12-O-Tetradecanoylphorbol 13-Acetate and Fibroblast Growth Factor Increase the 30-kDa Substrate Binding Subunit of Type II Deiodinase in Astrocytes

Abstract: Type II 5′-deiodinase (D-II) catalyzes the intracellular conversion of thyroxine (T₄) to 3,5,3′-triiodothyronine (T₃) in the brain., The D-II activity in astroglial cell cultures is induced by several pathways including cyclic AMP (cAMP), 12-O-tetradecanoylphorbol 13-acetate (TPA), and fibroblast growth factors (FGFs). We have examined the effect of TPA and FGFs on the 30-kDa substrate binding subunit of D-II, by affinity labeling with N-bromoacetyl-[¹²⁸I]T₄ in astroglial cells. TPA (0.1 μM), 20 ng/ml acidic FGF (aFGF), and 1 mM 8-bromo cyclic AMP all caused an increase in the 30-kDa protein. cAMP induced the greatest increase (fivefold) followed by TPA (3.2-fold) and FGF (2.8-fold). Glucocorticoids acted synergistically with cAMP and aFGF and promoted the effect of TPA. Affinity labeling was competitively inhibited by bromoacetyl-T₄ > bromoacetyl-T₃ > T₄ > reverse T₃ > iopanoic acid > T₃ > 3,5,3-triiodothyroacetic acid. The effect of TPA (0.1 μM) was maximum at 8 h and then gradually decreased. aFGF (20 ng/ml) plus heparin (17 μg/ml) induced a maximal 30-kDa increase at 8 h, which stayed stable for up to 24 h. The effect of aFGF was concentration dependent. Of the other growth factors studied, only basic FGF and platelet-derived growth factor induced small increases in the 30-kDa protein. Epidermal growth factor had little effect. In vitro labeling of cAMP, TPA, and aFGF-stimulated cell sonicates resulted in an increase in the 30-kDa protein that paralleled the increase in D-II activity. These results correlate well with our previous studies showing that several distinct signaling pathways regulate D-II activity. They suggest that the regulation of D-II in astrocytes by cAMP, TPA, and aFGF involves an accumulation of the 30-kDa substrate binding subunit.     

Delayed Phospholipid Degradation in Rat Brain After Traumatic Brain Injury

Abstract: Lipid second messengers such as arachidonic acid and its metabolites and diacylglycerols (DAGs) are affected in brain injury. Therefore, changes in the pool size and the fatty acid composition of free fatty acids (FFAs) and DAGs were analyzed in different rat brain areas 4 and 35 days after traumatic injury. Cortical impact injury of low-grade severity was applied in the right frontal somatosensory cortex. Four days after injury, FFAs and DAGs were increased by three- and twofold, respectively, in the injured cortex and to a lesser extent in the contralateral cortex compared with sham-operated animals. Docosahexaenoic acid followed by stearic acid, and arachidonic acid, displayed the greatest changes in both FFAs and DAGs. By day 35, free stearic, oleic, and arachidonic acids remained elevated in the damaged cortex (1.5-fold each). DAGs showed the greatest change, reaching values 2.7-fold higher than sham in all frontal and occipital cortical areas, including brainstem. Oleoyl- and arachidonoyl-DAGs (four- and threefold increase, respectively) followed by docosahexaenoyl-DAGs (twofold) contributed to the DAG accumulation. These results reveal that traumatic brain injury triggers a sustained and time-dependent activation of phospholipase-mediated signaling pathways leading to membrane phospholipid degradation and targeting, early on, docosahexaenoyl phospholipid-enriched excitable membranes.     

SPARC/Osteonectin mRNA Is Induced in Blood Vessels Following Injury to the Adult Rat Cerebral Cortex

Recently we described the pattern of expression of the anti-adhesive glycoprotein SPARC/osteonectin in the developing and adult brain. SPARC mRNA was present in developing blood vessels during neurogenesis, but was not detected in the mature vasculature. We have now examined the effect of a lesion to the adult rat cerebral cortex on the expression of SPARC by in situ hybridization. SPARC mRNA was increased in the zone proximal to the wound at 3 to 10 days after cortical brain injury. During this period, SPARC was induced in mature blood vessels close to the lesion site and in blood vessels which develop following injury. These results suggest a role for SPARC in the process of angiogenesis following injury to the adult cerebral cortex.     

