in rats following traumatic brain injury (TBI).Methods: A total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups:sham-operation,TBI and Xingnaojing injection was set up by the improved device of Feeney's weightcontent and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery.Results: In sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%±1.22%and 5.13μg±0.71μg. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days (83.49%±0.54%, 82.74%±0.72%, 80.22%±0.68%, 79.21%±0.60%), being significantly higher than that in sham operation group (P<0.05). Evans blue content was increased in TBI group (16.54 μg±0.60 μg, 14.92μg±0.71μg, 12.44 μg ±0.92μg, 10.14μg±0.52 μg) as compared with sham-operation group(P<0.05). After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group (81.91%±1.04%, 80.38%±0.72%, 79.54%±0.58%,78.60%±0.77%, P<0.05). Xingnaojing injection also reduced the leakage of BBB as compared with TBI group (15.11 μg± 0.63 μg, 13.62 μg±0.85μg, 10.06 μg±0.67 μg, 9.54 μg±0.41 μg,P<0.05).Conclusion: Xingnaojing injection could alleviate cerebral edema following TBI via reducing permeability ofBBB.     

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier

Background

Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).

Methods

CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.

Results

Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).

Conclusions

PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.     

地西泮对放射性脑损伤大鼠血脑屏障的影响

目的研究照射前给予地西泮对放射性脑损伤大鼠血脑屏障的影响,探讨其对放射性脑损伤的防护作用机理。方法 240只SD大鼠随机分为4组,每组60只,D-R组:照射前30 min腹腔注射地西泮5 mg／kg;N-R组:照射前未用药;D-SR组:假照射(放置于照射野之外)前30 min腹腔注射地西泮5 mg／kg;N-SR组:假照射前未用药。D-R、N-R组建立清醒状态下大鼠放射性脑损伤模型。分别于照射前即刻、照射后6 h、1 d、1周和1月时记录磁共振成像(MRI)T1加权、T2加权的信号强度及其增强率,测定脑组织中伊文思蓝(EB)含量,免疫组化法分析海马神经元血管内皮生长因子(VEGF)的表达,并观察病理形态学的改变。结果 N-R组照射后T1加权的信号强度降低,T2加权的信号强度和信号强度的增强率升高,D-R组上述MRI的改变均比N-R组降低,D-R组脑组织EB含量在照射后6 h、1周和1月时及照射后6 h VEGF表达较N-R组降低(P<0．05或0．01)。结论在照射前使用地西泮通过降低脑组织VEGF表达,降低了放射性脑损伤大鼠血脑屏障的通透性,对放射性脑损伤有一定的防护作用。     

Severity profile of penetrating ballistic-like brain injury on neurofunctional outcome, blood-brain barrier permeability, and brain edema formation

This study evaluated the injury severity profile of unilateral, frontal penetrating ballistic-like brain injury (PBBI) on neurofunctional outcome, blood-brain barrier (BBB) permeability, and brain edema formation. The degree of injury severity was determined by the delivery of a water-pressure pulse designed to produce a temporary cavity by rapid (<40?ms) expansion of the probe's elastic balloon calibrated to equal 5%, 10%, 12.5%, or 15% of total rat brain volume (control groups consisted of sham surgery or insertion of the probe only). Neurofunctional assessments revealed motor and cognitive deficits related to the degree of injury severity, with the most clear-cut profile of PBBI injury severity depicted by the Morris water maze (MWM) results. A biphasic pattern of BBB leakage was detected in the injured hemisphere at all injury severity levels at 4?h post-injury, and again at 48-72?h post-injury, which remained evident out to 7 days post-PBBI in the 10% and 12.5% PBBI groups. Likewise, significant brain edema was detected in the injured hemisphere by 4?h post-injury and remained elevated out to 7 days post-injury in the 10% and 12.5% PBBI groups. However, following 5% PBBI, significant levels of edema were only detected from 24?h to 48h post-injury. These results identify an injury severity profile of BBB permeability, brain edema, and neurofunctional impairment that provides sensitive and clinically relevant outcome metrics for studying potential therapeutics.     

