树突状细胞制备脑胶质瘤疫苗的体外研究

目的　通过体外实验探讨应用树突状细胞制备的肿瘤疫苗抗脑胶质瘤的作用机制。方法　培养大鼠树突状细胞,冻融法制备胶质瘤抗原,以肿瘤抗原致敏树突状细胞而制备胶质瘤疫苗。将实验动物分为4组,分别将胶质瘤疫苗、树突状细胞、生理盐水注入正常大鼠体内,到达预定时间取出大鼠脾脏,MTT法检测大鼠淋巴细胞活性。结果　1次输入胶质瘤疫苗的正常大鼠的淋巴细胞对肿瘤细胞的杀伤活性明显低于3次输入胶质瘤疫苗的正常大鼠;比较输入培养8d的树突状细胞和输入生理盐水的大鼠,其淋巴细胞对肿瘤细胞的杀伤活性无统计学差异。结论　应用树突状细胞制备胶质瘤疫苗可明显激活体内抗肿瘤免疫反应。     

负载胶质瘤抗原的树突状细胞激发T细胞功能的实验研究

目的 对胶质瘤可溶性抗原和凋亡细胞抗原两种不同的抗原制备的DC疫苗活性进行研究,比较两种疫苗激发CTL功能的效能差异.方法 对手术切除的人脑胶质瘤细胞进行原代培养,冻融法制备可溶性抗原,紫外线照射制备凋亡细胞抗原,并取该患者的外周血进行细胞培养诱导DC,与可溶性抗原、凋亡细胞抗原、自体肿瘤细胞致敏DC后,用三种疫苗及正常DC诱导的CTL在体外对培养的胶质瘤细胞进行体外杀伤实验,对培养结果 进行统计学处理.结果 可溶性抗原制备的DC疫苗活性最强,其诱导的CTL的杀伤率达到88%,其次是凋亡细胞组的DC疫苗,其诱导的CTL的杀伤率达到72%,2组差异无统计学意义(P＞0.05).与自体肿瘤细胞共同培养的DC组杀伤率为31%,正常DC组(即RPMI-1640 DC组)杀伤率为21%,2组之间同样无明显差异(P＞0.05),两实验组分别与两对照组对比,杀伤率则有显著差异(P＜0.01或P＜0.05).结论 DC在负载抗原后诱导CTL杀伤活性显著提高,而DC与肿瘤细胞一起培养对CTL杀伤活性无明显影响.     

脑胶质细胞瘤的免疫学治疗

在中枢神经之外给予脑胶质瘤抗原 ,同时诱导体内抗原递呈细胞大量生成 ,或者将在体外诱导分化而产生的大量抗原递呈细胞回输入体内 ,通过抗原递呈细胞将脑胶质瘤抗原递呈给T淋巴细胞 ,从而激发机体对脑胶质瘤的免疫杀伤活性。近年在应用肿瘤免疫方法治疗脑胶质瘤荷瘤动物的实验研究方面 ,取得了诱人的结果。本文就脑胶质瘤免疫治疗的可能性、原理及治疗时机等方面作一综述。     