Increased Expression of Apolipoprotein D Following Experimental Traumatic Brain Injury

Increasing evidence suggests that apolipoprotein D (apoD) could play a major role in mediating neuronal degeneration and regeneration in the CNS and the PNS. To investigate further the temporal pattern of apoD expression after experimental traumatic brain injury in the rat, male Sprague-Dawley rats were subjected to unilateral cortical impact injury. The animals were killed and examined for apoD mRNA and protein expression and for immunohistological analysis at intervals from 15 min to 14 days after injury. Increased apoD mRNA and protein levels were seen in the cortex and hippocampus ipsilateral to the injury site from 48 h to 14 days after the trauma. Immunohistological investigation demonstrated a differential pattern of apoD expression in the cortex and hippocampus, respectively: Increased apoD immunoreactivity in glial cells was detected from 2 to 3 days after the injury in cortex and hippocampus. In contrast, increased expression of apoD was seen in cortical and hippocampal neurons at later time points following impact injury. Concurrent histopathological examination using hematoxylin and eosin demonstrated dark, shrunken neurons in the cortex ipsilateral to the injury site. In contrast, no evidence of cell death was observed in the hippocampus ipsilateral to the injury site up to 14 days after the trauma. No evidence of increased apoD mRNA or protein expression or neuronal pathology by hematoxylin and eosin staining was detected in the contralateral cortex and hippocampus. Our results reveal induction of apoD expression in the cortex and hippocampus following traumatic brain injury in the rat. Our data also suggest that increased apoD expression may play an important role in cortical neuronal degeneration after brain injury in vivo. However, increased expression of apoD in the hippocampus may not necessarily be indicative of neuronal death.     

Effects of Organotins on Rat Brain Astrocytes in Culture

Abstract: The interaction of triethyltin (TET) and trimethyltin (TMT) with rat brain astrocytes in vitro was investigated. Both compounds are highly neurotoxic after in vivo application, cause neurobehavioral changes, and elicit neuronal and glial responses in the CNS. In this study, 5-week-old cultures were exposed to TMT or TET (0.1–2.5 µM) for 24 h. A concentration-dependent cytotoxicity was observed for both agents by vital dye uptake assay using neutral red (NR). The order of potency for half-maximal cytotoxicity (NR-50) was TET (0.7 µM)> TMT (2.5 µM), in agreement with results found after in vivo administration. TET and TMT caused similar morphological changes: large holes extending through the plasma membrane appeared initially in the flattened cell bodies, cytoplasmic extensions were retracted, and long cellular processes formed. Later, the cell bodies rounded up and had only a few extremely long and thin processes. Indirect immunofluorescence staining using anti-vimentin and anti-glial fibrillary acidic protein (GFAP) antibodies revealed that the orderly array of the intermediate filament system was severely disturbed. At lower concentrations, an increased bundling was observed, and at higher concentrations the disassembly of the intracellular framework was seen, and cellular staining appeared rather diffuse. Western blot analysis of cellular extracts was carried out to determine the protein levels of GFAP and vimentin. In this culture system, TET and TMT caused an almost two-fold increase in the levels of GFAP at concentrations around and below NR-50, indicating that astrocytes react to organotics independently of neuronal signals. Concomitantly, TET (0.7 µM) and TMT (2.5 µM) led to a 63% decrease in the activity of ecto-5′-nucleotidase, which in addition to its enzymatic function, represents a transmembrane cell surface protein and has been implicated in cellular adhesion and cell communication processes. Thus, triorganotins directly affect astrocytes in culture and alter their functional stage even in the absence of neurons.     

Traumatic Brain Injury Down-Regulates Glial Glutamate Transporter (GLT-1 and GLAST) Proteins in Rat Brain

Abstract: Excess activation of NMDA receptors is felt to participate in secondary neuronal damage after traumatic brain injury (TBI). Increased extracellular glutamate is active in this process and may result from either increased release or decreased reuptake. The two high-affinity sodium-dependent glial transporters [glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST)] mediate the bulk of glutamate transport. We studied the protein levels of GLT-1 and GLAST in the brains of rats after controlled cortical impact-induced TBI. With use of subtype-specific antibodies, GLT-1 and GLAST proteins were quantitated by immunoblotting in the ipsilateral and contralateral cortex at 2, 6, 24, 72, and 168 h after the injury. Sham-operated rats served as control. TBI resulted in a significant decrease in GLT-1 (by 20–45%; p < 0.05) and GLAST (by 30–50%; p < 0.05) protein levels between 6 and 72 h after the injury. d -[³H]Aspartate binding also decreased significantly (by 30–50%; p < 0.05) between 6 and 72 h after the injury. Decreased glial glutamate transporter function may contribute to the increased extracellular glutamate that may mediate the excitotoxic neuronal damage after TBI. This is a first report showing altered levels of glutamate transporter proteins after TBI.     