Neuroprotective effects of mildronate in a rat model of traumatic brain injury

ObjectiveTraumatic brain injury (TBI) is one of the most common preventable causes of mortality and morbidity. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophysiological mechanisms underlying neuronal loss after TBI. Mildronate is demonstrated to be beneficial in various experimental models of ischemic diseases via anti-inflammatory, antioxidant, and neuroprotective mechanisms. This study aimed to investigate possible antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of mildronate in a rat model of TBI.MethodsA total of 46 male rats were divided into three groups of control, saline-treated TBI, and mildronate-treated TBI. Both TBI groups were subjected to closed-head contusive weight-drop injuries followed by treatment with saline or mildronate (100 mg/kg) administered intraperitoneally. The forebrain was removed 24 h after trauma induction, the activities of myeloperoxidase (MPO) and caspase-3, levels of superoxide dismutase (SOD), luminol- and lucigenin-enhanced chemiluminescence were measured, and histomorphological evaluation of cerebral tissues was performed.ResultsIncreased MPO and caspase-3 activities in the vehicle-treated TBI group (p < 0.001) were suppressed in the mildronate-treated TBI group (p < 0.001). Similarly, increase in luminol and lucigenin levels (p < 0.001 and p < 0.01, respectively) in the vehicle-treated TBI group were decreased in the mildronate-treated TBI group (p < 0.001). Concomitantly, in the vehicle-treated TBI group, TBI-induced decrease in SOD activity (p < 0.01) was reversed with mildronate treatment (p < 0.05). On histopathological examination, TBI-induced damage in the cerebral cortex was lesser in the mildronate-treated TBI group than that in other groups.ConclusionThis study revealed for the first time that mildronate, exhibits neuroprotective effects against TBI because of its anti-inflammatory, antiapoptotic, and antioxidant activities.     

Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal blood-brain barrier function after traumatic brain injury

Serum S100B elevations accurately reflect blood-brain barrier (BBB) damage. Because S100B is also present in peripheral tissues, release of this protein may not be specific to central nervous system (CNS) injury. Ubiquitin C-terminal hydrolase 1 (UCHL1), and phosphorylated neurofilament heavy chain (pNF-H) are found exclusively in neurons, but their relationship to BBB dysfunction has not been determined. The objective of this study was to determine the accuracy of serum UCHL1 and pNF-H as measures of BBB integrity after traumatic brain injury (TBI), to and compare them to S100B. We performed a prospective study of 16 patients with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤12) and 6 patients with non-traumatic headache who had cerebrospinal fluid (CSF) collected by ventriculostomy or lumbar puncture (LP). Serum and CSF were collected at the time of LP for headache patients and at 12, 24, and 48?h after injury for TBI patients. BBB function was determined by calculating albumin quotients (Q(A)), where Q(A)=[albumin(CSF)]/[albumin(serum)]. S100B, UCHL1, and pNF-H were measured by enzyme-linked immunosorbent assay (ELISA). Pearson's correlation coefficient and area under the receiver operator characteristic (ROC) curve were used to determine relationships between serum markers and Q(A). At 12 hours after TBI, a significant relationship was found between Q(A) and serum UCHL1 concentrations (AUC=0.76; 95% CI 0.55,1.00), and between Q(A) and serum S100B concentrations (AUC=0.794; 95% CI 0.57,1.02). There was no significant relationship found between these markers and Q(A) at other time points, or between pNF-H and Q(A) at any time point. We conclude that serum concentrations of UCHL1 are associated with abnormal BBB status 12?h after moderate to severe TBI. This relationship is similar to that observed between serum S100B and Q(A,) despite the fact that S100B may be released from peripheral tissues after multi-trauma. We conclude that peripheral release of S100B after multi-trauma is probably negligible and that UCHL1 may have some utility to monitor BBB disruption 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.     