热诱导凋亡胶质瘤细胞致敏树突状细胞疫苗的制备与鉴定

目的 制备热诱导凋亡胶质瘤细胞致敏树突状细胞疫苗,探讨其增强树突状细胞抗原递呈、诱导细胞毒性T淋巴细胞产生更强肿瘤细胞杀伤作用的机制.方法 采用改良Inaba法,在重组小鼠粒细胞巨噬细胞集落刺激因子(rmGM-CSF)和重组小鼠白细胞介素-4(rmIL-4)作用下,体外诱导扩增小鼠骨髓来源的树突状细胞,电子显微镜和流式细胞术检测其生物学特征;分别以不同加热温度处理U251细胞,制备凋亡U251细胞致敏树突状细胞疫苗,3H-TdR掺入法和MTT法检测T淋巴细胞增殖能力和活化细胞毒性T淋巴细胞杀伤率.结果 在rmGM-CSF和rmIL-4作用下,小鼠骨髓来源细胞体外培养6～7 d即可诱导出树突状细胞,经倒置相差显微镜和电子显微镜证实细胞表面呈典型树突状结构;流式细胞术检测证实其表达特异性表面标记物CD11c,同时表达功能相关性抗原CD80、CD86和MHCⅡ.倒置相差显微镜和流式细胞术确定热诱导U251细胞凋亡的最佳条件为:44℃处理3 h再常规培养12 h,凋亡U251细胞可更好地负载树突状细胞,负载的树突状细胞可以激发T淋巴细胞增殖,诱导活化细胞毒性T淋巴细胞具有更强的杀伤肿瘤细胞的能力.结论 在rmGM-CSF和rmIL-4作用下,经体外成功制备的小鼠骨髓来源的树突状细胞,可热诱导凋亡胶质瘤细胞敏敏树突状细胞疫苗于体外有效激发T淋巴细胞增殖,诱导细胞毒性T淋巴细胞产生较强的杀伤肿瘤细胞能力.     

肿瘤抗原致敏树突状细胞瘤苗治疗颅内胶质瘤的实验研究

目的　研究肿瘤抗原致敏树突状细胞瘤苗治疗胶质瘤的疗效。方法　从大鼠的骨髓中加入GM CSF和IL 4培养树突状细胞 ,采用相差显微镜、扫描电镜观察了树突状细胞的形态学特点 ;免疫组织化学双标技术、流式细胞免疫学技术观察了其特异性抗体OX6和OX62 的表达 ;微酸洗脱方法抽提C6肿瘤抗原体外致敏树突状细胞 ,建立C6胶质瘤脑内动物模型 ,体内应用抗原致敏的树突状细胞 ,观察脑内肿瘤的疗效 ,并取致敏的动物的脾脏T细胞体外加入C6肿瘤抗原 ,加入IL 2培养进行CTL活性检测。结果　培养第 8天可见有典型的树突状细胞 ;免疫组织化学双标可见有OX6和OX62 阳性细胞 ,流式细胞免疫学分析发现OX62 阳性率为 93 0 3% ,OX6的阳性率为 92 0 1% ;体外细胞毒试验发现对相应的C6肿瘤细胞有明显的杀伤作用 ;动物实验发现实验组可见肿瘤组织内有大量的坏死 ,而对照组仅有少量的坏死 ,两者相比P <0 0 1。结论　体内注射采用微酸洗脱的抗原肽致敏树突状细胞瘤苗能够引起荷瘤动物脑肿瘤大面积的坏死 ,该方法为将来临床免疫治疗胶质瘤充分调动机体的免疫系统奠定基础。     

树突状细胞活化的CTLs对神经胶质瘤的体外杀伤作用研究

目的研究负载肿瘤抗原的树突状细胞(DCs)活化的特异性细胞毒性T淋巴细胞(CTLs)对神经胶质瘤细胞的体外杀伤效应,探讨其用于临床治疗的可行性。方法体外原代培养胶质瘤细胞,冻融法获取胶质瘤细胞抗原,联合应用粒细胞/巨噬细胞集落刺激因子、白细胞介素-4和肿瘤坏死因子-α等,对人外周血单核细胞进行体外诱导来获取DCs并负载肿瘤抗原,激活自体T淋巴细胞,制备特异性CTLs,MTT法检测对胶质瘤细胞的体外杀伤效应。结果负载胶质瘤抗原的DCs激活的CTLs对胶质瘤的杀伤作用显著高于对K562细胞的杀伤作用(P<0.01),并且杀伤活性随着效靶比的增加而增加;负载胶质瘤抗原的DCs激活的CTLs对胶质瘤的杀伤活性明显高于未经胶质瘤抗原致敏的DCs刺激的CTLs对胶质瘤的杀伤作用(P<0.01)。结论联合应用细胞因子从人外周血中诱导出的DCs负载胶质瘤抗原后,激活的CTLs在体外对胶质瘤细胞能产生高效而特异的杀伤作用,为临床应用DCs瘤苗奠定基础。     