Energy Metabolic Changes in the Early Post-injury Period Following Traumatic Brain Injury in Rats

Impaired cerebral energy metabolism may be a major contributor to the secondary injury cascade that occurs following traumatic brain injury (TBI). To estimate the cortical energy metabolic state following mild and severe controlled cortical contusion (CCC) TBI in rats, ipsi-and contralateral cortical tissues were frozen in situ at 15 and 40 min post-injury and adenylate (ATP, ADP, AMP) levels were analyzed using high-performance liquid chromatography (HPLC) and the energy charge (EC) was calculated. At 15 min post-injury, mildly brain-injured animals showed a 43% decrease in cortical ATP levels and a 2.4-fold increase in AMP levels (P < 0.05), and there was a significant reduction of the ipsilateral cortical EC when compared to sham-injured animals (P < 0.05). At 40 min post-injury, the ipsilateral adenylate levels and EC had recovered to the values observed in the sham-injury group. In the severe CCC group, there was a 51% decrease in ipsilateral cortical ATP levels and a 5.3-fold increase in AMP levels with a significant reduction of cortical EC at 15 min post-injury (P < 0.05). At 40 min post-injury, a 2.6-fold ipsilateral increase in AMP levels and an 11% and 44% decrease in EC and ATP levels, respectively, remained (P < 0.05). A 37–38% reduction of the total adenylate pool was observed ipsilaterally in both CCC severity groups at the early time-point, and a 19% and 28% decrease remained in the mild and severe CCC groups, respectively, at 40 min post-injury. Significant contralateral ATP and EC changes were only observed in the severe CCC group at 40 min post-injury (P < 0.05). The energy-requiring secondary injury cascades that occur early post-injury do not challenge the brain tissue to the extent of ATP depletion and may provide a window of opportunity for therapeutic intervention.     

Changes in Metabotropic Glutamate Receptor mRNA Levels Following Global Ischemia: Increase of a Putative Presynaptic Subtype (mGluR4) in Highly Vulnerable Rat Brain Areas

Abstract: Metabotropic glutamate receptors mediate their intracellular response by coupling to G proteins and may be divided into three subfamilies: mGluR1 and mGluR5, which stimulate phosphatidylinositol hydrolysis; mGluR2 and mGluR3, which are negatively coupled to cyclic AMP formation; and mGluR4 and mGluR6, which also inhibit forskolin-stimulated cyclic AMP formation. The mGluR4 subtypes may represent l -2-amino-4-phosphonobutyrate-sensitive presynaptic autoreceptors, and two alternatively spliced variants of the mGluR4 coding for two receptors with different C termini have been identified. Using in situ hybridization, we measured the levels of mGluR1–mGluR5 mRNA in regions of the rat brain 24 h after transient global ischemia, a time point when no neuronal damage can yet be observed morphologically. In the hippocampus, the mRNA levels for mGluR1, mGluR2, and mGluR5 were decreased, mGluR3 mRNA levels were unchanged, and the mGluR4 mRNA levels were strongly increased. The strongest increase appeared to be in the mRNA encoding mGluR4b. The mGluR4 mRNA was also increased in the parietal cortex, whereas the ventral posteromedial thalamic nucleus showed a small decrease in its mRNA content. These results suggest that vulnerable neurons react to an increased extracellular glutamate concentration by differential regulation of the mRNA for pre- and postsynaptically located metabotropic glutamate receptors.     

重度创伤性脑损伤后肠黏膜屏障应激性变化的模型

目的建立一种观察重度创伤性脑损伤(TBI)后肠黏膜屏障(IMB)应激性变化的模型。方法选用雄性Wistar大鼠64只,随机分为两组。TBI组(32只):采用改良的Feeney自由落体撞击法,建立TBI模型;假手术对照组(32只):只开骨窗,不行落体致伤。两组大鼠分别按术后6、12、24和48h时相点分为4个亚组(每组均为8只),观察脑组织、肠黏膜组织病理以及扫描和透射电镜下肠黏膜超微结构的变化。结果光镜下TBI组肠黏膜上皮细胞受损,电镜下还可见细胞间紧密连接较对照组明显增宽。结论用改良的Feeney自由落体撞击法,建立的重度TBI大鼠模型肠黏膜上皮细胞受损,细胞间紧密连接增宽,提示其IMB的功能的确发生了应激性损害,说明这种用来观察重度TBI后IMB应激性变化的模型是成功的。     