Detection of alphaII-spectrin and breakdown products in humans after severe traumatic brain injury

AIM: alphaII-Spectrin is the major structural component of the cortical membrane cytoskeleton. It is a major substrate for the calpain and caspase-3 cysteine proteases there are considerable evidence that alfaII-spectrin is processed by the calpains and caspase-3 to signature cleavage products in vivo after experimental traumatic brain injury (TBI). We sought to determine whether aII-spectrin proteolysis is a potentially reliable biomarker for TBI in humans measuring the levels of spectrin and spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI, and studying the relationship between these levels and clinical outcome. METHODS: This prospective case control study enrolled 8 patients with severe TBI, defined by a Glasgow Coma Score (GCS) of <8, and requiring intraventricular pressure monitoring. Patients without TBI requiring CSF drainage served as controls. Ventricular CSF was drained from each patient at 6, 12, 24, 48, 72, and 96 h following TBI and measured for spectrin and SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. RESULTS: CSF alphaII-spectrin and calpain and caspase-3 mediated SBDP levels were significantly increased compared to control patients at all time points examined (P<0.001). In patients with a better outcome, CSF spectrin and SBDPs significantly decreased from 6 to 96 h. Patients whose spectrin and SBDP levels remained elevated or failed to decline had a worse outcome (P<0.019). CONCLUSIONS: The present work provides the first evidence that protein degradation of alphaII-spectrin is a reliable marker of severe TBI in humans and that both necrotic and apoptotic cell death mechanisms are activated in humans following a severe TBI. Moreover, the temporal profile of degradation may be an important indicator of clinical outcome.     

Cellular inflammatory response associated with breakdown of the blood-brain barrier after closed head injury in rats

This study reports a widespread microglial response characterized by an upregulation of surface antigens, such as complement type 3 receptors (CR3) and major histocompatibility complex (MHC) class II antigens on these cells following closed head injury. Increased expression of CR3 (OX-42) and MHC class II antigens (OX-6) was observed in rats killed at 1, 3, and 5 days after injury. Intense OX-42 immunoreactivity was observed in microglial cells throughout the brain with a smaller number of them being OX-6 positive. In addition to microglial reaction, astrocytic activation reflected in cellular hypertrophy and increased immunoreactivity for glial fibrillary acidic protein (GFAP) was observed at 5 days after head injury. Together with the above, a diffuse perivascular and intraneuronal immunostaining for immunoglobulin G (IgG) was observed primarily in the cerebral cortex. This was accompanied by an enhanced expression of both endothelial nitric oxide synthase (eNOS) in blood vessels and inducible nitric oxide synthase (iNOS) in brain macrophages. In rats subjected to closed head injury followed by a single intraperitoneal (i.p.) injection of rhodamine isothiocyanate (RhIc), seepage of the fluorescent dye into the neuropil was observed. This had resulted in the labelling of the cortical neurons clearly demonstrating a breakdown of the blood-brain barrier (BBB). In the latter, it is conceivable that the ensuing leakage of plasma immunoglobulins and other serum-derived materials could induce the expression of MHC class II antigens on microglia. The mechanism causing the BBB dysfunction is not clear, although present results suggest that excessive release of nitric oxide (NO) may be a contributory factor. The widespread activation of microglia in rats after head injury suggests their involvement in increased endocytosis and immunological responses.     

Neuroprotective anti-apoptosis effect of estrogens in traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of death and functional disability in western countries, affecting mostly young patients. Despite intense and sustained efforts deployed for the development of new therapeutic strategies, no clinical benefit has been shown by any of the investigated compounds. Increasing attention has been drawn during the past two decades to the neuroprotective effects of estrogens, although most of the available data relate to ischemic brain injury. The purpose of the present study was to investigate the potential neuroprotective value of estrogens in TBI as a therapeutic modality. For this purpose, a contusion was created in the parietal cortex by dynamic cortical deformation in two groups of 10 Sprague-Dawley male rats. Following the injury, treated animals received conjugated estrogens for 3 days, using a subcutaneously implanted osmotic pump. Animals were then sacrificed, and TUNEL, anti-active Caspase 3, bcl-2, and bax labeling were performed in paraffin-embedded brain sections, allowing for comparative and quantitative analysis. In estrogen-treated animals, there was a marked and significant reduction of apoptosis in comparison with non-treated animals. The reduction in TUNEL and active Caspase 3 staining was similar and close to 50%. Optical analysis of histological slides prepared by bcl-2 labeling showed a significant increase in bcl-2 expression in estrogen-treated animals compared to non-treated animals. On the contrary, bax expression was not influenced by hormonal treatment, and no difference could be noticed between the two groups. These results support the potential therapeutic value of estrogens in TBI and further clarify their mode of action.     