树突状细胞治疗脑胶质细胞瘤实验研究

目的研究树突状细胞疫苗瘤内注射对胶质瘤的治疗作用.方法建立大鼠C6脑胶质瘤皮下和颅内肿瘤模型,通过第一组为瘤内注射树突状细胞(DC)、第二组为腹部皮下注射DC、第三组为对照组,观察肿瘤生长情况和大鼠生存时间,比较细胞毒性T淋巴细胞(CTL)的活性,并进行病理学检查.结果治疗组大鼠表现为肿瘤生长部分抑制,生存时间明显延长,与对照组比较,有极显著差异(P<0.01),瘤内注射DC和腹部皮下注射C6冻融抗原致敏DC,两治疗组间无显著性差异(P＝0.60);CTL杀伤活性增强,和对照组比较有显著性差异(P<0.05).双侧皮下种植的肿瘤治疗一侧后,生长均受到抑制,并逐渐缩小.结论瘤内注射DC治疗脑胶质瘤是一种新的、有效的免疫治疗策略.     

树突状细胞的培养及其诱导的神经胶质瘤体外杀伤作用研究

目的　研究负载肿瘤抗原的树突状细胞 (DCs)活化的特异性细胞毒性T淋巴细胞 (CTLs)对神经胶质瘤细胞的体外杀伤效应 ,探讨其用于临床治疗的可行性。方法　体外原代培养 12例胶质瘤细胞 ,冻融法获取胶质瘤细胞抗原 ,联合应用粒细胞 /巨噬细胞集落刺激因子、白细胞介素 4和肿瘤坏死因子 α等 ,对人外周血单核细胞进行体外诱导来获取DCs并负载肿瘤抗原 ,激活自体T淋巴细胞 ,制备特异性CTLs,MTT法检测对胶质瘤细胞的体外杀伤效应。结果　负载胶质瘤抗原的DCs激活的CTLs对胶质瘤细胞有明显的杀伤作用 ,显著高于K5 6 2细胞对照组 ,并且杀伤率随着效靶比的增加而增加。结论　从人外周血中诱导的DCs负载胶质瘤抗原后 ,激活的CTLs在体外对胶质瘤能产生高效的杀伤作用 ,为临床应用DCs瘤苗奠定基础     

脑胶质瘤特异性肿瘤疫苗的制备

目的 探讨运用树突状细胞和肿瘤组织匀浆制成的特异性肿瘤疫苗(DC肿瘤疫苗)治疗脑胶质瘤的新途径。方 法抽取脑胶质瘤患外周血50ml，体外培养扩增树突状细胞，再利用患术中取出的肿瘤细胞裂解物体外致敏树突状细胞制成DC肿瘤疫苗，静脉回输病人体内。结果 经临床41例120次的DC疫苗治疗，无一例发生不良反应和其他副作用，安全系数大。结论 运用DC和肿瘤组织匀浆制备肿瘤疫苗安全有效，具有临床应用前景。．     

凋亡肿瘤细胞抗原致敏的树突状细胞瘤苗治疗大鼠颅内胶质瘤的实验研究

目的观察凋亡肿瘤细胞抗原致敏的树突状细胞(dendriticcell,DC)瘤苗对颅内胶质瘤免疫治疗的效果。方法通过立体定向接种建立Wistar大鼠C6胶质瘤动物模型;从大鼠骨髓分离DC前体细胞,经重组大鼠粒细胞巨噬细胞集落刺激因子(rrGM-CSF) 白细胞介素4(rrIL-4)诱导培养、扩增获得功能性DCs;DCs经采用热诱导凋亡的C6胶质瘤细胞体外致敏后皮下回输荷瘤大鼠体内,1次/周,共5次。观察荷瘤大鼠的存活期,MRI观察颅内肿瘤生长情况,循环血中CD8 T淋巴细胞水平及体外细胞毒反应、增殖反应均以流式细胞仪检测。结果经过治疗的荷瘤大鼠生存期明显延长,MRI显示实验组大鼠肿瘤被明显抑制,外周血中CD8 T淋巴细胞比例增加,体外细胞毒试验提示经凋亡肿瘤细胞抗原致敏的DC瘤苗可以诱导针对C6胶质瘤的特异性细胞毒性T淋巴细胞,并且未观察到自身免疫反应的发生。结论经凋亡肿瘤细胞抗原致敏的DC瘤苗对于颅内胶质瘤是一种安全有效的治疗方法。     