Acute and Persistent Suppression of Preproenkephalin mRNA Expression in the Striatum Following Developmental Hypoxic-Ischemic Injury

Abstract: The striatum is vulnerable to hypoxic-ischemic injury during development. In a rodent model of perinatal hypoxia-ischemia, it has been shown that striatal neurons are not uniformly vulnerable. Cholinergic neurons and NADPH-diaphorase-positive neurons are relatively spared. However, it is unknown what classes of striatal neurons are relatively sensitive. One of the major classes of striatal neurons uses enkephalin as a neurotransmitter. We have studied the effect of early hypoxic-ischemic injury on this class of neurons using a quantitative solution hybridization assay for preproenkephalin mRNA in conjunction with in situ hybridization. Hypoxia-ischemia results in an early (up to 24 h) decrease in striatal preproenkephalin mRNA, which is shown by in situ hybridization to occur mainly in the dorsal portion of the striatum. By 14 days, whole striatal preproenkephalin mRNA and total enkephalin-containing peptide levels are normal. However, at 14 days, in situ hybridization reveals that regions of complete preproenkephalin mRNA-positive neuron loss remain in the dorsal region. Normal whole striatal levels are due to an up-regulation of preproenkephalin mRNA expression in the ventrolateral region of the injured striatum. Given the important role that the enkephalin-containing striatal efferent projection plays in regulating motor function, its relative loss may be important in the chronic disturbances of motor control observed in brain injury due to developmental hypoxic-ischemic injury.     

丙泊酚镇静对颅脑损伤患者脑氧供需平衡的影响

目的:探讨丙泊酚实施不同程度镇静对颅脑损伤患者脑氧供需平衡的影响。方法:选择急性闭合性颅脑损伤需行机械通气患者46例,随机分为轻度镇静组(A组),设定目标脑电双频谱指数(BIS)值75%;中度镇静组(B组),设定目标BIS值65%。主要观察达设定目标BIS值时丙泊酚靶控输注(TCI)浓度、Ramsay镇静评分、脑氧供需平衡指标颈内静脉血氧饱和度(SjvO_2)和脑氧摄取率(CERO_2)以及心率(HR)、平均动脉压(MAP)。结果:两组设定镇静目标需丙泊酚TCI浓度有明显差异(P0.05),但Ramsay评分比较差异无统计学意义;中度镇静组SjvO_2较基础值增加约12%(P0.05),CERO_2较基础值下降约15%(P0.05);而轻度镇静组对SjvO_2和CERO_2基础值没有影响。两组HR均较基础值减慢(P0.05),但对MAP均没有影响。结论:颅脑损伤患者维持目标镇静BIS值65%,调控丙泊酚靶浓度1.5-1.6μg/mL,更有利于改善脑氧供需平衡。     

急诊绿色通道提高颅脑外伤患者救治效果的体会

目的:评价建立急诊绿色通道对救治颅脑外伤患者的价值.方法:采用回顾性分析方法,收集我院2007年1月～2012年1月救治的颅脑外伤患者199例,其中急诊绿色通道组111例(A组)和非急诊绿色通道组88例(B组)的救治情况进行比较,分析两组救治的疗效、死亡率及预后.结果:199例颅脑外伤患者中,绿色通道组(A组)111例(55.78％),死亡26例(23.42％),对照组88例(44.22％),死亡30例(34.09％).A组的有效治疗时间较B组明显缩短,差异有统计学意义(0.01＜P＜0.05);A组硬膜外血肿(33例)的术前血肿量少于B组(30例),预后较B组好,差异有统计学意义(0.01＜P＜0.05);A组的中重型颅脑外伤的死亡率明显低于B组,差异有统计学意义(0.01＜P＜0.05),两组特重性颅脑外伤的死亡率仍较高,差异无统计学意义(P＞0.05).结论:急诊绿色通道可缩短颅脑外伤患者救治等待时间,改善中重型颅脑外伤患者的预后.     