酮体代谢在颅脑创伤中对脑组织的神经保护作用

【摘要】〓外伤性脑损伤后造成脑组织缺血缺氧,继发炎症、脑血肿、脑肿胀、脑水肿、颇内压升高等一系列病理生理学变化。在颅脑创伤中,继发性颅脑损伤是引起急性病情恶化和招致病人死亡、致残的主要原因。颅脑创伤后会出现葡萄糖代谢障碍,从而影响神经元的代谢和能量来源。生酮饮食是一种高脂肪、低碳水化合物、低蛋白的饮食治疗方案,机体主要依靠脂肪而不是碳水化合物来供应能量,已用于临床抗癫痫的治疗,其有效性和安全性已得到国际公认。近来有报道证实颅脑创伤后生酮饮食可以延缓细胞调亡,起到神经保护作用,并能减轻脑水肿。现就酮体代谢对颅脑创伤后的神经保护作用进行综述。     

Neuroprotective effects of selective group II mGluR activation in brain trauma and traumatic neuronal injury

The effects of group II mGluR activation by selective agonist (-)-2-oxa-4-aminobicyclo[3.1. 0]hexane-4,6-dicarboxylate (LY379268) were examined in a mouse model of controlled cortical impact (CCI)-induced brain injury and in primary neuronal/glial and neuronal cultures subjected to mechanical trauma. Systemic administration of LY379268 to mice at 30 min after CCI significantly improved both motor and cognitive recovery as compared with vehicle-treated control animals. LY379268 also significantly reduced cell death induced by mechanical injury in rat neuronal/glial and neuronal cultures, as measured by lactate dehydrogenase (LDH) release assay. The neuroprotective effect of LY379268 in vitro was abolished by co-administration of the mGluR2/3 antagonist (s)-alpha-ethylglutamic acid (EGLU); however, co-application of selective mGluR3 antagonist beta-N-acetyl-aspartyl-glutamate (NAAG) had no significant influence in the same system. Together, these findings demonstrate the neuroprotective activity of group II mGluR activation and underscore the role of the mGluR2 subtype for this effect.     

颅脑外伤后进展性脑损害的研究进展

颅脑外伤后进展性脑损害,包括脑出血、脑缺血、脑水肿,都是影响颅脑外伤预后的重要因素.本文复习文献,对颅脑外伤后进展性脑损害的发病率、发生机制、早期诊断方法、治疗和预后等相关问题的研究进展进行了综述.     

Neuroprotective effects of the Ras inhibitor S-trans-trans-farnesylthiosalicylic acid, measured by diffusion-weighted imaging after traumatic brain injury in rats

Ras proteins play a role in receptor-mediated signaling pathways and are activated after traumatic brain injury. S-trans-trans-farnesylthiosalicylic acid (FTS), a synthetic Ras inhibitor, acts primarily on the active, GTP-bound form of Ras and was shown to improve neurobehavioral outcome after closed head injury (CHI) in mice. To gain a better understanding of the neuroprotective mechanism of FTS, we used diffusion-weighted imaging (DWI) in a rat model of CHI. Apparent diffusion coefficients (ADC) and transverse relaxation times (T2) were measured in injured rat brains after treatment with vehicle or FTS (5 mg/kg). Neuroprotection by FTS was also assessed in terms of the neurological severity score. One week after injury, significantly better recovery was observed in the FTS-treated rats than in the controls (p = 0.0191). T2 analysis of the magnetic resonance images revealed no differences between the two groups. In contrast, they differed significantly in ADC, particularly at 24 h post-CHI (p < 0.05): in the vehicle-treated rats ADC had decreased to approximately 26% below baseline, whereas it had increased to about 10% above baseline in the FTS-treated rats. As the magnitude of ADC reduction is strongly linked to blood perfusion deficit, these results suggest that the neuroprotective mechanism of FTS might be related to an improvement in cerebral perfusion. We propose that FTS, which is currently being tested in humans for anti-cancer indications, should also be considered as a new strategy for the management of head injury.