Immunotherapy of rat glioma without accumulation of CD4~+CD25~+FOXP3~+ regulatory T cells

Immunotherapy may be used for the treatment of glioblastoma multiforme;however,the induced immune response is inadequate when either T cells or dendritic cells are used alone.In this study,we established a novel vaccine procedure in rats,using dendritic cells pulsed with C6 tumor cell lysates in combination with adoptive transfer of T lymphocytes from syngenic donors.On day 21 after tumor inoculation,all the rats were sacrificed,the brains were harvested for calculation of glioma volume,cytolytic T lymphocyte responses were measured by cytotoxic assay,and the frequency of regulatory T lymphocytes(CD4+CD25+FOXP3+) in the peripheral blood was investigated by flow cytometric analysis.The survival rate of rats bearing C6 glioma was observed.Results showed that the co-immunization strategy had significant anti-tumor potential against the pre-established C6 glioma,and induced a strong cytolytic T lymphocyte response in rats.The frequency of peripheral blood CD4+CD25+FOXP3+ regulatory T lymphocytes was significantly decreased following the combination therapy,and the rats survived for a longer period.Experimental findings indicate that the combined immunotherapy of glioma cell lysate-pulsed dendritic cell vaccination following adoptive transfer of T cells can effectively inhibit the growth of gliomas in rats,boost anti-tumor immunity and produce a sustained immune response while avoiding the accumulation of CD4+CD25+FOXP3+ regulatory T lymphocytes.     

Lymphokine activateed killer (LAK) cell-mediated lysis of murine glioma: trypsinchymotrypsin-sensitive glioma protein is responsible for tumor-selective recognition by LAK cells

The killing of Fischer rat 9L glioma in vitro by lymphokine-activated killer (LAK) cells was studied. LAK cells generated by culturing Fischer spleen cells with recombinant interleukin 2 markedly lysed glioma cells but did not kill syngeneic normal brain tissue in a chromium release microcytotoxicity assay. Susceptibility of glioma to lysis by LAK cells was markedly diminished by pretreating the glioma cells with trypsin or chymotrypsin but was unaffected by pretreatment with neuraminidase, glycosidases, or sodium periodate. These results suggest that LAK cell killing of glioma is probably tumor-selective and that a crucial cell surface determinant on glioma cells responsible for its tumot-selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.     

骨髓间充质干细胞向脑胶质瘤趋向性的初步研究

背景骨髓间充质干细胞(MSCs)是存在于骨髓中的非造血类干细胞,具有自我更新及多向分化潜能.在大鼠脑外伤模型中的迁移能力已得到证实,而其对于脑胶质瘤的趋向性的研究尚处于初期.本实验通过将标记的MSCs移植到大鼠脑胶质瘤模型体内,观察它的迁移情况.方法采用全骨髓细胞培养法,利用MSCs的贴壁生长及可在体外长期培养的特性,获取纯化的MSCs.采用流式细胞术鉴定其表面抗原及细胞周期.在处于对数生长期的MSCs培养皿中加入BrdUrd(终浓度10μg/mL),培养24～48 h后进行移植.采用立体定向技术建立大鼠脑胶质瘤模型,3 d后移植标记好的MSCs在大脑半球组,BrdUrd标记的MSCs被注入大鼠脑胶质瘤模型肿瘤对侧大脑;在颈内动脉组,BrdUrd标记的MSCs被注入大鼠脑胶质瘤模型肿瘤同侧的颈内动脉.分别以BrdUrd标记的3T3细胞作为对照组.2周后,处死大鼠取脑组织制作病理切片,进行抗BrdUrd免疫组化及免疫荧光染色,观察MSCs的迁移情况.结果全骨髓培养法获得了纯化的MSCs.移植到脑组织及颈内动脉的BrdUrd标记的MSCs表现出了明显的向脑胶质瘤迁移的特性.在大脑半球组,MSCs主要集中在肿瘤与正常脑组织的交界部位,在瘤内只有少量分布.在颈内动脉组,MSCs主要分布于肿瘤内部,在肿瘤与正常脑组织的交界位置有少量分布.结论MSCs具有明显的向脑胶质瘤迁移的特性,同时亦可通过血脑屏障,有可能成为胶质瘤基因治疗的理想载体.     