大鼠脑创伤后caspase-3的过度表达与细胞凋亡的关系

目的：探讨大鼠脑创伤后海马神经组织中casepase-3表达及其在细胞凋亡中的机制。方法：雄性Wistar大鼠72只随机分成对照组和创伤组。用Marmarou方法造成大鼠重型弥漫性颅脑创伤,采用免疫组织化学检测海马CA1区神经细胞casepase-3蛋白表达情况,原位细胞DNA断裂检测末端标记（TUNEL）法观察大鼠海马CA1区神经细胞凋亡动态变化。同时行TUNEL与caspase-3双标染色。结果：对照组海马区神经细胞casepase-3未见明显表达,创伤组海马CA1区神经细胞casepase-3表达在伤后3小时开始升高,伤后3天达高峰（P〈0．01）,伤后7天下降明显。对照组海马区未见TUNEL阳性细胞,创伤组海马区TUNEL阳性细胞伤后3小时开始增多,伤后3天达高峰（P〈0．01）,伤后7天下降。可见创伤组TUNEL染色与caspase-3免疫染色双标阳性的细胞伤后6小时细胞数量逐渐增多,于伤后3天达高峰（P〈0．01）,伤后7天双标阳性细胞数量下降。Casepase-3表达与TUNEL阳性细胞明显相关（P〈0．01）。结论：大鼠脑创伤后casepase-3的过度表达是影响大鼠脑创伤后神经细胞凋亡原因之一,抑制casepase-3活性表达对神经组织起保护作用。     

Quantification of Axonal Damage in Traumatic Brain Injury

Abstract : Diffuse axonal injury is a primary feature of head trauma and is one of the most frequent causes of mortality and morbidity. Diffuse axonal injury is microscopic in nature and difficult or impossible to detect with imaging techniques. The objective of the present study was to determine whether axonal injury in head trauma patients could be quantified by measuring levels of CSF tau proteins. Tau proteins are structural microtubule binding proteins primarily localized in the axonal compartment of neurons. Monoclonal antibodies recognizing the form of tau found in the CSF of head trauma patients were developed by differential CSF hybridoma screening using CSF from head trauma and control patients. Clones positive for head trauma CSF tau proteins were used to characterize this form of tau and for ELISA development. Using the developed ELISA, CSF tau levels were elevated >1,000-fold in head trauma patients (mean, 1,519 ng/ml of CSF) when compared with patients with multiple sclerosis (mean, 0.014 ng/ml of CSF ; p < 0.001), normal pressure hydrocephalus (nondetectable CSF tau), neurologic controls (mean, 0.031 ng/ml of CSF ; p < 0.001), or nonneurologic controls (nondetectable CSF tau ; p < 0.001). In head trauma, a relationship between clinical improvement and decreased CSF tau levels was observed. These data suggest that CSF tau levels may prove a clinically useful assay for quantifying the axonal injury associated with head trauma and monitoring efficacy of neuroprotective agents. Affinity purification of CSF tau from head trauma patients indicated a uniform cleavage of ~ 18 kDa from all six tau isoforms, reducing their apparent molecular sizes to 30-50 kDa. These cleaved forms of CSF tau consisted of the interior portion of the tau sequence, including the microtubule binding domain, as judged by cyanogen bromide digestion. Consistent with these data, CSF cleaved tau bound taxolpolymerized microtubules, indicating a functionally intact microtubule binding domain. Furthermore, epitope mapping studies suggested that CSF cleaved tau proteins consist of the interior portion of the tau sequence with cleavage at both N and C terminals.     

大鼠脑创伤后caspase-3的过度表达与细胞凋亡的关系

目的:探讨大鼠脑创伤后海马神经组织中casepase-3表达及其在细胞凋亡中的机制。方法:雄性Wistar大鼠72只随机分成对照组和创伤组,用Marmarou方法造成大鼠重型弥漫性颅脑创伤,采用免疫组织化学检测海马CA1区神经细胞casepase-3蛋白表达情况,原位细胞DNA断裂检测末端标记(TUNEL)法观察大鼠海马CA1区神经细胞凋亡动态变化。同时行TUNEL与caspase-3双标染色。结果:对照组海马区神经细胞casepase-3未见明显表达,创伤组海马CA1区神经细胞casepase-3表达在伤后3小时开始升高,伤后3天达高峰(P0.01),伤后7天下降明显。对照组海马区未见TUNEL阳性细胞,创伤组海马区TUNEL阳性细胞伤后3小时开始增多,伤后3天达高峰(P0.01),伤后7天下降。可见创伤组TUNEL染色与caspase-3免疫染色双标阳性的细胞伤后6小时细胞数量逐渐增多,于伤后3天达高峰(P0.01),伤后7天双标阳性细胞数量下降。Casepase-3表达与TUNEL阳性细胞明显相关(P0.01)。结论:大鼠脑创伤后casepase-3的过度表达是影响大鼠脑创伤后神经细胞凋亡原因之一,抑制casepase-3活性表达对神经组织起保护作用。     