大鼠树突状细胞疫苗治疗脑胶质瘤的实验研究

目的研究树突状细胞疫苗对C6荷瘤大鼠的免疫治疗效应,并比较免疫治疗策略的异同。方法将成年健康SD大鼠40只平均分为4组,分别经RN A致敏和C6冻融抗原致敏的DC免疫以及对照组经未致敏D C和R PM I1640免疫,采用LD H试剂盒检测CTL的体外杀伤活性。建立大鼠C6脑胶质瘤颅内肿瘤模型,观察其生存期,并进行病理学检查。结果肿瘤RN A致敏的D C疫苗活性最强,与C6冻融抗原致敏的DC疫苗相比,CTL杀伤活性差异不显著(P>0.05),但与对照组相比,差异非常显著(P<0.01)。治疗组荷瘤大鼠生存时间与对照组相比,差异非常显著(P<0.01);两治疗组之间差异不显著(P>0.05)。治疗组肿瘤生长明显抑制。结论C6冻融抗原和肿瘤细胞R NA致敏的树突状细胞疫苗均是有效的免疫治疗方法。     

GABAergic mechanisms of the lateral parabrachial nucleus on sodium appetite

GABAergic activation in the lateral parabrachial nucleus (LPBN) induces sodium and water intake in satiated and normovolemic rats. In the present study we investigated the effects of GABAA receptor activation in the LPBN on 0.3M NaCl, water, 2% sucrose and food intake in rats submitted to sodium depletion (treatment with the diuretic furosemide subcutaneously+sodium deficient food for 24h), 24h food deprivation or 24 h water deprivation. Male Holtzman rats with bilateral stainless steel cannulas implanted into the LPBN were used. In sodium depleted rats, muscimol (GABAA receptor agonist, 0.5 nmol/0.2 microl), bilaterally injected into the LPBN, produced an inconsistent increase of water intake and two opposite effects on 0.3M NaCl intake: an early inhibition (4.3+/-2.7 versus saline: 14.4+/-1.0 ml/15 min) and a late facilitation (37.6+/-2.7 versus saline: 21.1+/-0.9 ml/180 min). The pretreatment of the LPBN with bicuculline (GABAA receptor antagonist, 1.6 nmol) abolished these effects of muscimol. Muscimol into the LPBN also reduced food deprivation-induced food intake in the first 30 min of test (1.7+/-0.6g versus saline: 4.1+/-0.6g), without changing water deprivation-induced water intake or 2% sucrose intake in sodium depleted rats. Therefore, although GABAA receptors in the LPBN are not tonically involved in the control of sodium depletion-induced sodium intake, GABAA receptor activation in the LPBN produces an early inhibition and a late facilitation of sodium depletion-induced sodium intake. GABAA activation in the LPBN also inhibits food intake, while it consistently increases only sodium intake and not water, food or sucrose intake.     