神经干细胞移植对脑损伤大鼠整合素表达的影响

目的探讨神经干细胞（NSCs）移植对大鼠创伤性脑损伤（TBI）整合素（integrin）表达的影响。方法从E14大鼠胚胎分离NSCs,进行原代培养及传代培养;对NSCs进行诱导分化;采用免疫细胞化学技术对NSCs和其分化为神经元的表型进行鉴定。采用改良的Feeney法制备创伤性脑损伤模型。利用脑立体定位仪和微量注射泵进行NSCs脑内移植。采用免疫组织化学技术、免疫印迹技术和RT—PCR技术检测在移植后不同时间脑组织损伤区整合素的表达。结果在培养基中,NSCs呈球团状悬浮生长,Nestin表达阳性。用含10％胎牛血清的培养基对NSCs进行体外诱导分化后第2d,多数细胞伸出突起,以后突起逐渐延长,分支增加。分化后第5d,部分细胞呈βⅢ-微管蛋白阳性。整合素阳性产物主要表达于细胞膜,呈棕黄色。在对照组及移植组均可见阳性细胞表达。在不同时间点,NSCs移植组移植点及其周围脑组织中整合素的mRNA表达均显著高于对照组（P〈O．01）。整合素的蛋白表达结果和tuRNA表达结果相一致。结论移植NSCs至TBI大鼠损伤脑组织,在移植点周围脑组织中整合素的表达显著增加。     

Temporal Patterns of Poly(ADP-Ribose) Polymerase Activation in the Cortex Following Experimental Brain Injury in the Rat

The activation of poly(ADP-ribose) polymerase, a DNA base excision repair enzyme, is indicative of DNA damage. This enzyme also undergoes site-specific proteolysis during apoptosis. Because both DNA fragmentation and apoptosis are known to occur following experimental brain injury, we investigated the effect of lateral fluid percussion brain injury on poly(ADP-ribose) polymerase activity and cleavage. Male Sprague-Dawley rats (n = 52) were anesthetized, subjected to fluid percussion brain injury of moderate severity (2.5-2.8 atm), and killed at 30 min, 2 h, 6 h, 24 h, 3 days, or 7 days postinjury. Genomic DNA from injured cortex at 24 h, but not at 30 min, was both fragmented and able to stimulate exogenous poly(ADP-ribose) polymerase. Endogenous poly(ADP-ribose) polymerase activity, however, was enhanced in the injured cortex at 30 min but subsequently returned to baseline levels. Slight fragmentation of poly(ADP-ribose) polymerase was detected in the injured cortex in the first 3 days following injury, but significant cleavage was detected at 7 days postinjury. Taken together, these data suggest that poly(ADP-ribose) polymerase-mediated DNA repair is initiated in the acute posttraumatic period but that subsequent poly(ADP-ribose) polymerase activation does not occur, possibly owing to delayed apoptosis-associated proteolysis, which may impair the repair of damaged DNA.     

急性酒精中毒合并中度创伤性脑损伤大鼠海马AQP4的表达

目的:探讨大鼠急性酒精中毒合并颅脑外伤后AQP4在海马区表达的变化.方法:健康成年雄性SD大鼠96只,随机分为4组:假手术组(N组)、急性酒精中毒组(A组)、中度创伤性脑损伤组(T组)和急性酒精中毒合并中度创伤性脑损伤(AT组).腹腔注射酒精(2.5g/kg),2h后以重物自由落体击打大鼠头部建立急性酒精中毒合并中度创伤性脑损伤(traumatic brain injury,TBI)动物模型.各组动物分别存活1、3、5、14天.免疫组化方法检测海马CA1区AQP4的表达.结果:AQP4阳性产物分布于胶质纤维和毛细血管壁,各实验组表达均高于N组.术后1天T组比AT组表达显著增高(P＜0.01),术后3天AT组比T组表达增高(P＜0.05),术后14天AT组比T组表达显著增高(P＜0.01).结论:大鼠急性酒精中毒合并颅脑外伤后晚期,海马CA1区AQP4表达增高,可能加重晚期继发性脑水肿,是急性酒精中毒合并颅脑外伤预后不良的原因之一.