The effects of osmotic stimulation and water availability on c-Fos and FosB staining in the supraoptic and paraventricular nuclei of the hypothalamus

We studied the effects of osmotic stimulation on the expression of FosB and c-Fos in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). Adult male rats were divided into two groups that were injected with lidocaine (0.1-0.2 ml sc) followed by either 0.9% or 6% NaCl (1 ml/100 g bw sc). After the NaCl injections, the rats were anesthetized and perfused 2, 6, or 8 h after the injections. Their brains were prepared for immunocytochemistry and stained with FosB and c-Fos antibodies. The number of c-Fos-positive cells was significantly increased only at 2 h in the SON and PVN. In contrast, the number of FosB-positive cells was significantly increased at 6, and 8 h in both the SON and PVN. In a second experiment, the effect of water availability on FosB staining 8 h after injections of 6% NaCl was tested in 3 groups of rats: water ad libitum, rats that had no access to water, and rats that were given water 2 h prior to perfusion. FosB staining was significantly reduced in both the SON and the PVN of rats that had ad libitum water compared to the two water-restricted groups. In the third experiment, rats were injected with either 0.9% NaCl or 6% NaCl and were either given ad libitum access to water or water restricted for 6 h after the injections and perfused 24 h after the saline injections. FosB staining was not increased when water was available ad libitum. FosB staining was significantly increased at 24 h in the rats injected with 6% NaCl when water was restricted. Thus, FosB may continue to influence protein expression in the SON and PVN for at least 24 h following acute osmotic stimulation.     

Prolonged survival of rats with intracranial C6 gliomas by treatment wit~ TGF-β antisense gene

Abstract

Using an intracranial rat C6 glioma model, we tested the hypothesis that gene modification ofglioma cells to block the expression of the immunosuppressive cytokine TGF-[3 (transforming growth factor (3) may enhance anti-tumor immune responses and thereby prolong survival of tumor-bearing animals. The cDNA for simian TGF-β2 was ligated in antisense orientation into the episomal plasmid mammalian expression vector pCEP-4. This TGF-β-antisense vector was transfected into C6 glioma cells by standard electroporation techniques. PCR was used to determine that the rat C6 clones were successfully transfected with the antisense-TGFβ construct. Twenty-nine adult female Wistar rats harboring 7-day-old intracranial C6 tumors were then subcutaneously injected with either saline (n = 9), unmodified C6 glioma cells (n =10), or TGF-β-antisense-modified C6 cells (n =70). Animals were followed, for survival, and Fisher!s exact method was used to interpret the significance of differences between experimental groups. The survival of tumor-bearing rats injected with TGF-β-antisense-modified C6 cells was significantly prolonged! relative to the survival of rats receiving injections of saline or unmodified C6 cells alone. Six of the ten (60%) TGF-β-antisense treated animals survived for 72 weeks! whereas none of the nine (0%) animals treated with saline and none of ten (0%) of those treated with C6 cells alone survived past 5 weeks. These results indicate that the genetic inhibition of immunosuppressive cytokines (such as TGF-(3) may reverse the phenotypic immunosuppression caused by such factors, and thereby prolong the survival of C6 tumorbearing animals. Future investigations using cytokine gene modifications in other brain tumor models are warranted. [Neural Res 1998; 20: 742–747]     

The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma

We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats

The effects of postweaning social isolation (pwSI) on the morphology of the pyramidal neurons from the medial part of the prefrontal cortex (mPFC) and hippocampus were investigated in rats. The animals were weaned on day 21 postnatal (P21) and isolated 8 weeks. After the isolation period, locomotor activity was evaluated through 60 min in the locomotor activity chambers and the animals were sacrificed by overdoses of sodium pentobarbital and perfused intracardially with 0.9% saline solution. The brains were removed, processed by the Golgi-Cox stain and analyzed by the Sholl method. The locomotor activity in the novel environment from the isolated rats was increased with respect to the controls. The dendritic morphology clearly showed that the pwSI animals presented a decrease in dendritic length of pyramidal cells from the CA1 of the hippocampus without changes in the pyramidal neurons of the mPFC. However, the density of dendritic spines was decreased in the pyramidal cells from mPFC and Hippocampus. In addition, the Sholl analyses showed that pwSI produced a decrease in the number of sholl intersections compared with the control group only in the hippocampus region. The present results suggest that pwSI may in part affect the dendritic morphology in the limbic structures such as mPFC and hippocampus that are implicated in schizophrenia.